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Zhang Y, Wu Y, Pei B, Sun Q, Zhang C, Yang Q, Jin Y, Wu J, Li X. Piwei Peiyuan Prescription Attenuates the Progression of Chronic Atrophic Gastritis by Eliciting MAPK10-Mediated Mitochondrial Autophagy. Cell Biol Int 2025; 49:692-708. [PMID: 40103313 DOI: 10.1002/cbin.70016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2024] [Revised: 02/25/2025] [Accepted: 02/28/2025] [Indexed: 03/20/2025]
Abstract
Piwei Peiyuan (PWPY) prescription is a traditional Chinese medicine prescription and has been efficiently used in the clinics to treat chronic atrophic gastritis (CAG) for many years. However, the mechanism of action underlying PWPY for treating CAG remains elusive. A CAG rat animal and cell model was constructed in this study to explore the action mechanism of PWPY prescription in treating CAG. Here we show that PWPY attenuates the progression of CAG by eliciting MAPK10-mediated mitochondrial autophagy. Experimental model of CAG was introduced using N-methyl-n'-nitro-n-nitroguanidine (MNNG). Our histological analyses reveal that MNNG-induced CAG in rat undergoes classical morphological alterations judged by immunohistochemistry and serum level of PGⅠ, PGⅡ, and G17. Importantly, PWPY treatment prevents the progression of MNNG-induced CAG judged by serum level of PGⅠ, PGⅡ, and G17. Interestingly, PWPY treatment inhibits MAPK10 activity judged by biochemical assays and promotes mitochondrial autophagy judged by electron microscopic analyses. Thus, we conclude that PWPY attenuates the progression of MNNG-induced CAG and prevents precancerous lesions by harnessing MAPK10-elicited mitochondrial autophagy. The MNNG-induced experimental CAG model provides a robust platform for further delineating therapeutic targets underlying PWPY regimen.
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Affiliation(s)
- Yi Zhang
- The Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, Anhui, China
| | - Ying Wu
- The Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, Anhui, China
| | - Bei Pei
- The Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, Anhui, China
| | - Qin Sun
- The Department of Spleen and Stomach, Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, Anhui, China
| | - Cheng Zhang
- The Research Department, Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, Anhui, China
| | - Qi Yang
- The Department of Spleen and Stomach, Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, Anhui, China
| | - Yueping Jin
- The Department of Spleen and Stomach, Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, Anhui, China
| | - Jing Wu
- The Department of Spleen and Stomach, Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, Anhui, China
| | - Xuejun Li
- The Department of Spleen and Stomach, Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, Anhui, China
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Zhang H, Xiong P, Zheng T, Hu Y, Guo P, Shen T, Zhou X. Combination of Berberine and Evodiamine Alleviates Obesity by Promoting Browning in 3T3-L1 Cells and High-Fat Diet-Induced Mice. Int J Mol Sci 2025; 26:4170. [PMID: 40362407 PMCID: PMC12072149 DOI: 10.3390/ijms26094170] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2025] [Revised: 04/13/2025] [Accepted: 04/24/2025] [Indexed: 05/15/2025] Open
Abstract
Traditional Chinese medicine has long acknowledged the therapeutic potential of Tetradium ruticarpum (A.Juss.) T.G.Hartley together with Coptis chinensis Franch in managing metabolic disorders. However, their combined anti-obesity effects and the underlying mechanisms remain poorly characterized. This study investigates the synergistic anti-obesity effects and mechanisms of a combined berberine and evodiamine treatment (BBE) in high-fat diet (HFD)-induced C57BL/6J mice and 3T3-L1 cells. In vitro, cell viability was evaluated using the Cell Counting Kit-8 (CCK-8), while lipid accumulation was assessed through Oil Red O staining and triglyceride content determination. Molecular docking simulations performed with AutoDockTools 1.5.6 software Vina predicted interactions between BBE and key proteins. The analysis of genes and proteins involved in browning and thermogenesis was conducted using quantitative reverse transcription polymerase chain reaction and Western blotting. In vivo, HFD-induced mice were assessed for serum lipids profiles, glucose, insulin, adipocytokines, fat tissue morphology (Hematoxylin and eosin staining), mitochondrial activity (flow cytometry), and protein expression (immunofluorescence). Molecular docking analysis revealed strong binding affinities between BBE and key target proteins, including UCP1, PGC-1α, PRDM16, CIDEA, FGF21, and FGFR1c. BBE significantly reduced lipid accumulation in 3T3-L1 cells, upregulated the mRNA expression of Prdm16, Cidea, Ucp1, and Dio2, elevated UCP1 and PGC-1α protein levels, and activated the FGF21/PGC-1α signaling pathway. In HFD-induced mice, BBE administration led to reduced body weight, smaller adipocyte size, increased adipocyte number, and alleviated hepatic steatosis. Furthermore, it lowered serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and levels of triglycerides (TG), while simultaneously increasing concentrations of high-density lipoprotein cholesterol (HDL-C). BBE also improved glucose tolerance, reduced fasting insulin levels, and modulated adipocytokine levels (reduced leptin, increased adiponectin), while promoting browning gene and protein expression. Overall, the combination of berberine and evodiamine mitigates obesity by enhancing browning and activating the FGF21/PGC-1α signaling pathway.
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Affiliation(s)
| | | | | | | | | | | | - Xin Zhou
- School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; (H.Z.); (P.X.); (T.Z.); (Y.H.); (P.G.); (T.S.)
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Zheng J, Jiao Z, Yang X, Ruan Q, Huang Y, Jin C, Gui S, Xuan Z, Jia X. Network pharmacology-based exploration of the mechanism of Wenweishu granule in treating chronic atrophic gastritis with spleen-stomach cold deficiency syndrome. JOURNAL OF ETHNOPHARMACOLOGY 2025; 345:119591. [PMID: 40054637 DOI: 10.1016/j.jep.2025.119591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Revised: 02/14/2025] [Accepted: 03/05/2025] [Indexed: 03/17/2025]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Wenweishu (WWS) is a traditional Chinese medicine compound formulated for chronic atrophic gastritis (CAG) treatment by warming the stomach and alleviating pain. However, its pharmacological mechanisms remain underexplored. AIM OF THE STUDY This study investigated the therapeutic effects and potential mechanisms of WWS on CAG with spleen-stomach cold deficiency syndrome (SSCDS). METHODS To achieve this, an SSCDS-CAG rat model and a human gastric mucosal epithelial cells (GES-1) cell model were established using multi-factor modeling and N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG) induction, respectively. WWS's effects on gastric injury were evaluated through pathology, inflammation, serum biomarkers, and apoptosis. Additionally, MNNG's effects on GES-1 cells were analyzed. Network pharmacology, involving protein-protein interaction networks, GO/KEGG enrichment, and molecular docking, was employed to predict WWS's potential targets and mechanisms in SSCDS-CAG. Mechanistic insights were further validated using immunohistochemistry, quantitative reverse transcription polymerase chain reaction, and western blotting. RESULTS In vivo results showed that WWS alleviated symptoms in SSCDS-CAG rats, lowering symptom scores and improving gastric histopathology. It modulated serum biomarkers and reduced inflammation and apoptosis in both in vivo and in vitro studies. Network pharmacology results revealed 263 overlapping targets between WWS and SSCDS-CAG, associated with apoptosis, inflammation, and the PI3K/AKT pathway. Molecular docking revealed strong binding affinity between the core target and active WWS components. In SSCDS-CAG rats and GES-1 cells, WWS inhibited PI3K/AKT phosphorylation, increased PTEN expression, and regulated Bcl-2, Bax, and cleaved caspase-3 levels. CONCLUSION WWS reduces inflammation and apoptosis in multi-factor CAG rats and MNNG-induced GES-1 cells by modulating the PTEN/PI3K/AKT signaling pathway and apoptosis-related proteins.
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Affiliation(s)
- Jia Zheng
- College of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, China; Anhui Province Key Laboratory of Bioactive Natural Products, Hefei, 230012, China
| | - Zhiyong Jiao
- College of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, China; Anhui Province Key Laboratory of Bioactive Natural Products, Hefei, 230012, China
| | - Xinyu Yang
- College of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, China; Anhui Province Key Laboratory of Bioactive Natural Products, Hefei, 230012, China
| | - Qing Ruan
- College of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, China; Anhui Province Key Laboratory of Bioactive Natural Products, Hefei, 230012, China
| | - Yuzhe Huang
- College of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, China; Institute of Pharmaceutics, Anhui Academy of Chinese Medicine, Hefei, Anhui, 230012, China
| | - Cheng Jin
- College of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, China; Institute of Pharmaceutics, Anhui Academy of Chinese Medicine, Hefei, Anhui, 230012, China
| | - Shuangying Gui
- College of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, China; Institute of Pharmaceutics, Anhui Academy of Chinese Medicine, Hefei, Anhui, 230012, China
| | - Zihua Xuan
- College of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, China; Anhui Province Key Laboratory of Bioactive Natural Products, Hefei, 230012, China
| | - Xiaoyi Jia
- College of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, China; Anhui Province Key Laboratory of Bioactive Natural Products, Hefei, 230012, China.
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Li JM, Song ZH, Li Y, Chen HW, Li H, Yuan L, Li J, Lv WY, Liu L, Wang N. NR4A1 silencing alleviates high-glucose-stimulated HK-2 cells pyroptosis and fibrosis via hindering NLRP3 activation and PI3K/AKT pathway. World J Diabetes 2025; 16:97544. [PMID: 40093286 PMCID: PMC11885978 DOI: 10.4239/wjd.v16.i3.97544] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2024] [Revised: 10/15/2024] [Accepted: 12/16/2024] [Indexed: 01/21/2025] Open
Abstract
BACKGROUND The pathophysiology of diabetic kidney disease (DKD) is complex. Interfering with the processes of pyroptosis and fibrosis is an effective strategy for slowing DKD progression. Previous studies have revealed that nuclear receptor subfamily 4 group A member 1 (NR4A1) may serve as a novel pathogenic element in DKD; however, the specific mechanism by which it contributes to pyroptosis and fibrosis in DKD is unknown. AIM To investigate the role of NR4A1 in renal pyroptosis and fibrosis in DKD and possible molecular mechanisms. METHODS Streptozotocin 60 mg/kg was injected intraperitoneally to establish a rat model of DKD. Typically, 45 mmol/L glucose [high glucose (HG)] was used to activate HK-2 cells to mimic the DKD model in vitro. HK-2 cells were transfected with NR4A1 siRNA to silence NR4A1. RESULTS NR4A1 was elevated in renal tissues of DKD rats and HG-stimulated HK-2 cells. Concurrently, NOD-like receptor protein 3 (NLRP3) and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathways were triggered, and pyroptosis and expression of fibrosis-linked elements was increased in vivo and in vitro. These alterations were significantly reversed via NR4A1 silencing. CONCLUSION Inhibition of NR4A1 mitigated pyroptosis and fibrosis via suppressing NLRP3 activation and the PI3K/AKT pathway in HG-activated HK-2 cells.
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Affiliation(s)
- Jin-Meng Li
- Department of Clinical Medicine, Jining Medical University, Jining 272013, Shandong Province, China
| | - Zi-Hua Song
- Department of General Medicine, Affiliated Hospital of Jining Medical University, Jining 272029, Shandong Province, China
| | - Yuan Li
- Department of General Medicine, Affiliated Hospital of Jining Medical University, Jining 272029, Shandong Province, China
| | - Han-Wen Chen
- Department of General Medicine, Affiliated Hospital of Jining Medical University, Jining 272029, Shandong Province, China
| | - Han Li
- Department of General Medicine, Affiliated Hospital of Jining Medical University, Jining 272029, Shandong Province, China
| | - Lu Yuan
- Department of Clinical Medicine, Jining Medical University, Jining 272013, Shandong Province, China
| | - Jing Li
- Department of Clinical Medicine, Jining Medical University, Jining 272013, Shandong Province, China
| | - Wen-Yue Lv
- Department of Clinical Medicine, Jining Medical University, Jining 272013, Shandong Province, China
| | - Lei Liu
- Department of General Medicine, Affiliated Hospital of Jining Medical University, Jining 272029, Shandong Province, China
| | - Na Wang
- Department of General Medicine, Affiliated Hospital of Jining Medical University, Jining 272029, Shandong Province, China
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Wang L, Lian YJ, Dong JS, Liu MK, Liu HL, Cao ZM, Wang QN, Lyu WL, Bai YN. Traditional Chinese medicine for chronic atrophic gastritis: Efficacy, mechanisms and targets. World J Gastroenterol 2025; 31:102053. [PMID: 40061592 PMCID: PMC11886037 DOI: 10.3748/wjg.v31.i9.102053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Revised: 12/06/2024] [Accepted: 01/21/2025] [Indexed: 02/18/2025] Open
Abstract
Chronic atrophic gastritis (CAG) is an important stage of precancerous lesions of gastric cancer. Effective treatment and regulation of CAG are essential to prevent its progression to malignancy. Traditional Chinese medicine (TCM) has shown multi-targeted efficacy in CAG treatment, with advantages in enhancing gastric mucosal barrier defense, improving microcirculation, modulating inflammatory and immune responses, and promoting lesion healing, etc. Clinical studies and meta-analyses indicate that TCM provides significant benefits, with specific Chinese herbal compounds and monomers demonstrating protective effects on the gastric mucosa through mechanisms including anti-inflammation, anti-oxidation, and regulation of cellular proliferation and apoptosis, etc. Finally, it is pointed out that the efficacy of TCM in the treatment of CAG requires standardized research and unified standards, and constantly clarifies and improves the evaluation criteria of each dimension of gastric mucosal barrier function.
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Affiliation(s)
- Li Wang
- Department of Gastroenterology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Yan-Jie Lian
- Division of Cardiovascular, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, China
| | - Jin-Sheng Dong
- Department of Gastroenterology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Ming-Kun Liu
- Department of Gastroenterology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Hong-Liang Liu
- Department of Gastroenterology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Zheng-Min Cao
- Department of Infectious Diseases, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Qing-Nan Wang
- Department of Dermatology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Wen-Liang Lyu
- Department of Infectious Diseases, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Yu-Ning Bai
- Department of Gastroenterology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
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Danielewski M, Zielińska S, Merwid-Ląd A, Szandruk-Bender M, Słupski W, Włodarczyk M, Sozański T, Ziółkowski P, Szeląg A, Nowak B. Sanguinarine-Chelerythrine from Coptis chinensis Offers Analgesic and Anti-Inflammatory Effects Without Gastrotoxicity. Pharmaceutics 2025; 17:323. [PMID: 40142987 PMCID: PMC11946437 DOI: 10.3390/pharmaceutics17030323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2024] [Revised: 01/30/2025] [Accepted: 02/26/2025] [Indexed: 03/28/2025] Open
Abstract
Background: Pain is a major clinical and socioeconomic problem worldwide. The available therapies are not always effective and are often associated with the multiple adverse effects that reduce their clinical application. Natural compounds are an important group of pharmaceuticals that may be used in pain management. We aimed to investigate the analgesic activity of the sanguinarine-chelerythrine from Coptis chinensis. Methods: The analgesic and anti-inflammatory activity of the sanguinarine-chelerythrine fraction of C. chinensis extract (SC 5 and 10 mg/kg), sanguinarine (SAN 1 and 2 mg/kg) and chelerythrine (CHEL 4 and 8 mg/kg) was assessed in tail flick and formalin tests. A microscopic and macroscopic examination of stomach mucosae was performed. TNFα and MMP-9 levels were measured with ELISA kits. Results: Morphine (MORF), CHEL and SC prolongated the tail withdrawal latency, with comparable analgesic activity between MORF and CHEL 8 mg/kg. MORF, CHEL 8 mg/kg, and SAN 2 mg/kg ameliorated the pain reaction in the neurogenic phase of the formalin test. In the inflammatory phase of the formalin test, all tested substances exerted analgesic activity. SAN, CHEL and SC additionally reduced TNFα and MMP-9 secretion. Conclusions: Our results confirmed analgesic effects of CHEL and SC with CHEL analgesic activity comparable to MORF. All investigated substances exerted significant anti-inflammatory activity without concomitant gastrotoxicity.
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Affiliation(s)
- Maciej Danielewski
- Department of Pharmacology, Wroclaw Medical University, ul. J. Mikulicza-Radeckiego 2, 50-345 Wroclaw, Poland; (M.D.); (A.M.-L.); (M.S.-B.); (W.S.); (A.S.)
| | - Sylwia Zielińska
- Department of Pharmaceutical Biotechnology, Wroclaw Medical University, ul. Borowska 211, 50-556 Wroclaw, Poland;
| | - Anna Merwid-Ląd
- Department of Pharmacology, Wroclaw Medical University, ul. J. Mikulicza-Radeckiego 2, 50-345 Wroclaw, Poland; (M.D.); (A.M.-L.); (M.S.-B.); (W.S.); (A.S.)
| | - Marta Szandruk-Bender
- Department of Pharmacology, Wroclaw Medical University, ul. J. Mikulicza-Radeckiego 2, 50-345 Wroclaw, Poland; (M.D.); (A.M.-L.); (M.S.-B.); (W.S.); (A.S.)
| | - Wojciech Słupski
- Department of Pharmacology, Wroclaw Medical University, ul. J. Mikulicza-Radeckiego 2, 50-345 Wroclaw, Poland; (M.D.); (A.M.-L.); (M.S.-B.); (W.S.); (A.S.)
| | - Maciej Włodarczyk
- Department of Pharmacognosy and Herbal Medicines, Wroclaw Medical University, ul. Borowska 211A, 50-556 Wroclaw, Poland;
| | - Tomasz Sozański
- Department of Preclinical Sciences, Pharmacology and Medical Diagnostics, Faculty of Medicine, Wroclaw University of Science and Technology, Wybrzeze Wyspianskiego 27, 50-370 Wroclaw, Poland;
| | - Piotr Ziółkowski
- Department of Pathology, Wroclaw Medical University, ul. K. Marcinkowskiego 1, 50-368 Wroclaw, Poland;
| | - Adam Szeląg
- Department of Pharmacology, Wroclaw Medical University, ul. J. Mikulicza-Radeckiego 2, 50-345 Wroclaw, Poland; (M.D.); (A.M.-L.); (M.S.-B.); (W.S.); (A.S.)
| | - Beata Nowak
- Department of Pharmacology, Wroclaw Medical University, ul. J. Mikulicza-Radeckiego 2, 50-345 Wroclaw, Poland; (M.D.); (A.M.-L.); (M.S.-B.); (W.S.); (A.S.)
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Liao W, Wang J, Li Y. Natural products based on Correa's cascade for the treatment of gastric cancer trilogy: Current status and future perspective. J Pharm Anal 2025; 15:101075. [PMID: 39957902 PMCID: PMC11830317 DOI: 10.1016/j.jpha.2024.101075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Revised: 07/18/2024] [Accepted: 08/16/2024] [Indexed: 02/18/2025] Open
Abstract
Gastric carcinoma (GC) is a malignancy with multifactorial involvement, multicellular regulation, and multistage evolution. The classic Correa's cascade of intestinal GC specifies a trilogy of malignant transformation of the gastric mucosa, in which normal gastric mucosa gradually progresses from inactive or chronic active gastritis (Phase I) to gastric precancerous lesions (Phase II) and finally to GC (Phase III). Correa's cascade highlights the evolutionary pattern of GC and the importance of early intervention to prevent malignant transformation of the gastric mucosa. Intervening in early gastric mucosal lesions, i.e., Phase I and II, will be the key strategy to prevent and treat GC. Natural products (NPs) have been an important source for drug development due to abundant sources, tremendous safety, and multiple pharmacodynamic mechanisms. This review is the first to investigate and summarize the multi-step effects and regulatory mechanisms of NPs on the Correa's cascade in gastric carcinogenesis. In phase I, NPs modulate Helicobacter pylori urease activity, motility, adhesion, virulence factors, and drug resistance, thereby inhibiting H. pylori-induced gastric mucosal inflammation and oxidative stress, and facilitating ulcer healing. In Phase II, NPs modulate multiple pathways and mediators regulating gastric mucosal cell cycle, apoptosis, autophagy, and angiogenesis to reverse gastric precancerous lesions. In Phase III, NPs suppress cell proliferation, migration, invasion, angiogenesis, and cancer stem cells, induce apoptosis and autophagy, and enhance chemotherapeutic drug sensitivity for the treatment of GC. In contrast to existing work, we hope to uncover NPs with sequential therapeutic effects on multiple phases of GC development, providing new ideas for gastric cancer prevention, treatment, and drug development.
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Affiliation(s)
- Wenhao Liao
- Department of Nephrology, the Key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Chongqing Clinical Research Center of Kidney and Urology Diseases, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, 400037, China
| | - Jing Wang
- Department of Obstetrics and Gynecology, Chongqing Bishan Hospital of Traditional Chinese Medicine, Chongqing, 402760, China
| | - Yuchen Li
- Department of Laboratory Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, China
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Cui G, Wang M, Liu Z, Chang C, Wu Y, Li X, Sun Z. Investigating the therapeutic effects and potential mechanisms of Zuojin Pill in the treatment of gastroesophageal reflux disease. JOURNAL OF ETHNOPHARMACOLOGY 2025; 340:119230. [PMID: 39662861 DOI: 10.1016/j.jep.2024.119230] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/13/2024] [Revised: 11/25/2024] [Accepted: 12/08/2024] [Indexed: 12/13/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Zuojin Pill (ZJP), a traditional Chinese medicinal formula, is widely recognized for its diverse pharmacological properties in the management of gastrointestinal disorders. However, the precise mechanisms underlying its therapeutic effects in gastroesophageal reflux disease (GERD) remain inadequately understood. AIM OF THE STUDY This study aims to investigate the therapeutic effects of ZJP in GERD and to elucidate the molecular mechanisms involved. MATERIALS AND METHODS The chemical composition of ZJP was characterized using HPLC-Q-Exactive-MS. A rat model of GERD was established through esophagogastric anastomosis, and three different doses of ZJP were administered. Histological changes were assessed via hematoxylin-eosin (H&E) staining, while pro-inflammatory cytokines were quantified to evaluate the anti-inflammatory effects of ZJP. Network pharmacology combined with bioinformatics analysis was employed to predict potential therapeutic targets and signaling pathways of ZJP in GERD. Validation of the mechanisms was conducted through Western blotting, immunofluorescence (IF), transmission electron microscopy (TEM), and immunohistochemistry (IHC). RESULTS The results demonstrated that ZJP effectively alleviated pathological alterations and reduced pro-inflammatory cytokine levels in esophageal tissues of GERD rats. Western blotting and IF analysis of E-cadherin and claudin-1 confirmed that ZJP enhanced the integrity of the esophageal mucosal barrier. TEM imaging revealed that ZJP restored intercellular space (DIS), increased desmosome density, thereby protecting esophageal tissues from the detrimental effects of GERD. Furthermore, ZJP modulated macrophage polarization in the GERD rat model. Mechanistic investigations indicated that ZJP exerted its therapeutic effects by inhibiting MAPK/NF-κB signaling pathway activation and downregulating the expression of prostaglandin-endoperoxide synthase 2 (PTGS2) and matrix metalloproteinase 2 (MMP2), consistent with predictions from network pharmacology analysis. CONCLUSIONS This study provides comprehensive evidence for the therapeutic efficacy of ZJP in GERD, acting through modulation of inflammation, mucosal barrier integrity, and macrophage polarization. Additionally, ZJP downregulated PTGS2 and MMP2 expression and suppressed the activation of MAPK/NF-κB signaling pathways, underscoring its potential as a therapeutic intervention for GERD.
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Affiliation(s)
- Guoliang Cui
- School of Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
| | - Manli Wang
- The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
| | - Zhiting Liu
- Jinling Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
| | - Cheng Chang
- Jiangsu Provincial Hospital of Chinese medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 225200, China.
| | - Yuanyuan Wu
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
| | - Xiaoman Li
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
| | - Zhiguang Sun
- The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
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Yuan Z, Wang Y, Wang X, Du X, Li G, Luo L, Yao B, Zhang J, Zhao F, Liu D. The fruit of Rosa odorata sweet var. gigantea (Coll. et Hemsl.) Rehd. et Wils attenuates chronic atrophic gastritis induced by MNNG and its potential mechanism. JOURNAL OF ETHNOPHARMACOLOGY 2025; 337:118876. [PMID: 39362325 DOI: 10.1016/j.jep.2024.118876] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Revised: 09/23/2024] [Accepted: 09/30/2024] [Indexed: 10/05/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Rosa odorata Sweet var. gigantea (Coll. et Hemsl.) Rehd. et Wils is a commonly utilized traditional medicine among the Yi nationality, also known as "Gugongguo", for the treatment of gastrointestinal disorders. Previous studies have indicated that the extract of Rosa odorata sweet var. gigantea (FOE) fruit has demonstrated a protective effect on the stomach; however, its impact on chronic atrophic gastritis (CAG) with severe disease remains unknown. AIM OF THE STUDY This study aimed to investigate the impact of FOE on CAG and its underlying mechanisms both in vitro and in vivo. MATERIALS AND METHODS By employing Ultra Performance Liquid Chromatography/Quadrupole-Time of Flight Mass Spectrometry (UPLC-QTOF-MS/MS) and network pharmacology, the primary active compounds and action targets of FOE were identified. In vitro, the impact of FOE on CAG was investigated through scratch, migration, and invasion assays. Subsequently, guided by network pharmacology, EMT and TGF-β signaling pathway-related proteins were assessed using Western blot and immunofluorescence experiments. Additionally, an in vivo CAG rat model was established to validate the effects of FOE and confirm its mechanism of action through hematoxylin-eosin (H&E), immunohistochemistry, Western blot, as well as untargeted metabolomics analysis of rat serum. It was observed that FOE inhibited scratch healing abilities, migration, invasion capabilities, as well as the expression of EMT-related proteins (E-cadherin, N-cadherin, Snail, Vimentin) in CAG model cells (MC cells), providing initial evidence for its efficacy. RESULTS Through the analysis of UPLC-QTOF-MS/MS, a total of 51 major compounds were identified in the FOE. Subsequent network pharmacological analysis suggested that FOE may regulate Epithelial mesenchymal transition (EMT) through the transforming growth factor β (TGF-β) pathway. Furthermore, experimental verification demonstrated that FOE inhibited the protein expression of TGF-β1 and its downstream protein Smad2/3 in vitro. In vivo findings also indicated similar mechanisms in MC cells, suggesting a reversal of the CAG process and significant inhibition of EMT and TGF-β signaling pathways. Additionally, untargeted metabolomics of rat serum confirmed the therapeutic effect of FOE on CAG and predicted its potential involvement in the arachidonic acid metabolic pathway. CONCLUSION This study initially demonstrated that FOE effectively reverses the process of EMT through the TGF-β1/Smad2/3 signaling pathway, thereby providing a therapeutic benefit for CAG.
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Affiliation(s)
- Zhen Yuan
- School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, China.
| | - Yansheng Wang
- Tianjin Modern Innovation Chinese Medicine Technology Co., Ltd., Tianjin, 300380, China; National Key Laboratory of Modern Chinese Medicine Innovation and Manufacturing, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
| | - Xinrui Wang
- Tianjin Modern Innovation Chinese Medicine Technology Co., Ltd., Tianjin, 300380, China; National Key Laboratory of Modern Chinese Medicine Innovation and Manufacturing, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
| | - Xiqin Du
- Tianjin Modern Innovation Chinese Medicine Technology Co., Ltd., Tianjin, 300380, China; National Key Laboratory of Modern Chinese Medicine Innovation and Manufacturing, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
| | - Guotong Li
- Tianjin Modern Innovation Chinese Medicine Technology Co., Ltd., Tianjin, 300380, China; National Key Laboratory of Modern Chinese Medicine Innovation and Manufacturing, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
| | - Lifei Luo
- Tianjin Modern Innovation Chinese Medicine Technology Co., Ltd., Tianjin, 300380, China.
| | - Bin Yao
- Tianjin Modern Innovation Chinese Medicine Technology Co., Ltd., Tianjin, 300380, China; National Key Laboratory of Modern Chinese Medicine Innovation and Manufacturing, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
| | - Jingze Zhang
- Tianjin Modern Innovation Chinese Medicine Technology Co., Ltd., Tianjin, 300380, China; National Key Laboratory of Modern Chinese Medicine Innovation and Manufacturing, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
| | - Feng Zhao
- School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, China.
| | - Dailin Liu
- Tianjin Modern Innovation Chinese Medicine Technology Co., Ltd., Tianjin, 300380, China; Haihe Laboratory of Modern Chinese Medicine, Tianjin, 301617, China.
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Liu S, Zhang T, Fang L, Hu L, Yin X, Tang X. Integrative pharmacological analysis of modified Zuojin formula: Inhibiting the HIF-1α-mediated glycolytic pathway in chronic atrophic gastritis. JOURNAL OF ETHNOPHARMACOLOGY 2025; 339:119136. [PMID: 39577677 DOI: 10.1016/j.jep.2024.119136] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Revised: 11/17/2024] [Accepted: 11/18/2024] [Indexed: 11/24/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Zuojin formula (ZJF) is a well-known herbal medicine in Pharmacopoeia of China, which is widely used for gastritis. Modified Zuojin formula (MZJF) was adapted based on traditional Chinese medicine (TCM) theories concerning gastric atrophy and dysplasia, along with extensive clinical experience, has been clinically employed to treat chronic atrophic gastritis (CAG). However, the underlying mechanisms by which MZJF intervenes in CAG remain to be fully elucidated. AIM OF THE STUDY The aim of this study was to evaluate the effects of MZJF intervention in CAG and explore its potential mechanisms. METHODS Four induction factors were used to establish a CAG rat model. HE and AB-PAS staining was utilized to assess the effects of MZJF in the intervention of CAG. The stomach weight index and gastric acid pH was used to assess the overall state of stomach. ELISA was used to assess the gastric mucosal inflammatory response. Using transmission electron microscopy to observe chief cells and parietal cells, we evaluated the improvement of ultrastructure by MZJF. Through network pharmacology analysis, the possible regulatory mechanism of MZJF in CAG was preliminarily explored. Binding interactions between MZJF components and predicted targets were explored using molecular docking. Subsequently, quantitative real-time PCR (qRT-PCR), Western blot, biochemical analysis and TUNEL staining were applied to validate the effect of MZJF on predicted pathway. RESULTS MZJF treatment ameliorated gastric mucosal pathology, inflammation, cellular ultrastructural damage and PG levels, halted the exacerbation of CAG in rats, along with a reduction in stomach weight index and gastric acid pH. A total of 79 compounds in MZJF targeting 203 CAG-related molecules were identified through network pharmacology. Enrichment analysis of the core targets was focused on the hypoxia inducible factor-1α (HIF-1α) signaling pathway. Molecular docking results identified HIF-1α as stable binding targets for MZJF primary components. Subsequently, PCR, WB, and biochemical results showed that MZJF suppressed the gene and protein expression levels of HIF-1α and its downstream molecules including glycolytic enzymes and transporters, modulated glucose, pyruvic acid and lactate levels in gastric mucosal tissue. Moreover, MZJF induced apoptosis of gastric epithelial cells, as evidenced by the upregulation of cleaved caspase-3, Bax, Bax/Bcl-2 and TUNEL positive cells ratio. CONCLUSIONS MZJF suppressed the HIF-1α-mediated glycolytic pathway, and promoted cell apoptosis, thereby halting the malignant transformation of CAG. The study provides a valuable reference point for applying TCM in preventing and treating CAG.
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Affiliation(s)
- Shan Liu
- Postdoctoral Research Station of China Academy of Chinese Medical Sciences, Institute of Digestive Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China.
| | - Tai Zhang
- Peking University Traditional Chinese Medicine Clinical Medical School (Xiyuan), Peking University Health Science Center, Beijing, 100091, China; Peking University Health Science Center, Beijing, 100191, China.
| | - Lihui Fang
- Graduate School, Beijing University of Chinese Medicine, Beijing, 100029, China; Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, 100091, China.
| | - Lanshuo Hu
- Graduate School, Beijing University of Chinese Medicine, Beijing, 100029, China; Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, 100091, China.
| | - Xiaolan Yin
- Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, 100091, China; Department of Gastroenterology, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, 361005, China.
| | - Xudong Tang
- Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, 100091, China.
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Chen L, Wang X, Li J, Zhang L, Wu W, Wei S, Zou W, Zhao Y. Elucidation of the mechanism of berberine against gastric mucosa injury in a rat model with chronic atrophic gastritis based on a combined strategy of multi-omics and molecular biology. Front Pharmacol 2025; 15:1499753. [PMID: 39834822 PMCID: PMC11743660 DOI: 10.3389/fphar.2024.1499753] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2024] [Accepted: 12/13/2024] [Indexed: 01/22/2025] Open
Abstract
Background Berberine (BBR) is widely used to treat gastrointestinal diseases. However, the pharmacological mechanism of action of BBR in anti-chronic atrophic gastritis (CAG) remains unclear. This study aimed to investigate the mechanism of action of BBR in CAG by integration of molecular biology and multi-omics studies strategy. Methods The CAG model was established by alternating drinking water of 0.1% ammonia and 20 mmol/L sodium deoxycholate, accompanied by an irregular diet. Serum biochemical indices including PGI, PGII, GAS-17, IL-6, IL-1β, and TNF-α were analyzed. HE and AB-PAS staining were employed to assess pathological damage in gastric tissue. The underlying molecular mechanism of BBR in CAG treatment was explored via the integration of network pharmacology, transcriptomics, widely targeted metabolomics and intestinal flora analysis. Finally, relevant key targets and pathway were verified. Results The results showed that BBR exerted therapeutic effects in improving CAG via alleviating inflammation response, maintaining the gastric mucosal barrier's integrity and repairing gastric mucosal tissues. Network pharmacology showed that the treatment of CAG by BBR mainly involved in inflammatory response, apoptosis, angiogenesis and metabolic processes. Furthermore, 234 different expression genes were identified in the gastric tissue transcriptome, which were mainly involved in biological processes such as cell adhesion, angiogenesis, apoptosis, cell migration and lipids metabolism by regulating the MAPK signaling pathway. Metabolomics results showed that 125 differential metabolites were also identified, while the pathways were mainly involved in D-glutamine and D-glutamate metabolism, and tyrosine metabolism, etc. Integrating transcriptomics and metabolomics analyses indicated that BBR directly regulated Carnitine C3:0, LPC (0:0/20:3), L-Glutamic Acid and FFA (15:0) by acting on SLC25A20, PNLIPRP1, PLA2G4C, GSR, GFPT2, GCLM, CTPS1, ACSL1, ACOT4 and ACOT2. 16S rRNA sequencing revealed that BBR could restore the balance of gut microbiota dysbiosis by significantly regulating the relative abundance of unclassified_Muribaculaceae and Lactobacillus_johnsonii. Conclusion This study demonstrated that BBR alleviates CAG through the regulation of the MAPK signaling pathway, metabolic disorders and gut microbiota dysbiosis, thereby revealing the complex mechanism of BBR in relation to alleviating CAG from multiple levels and perspectives.
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Affiliation(s)
- Lisheng Chen
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Department of Pharmacy, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Xin Wang
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Department of Pharmacy, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Jianyu Li
- Department of Pharmacy, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Lijuan Zhang
- Department of Pharmacy, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Wenbin Wu
- Healthcare Office of the Service Bureau of Agency for Offices Administration of the Central Military Commission, Beijing, China
| | - Shizhang Wei
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wenjun Zou
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yanling Zhao
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Department of Pharmacy, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
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Zhang Z, Liu J, Wang Y, Zhang L, Zhou T, Huang Y, Zhu T. Toll-like Receptor 4 Signaling Mediates Gastritis and Gastric Cancer. Curr Mol Med 2025; 25:388-398. [PMID: 38204278 DOI: 10.2174/0115665240276139231206071742] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Revised: 10/02/2023] [Accepted: 10/25/2023] [Indexed: 01/12/2024]
Abstract
The stomach is a crucial digestive organ in the human body, highly susceptible to inflammation or pathogen invasion, which can lead to various gastric diseases, including gastric cancer. Toll-like receptors (TLRs) are the first line of defense against pathogen invasion. TLR4, a member of the TLRs family, recognizes pathogen and danger-related molecular patterns to induce inflammatory responses. Helicobacter pylori (H. pylori) is a significant factor in gastric health, and TLR4 recognizes H. pylori -LPS to trigger an inflammatory response. Downstream TLR4 signaling generates proinflammatory cytokines that initiate inflammation in the gastric mucosa. In addition, TLR4 gene polymorphisms can increase health risks. This study aims to investigate the contribution of TLR4 to the inflammatory response in gastric diseases and the relation between TLR4 and H. pylori, TLR4 gene polymorphisms, and how TLR4 affects gastric diseases' possible pathways to provide further insight for future prevention and clinical treatment strategies.
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Affiliation(s)
- Zepeng Zhang
- Department of pharmacy, Kunshan Hospital of Traditional Chinese Medicine, Suzhou, China
| | - Ju Liu
- Department of pharmacy, Kunshan Hospital of Traditional Chinese Medicine, Suzhou, China
| | - Yi Wang
- Department of pharmacy, Kunshan Hospital of Traditional Chinese Medicine, Suzhou, China
| | - Lei Zhang
- Department of pharmacy, Kunshan Hospital of Traditional Chinese Medicine, Suzhou, China
| | - Tong Zhou
- Department of pharmacy, Kunshan Hospital of Traditional Chinese Medicine, Suzhou, China
| | - Yu Huang
- Department of pharmacy, Kunshan Hospital of Traditional Chinese Medicine, Suzhou, China
| | - Tongtong Zhu
- Department of pharmacy, Kunshan Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou, China
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Liu S, Ji H, Zhang T, Huang J, Yin X, Zhang J, Wang P, Wang F, Tang X. Modified Zuojin pill alleviates gastric precancerous lesions by inhibiting glycolysis through the HIF-1α pathway. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2025; 136:156255. [PMID: 39603037 DOI: 10.1016/j.phymed.2024.156255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Revised: 11/01/2024] [Accepted: 11/11/2024] [Indexed: 11/29/2024]
Abstract
BACKGROUND Gastric precancerous lesions (GPL) typically originates from chronic gastritis (CG), and the changes in glycolysis mediated by the HIF-1α pathway during the progression from CG to GPL are unclear. Modified Zuojin pill (SQQT) is a traditional Chinese herbal formula used for treating GPL. However, the underlying mechanism has not been fully elucidated. PURPOSE To investigate the changes in glycolysis mediated by the HIF-1α pathway during the progression from CG to GPL and whether SQQT can alleviate GPL by attenuating glycolysis through the HIF-1α pathway. METHODS A rat model of GPL was established, and the changes of glycolysis mediated by the HIF-1α pathway during the progression from CG to GPL were detected in 12th, 18th, 24th, and 30th weeks. The therapeutic efficacy of SQQT was evaluated through pathological changes. In vitro, the GPL cell model (MC cell) originated from GES-1 cells intervened by MNNG. The effects of SQQT on glycolysis and the HIF-1α pathway were detected in vivo and in vitro. In vitro, HIF-1α overexpression was used to confirmed that SQQT attenuated glycolysis by targeting the HIF-1α pathway. RESULTS Our study revealed that glycolysis mediated by the HIF-1α pathway exhibited dynamic changes in the progression from CG to GPL, characterized by sequential activation, deactivation, and reactivation. SQQT ameliorated gastric mucosal pathology and inflammation in GPL rats. Mechanistic studies revealed that SQQT alleviated glycolysis by targeting the HIF-1α pathway, and improved abnormal cellular proliferation and apoptosis. Importantly, HIF-1α overexpression blocked the effect of SQQT on glycolysis. CONCLUSION In the progression from CG to GPL, the HIF-1α pathway-mediated glycolysis was characterized by sequential activation, deactivation, and reactivation. SQQT attenuated glycolysis by targeting the HIF-1α pathway and improved abnormal cellular proliferation and apoptosis in the gastric mucosa, thereby exerting therapeutic effects on GPL.
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Affiliation(s)
- Shan Liu
- Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing 100091, China.
| | - Haijie Ji
- Shanxi Province Academy of Traditional Chinese Medicine, Taiyuan 030012, China
| | - Tai Zhang
- Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing 100091, China; Peking University Traditional Chinese Medicine Clinical Medical School (Xiyuan), Peking University Health Science Center, Beijing 100091, China
| | - Jinke Huang
- Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing 100091, China
| | - Xiaolan Yin
- Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing 100091, China
| | - Jiaqi Zhang
- Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing 100091, China
| | - Ping Wang
- Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing 100091, China
| | - Fengyun Wang
- Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing 100091, China
| | - Xudong Tang
- Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing 100091, China.
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14
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Liang L, He C, Han X, Liu J, Yang L, Chang F, Zhang Y, Lin J. Zuojin Pill Alleviates Precancerous Lesions of Gastric Cancer by Modulating the MEK/ERK/c-Myc Pathway: An Integrated Approach of Network Pharmacology, Molecular Dynamics Simulation, and Experimental Validation. Drug Des Devel Ther 2024; 18:5905-5929. [PMID: 39679136 PMCID: PMC11646374 DOI: 10.2147/dddt.s487371] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Accepted: 11/21/2024] [Indexed: 12/17/2024] Open
Abstract
Background Precancerous lesions of gastric cancer (PLGC) represent critical stages in gastric cancer progression, with a high risk of malignancy. Current treatments, such as Helicobacter pylori eradication, show limited efficacy in reversing precancerous molecular changes. Zuojin Pill (ZJP), a traditional Chinese medicine, has demonstrated potential for treating digestive disorders and may offer a promising approach for PLGC intervention. Objective This study aims to investigate the therapeutic effects and mechanisms of ZJP in treating PLGC, focusing on its active components, target pathways, and molecular interactions. By using advanced analytical techniques, we provide a scientific foundation for ZJP's potential application in early gastric cancer intervention. Methods Using ultra-high performance liquid chromatography-quadrupole orbitrap high-resolution mass spectrometry (UPLC-Q-Orbitrap HRMS), we identified active components in ZJP. A network pharmacology approach was then applied to construct a "ZJP-compound-target-disease" network. Molecular docking and molecular dynamics simulations were conducted to analyze the stability and interactions of the main active components of ZJP with core protein targets in PLGC. Animal experiments were used to validate significant targets and pathways in vivo. Results Tangeritin, Isorhamnetin, Caffeic Acid, Azelaic Acid, and Adenosine were identified as the main active components of ZJP in the treatment of PLGC, with key targets including PIK3R1, MAPK3, SRC, JAK2, STAT3, and PIK3CA. Molecular docking and molecular dynamics simulations further confirmed the relationship between compounds and target proteins. The potential molecular mechanism of ZJP predicted by network pharmacology analysis was confirmed in PLGC rats. ZJP downregulated IL-6, TNF-α, c-myc, p-MEK1 and p-ERK1/2, effectively reversing the progression of PLGC. Conclusion ZJP can reverse MNNG-induced PLGC, potentially through inhibition of the MEK/ERK/c-myc pathway and regulation of cellular proliferation and apoptosis.
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Affiliation(s)
- Lan Liang
- The First Clinical Medical School, Shaanxi University of Chinese Medicine, Xianyang, People’s Republic of China
- College of Nursing, Shaanxi Energy Institute, Xianyang, People’s Republic of China
| | - Chenming He
- LongHua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China
| | - Xue Han
- Xijing 986 Hospital Department, Air Force Medical University, Xian, People’s Republic of China
| | - Jia Liu
- School of Basic Medical Sciences, Shaanxi University of Chinese Medicine, Xianyang, People’s Republic of China
| | - Liuhong Yang
- School of Basic Medical Sciences, Shaanxi University of Chinese Medicine, Xianyang, People’s Republic of China
| | - Fengjiao Chang
- School of Nursing, Shaanxi University of Chinese Medicine, Xianyang, People’s Republic of China
| | - Yami Zhang
- The Fifth Oncology Department, Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, People’s Republic of China
| | - Jie Lin
- School of Basic Medical Sciences, Shaanxi University of Chinese Medicine, Xianyang, People’s Republic of China
- Shaanxi Provincial Key Laboratory of TCM Constitution and Disease Prevention, Xianyang, People’s Republic of China
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Liu J, Li M, Chen G, Yang J, Jiang Y, Li F, Hua H. Jianwei Xiaoyan granule ameliorates chronic atrophic gastritis by regulating HIF-1α-VEGF pathway. JOURNAL OF ETHNOPHARMACOLOGY 2024; 334:118591. [PMID: 39025161 DOI: 10.1016/j.jep.2024.118591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Revised: 06/19/2024] [Accepted: 07/15/2024] [Indexed: 07/20/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Jianwei Xiaoyan Granule (JWXYG) is the traditional Chinese medicine preparation in Jiangyin Hospital Affiliated to Nanjing University of Chinese Medicine, which has been widely used in clinical treatment of chronic atrophic gastritis (CAG). However, the material basis and potential mechanism of JWXYG in the treatment of CAG are not clear. PURPOSE To explore the material basis and potential mechanism of JWXYG in the treatment of CAG. METHODS In this study, the components of JWXYG were analyzed by HPLC-Q-TOF-MS/MS. Then, the CAG model in rats established by a composite modeling method and MC cell model induced by MNNG were used to explore the improvement effect of JWXYG on CAG. Finally, the potential mechanism of JWXYG in the treatment of CAG was preliminarily predicted based on network pharmacology and validated experimentally. RESULTS Thirty-one components of JWXYG were analyzed through HPLC-Q-TOF-MS/MS, such as albiflorin, paeoniflorin, lobetyolin firstly. Research results in vivo showed that the gastric mucosa became thinner, intestinal metaplasia appeared, the number of glands was reduced, the serum levels of PG I and PG II increased and the contents of G17 and IL-6 reduced in CAG model rats. After 4 weeks of JWXYG (2.70 g/kg) administration, these conditions were significantly improved. In addition, cell viability, migration, and invasion of MNNG-induced MC cells was inhibited by JWXYG treatment (800 μg/mL). Furthermore, the results of network pharmacology indicated that HIF-1 and VEGF signaling pathways might play important roles in the therapeutic process. Then the results of Western blot, immunohistochemistry and immunofluorescence confirmed that with JWXYG treatment, the increased expression of HIF-1α, VEGF and VEGFR2 in gastric issue of CAG rats were restrained. Eventually, potential components of JWXYG in the treatment of CAG were predicted through molecular docking to elucidate the material basis. CONCLUSION JWXYG could inhibit angiogenesis by regulating HIF-1α-VEGF pathway to exert therapeutic effects on CAG. Our study explored the potential mechanisms and material basis of JWXYG in the treatment of CAG and provides experimental data for the clinical rational application of JWXYG.
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Affiliation(s)
- Jia Liu
- Jiangyin Hospital Affiliated to Nanjing University of Chinese Medicine, Jiangyin, 214400, Jiangsu Province, China.
| | - Mengyu Li
- Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Research Center for Traceability and Standardization of TCMs, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, China.
| | - Guobao Chen
- Jiangyin Hospital Affiliated to Nanjing University of Chinese Medicine, Jiangyin, 214400, Jiangsu Province, China.
| | - Junhui Yang
- Jiangyin Hospital Affiliated to Nanjing University of Chinese Medicine, Jiangyin, 214400, Jiangsu Province, China.
| | - Ying Jiang
- Jiangyin Hospital Affiliated to Nanjing University of Chinese Medicine, Jiangyin, 214400, Jiangsu Province, China.
| | - Fang Li
- Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Research Center for Traceability and Standardization of TCMs, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, China.
| | - Haibing Hua
- Jiangyin Hospital Affiliated to Nanjing University of Chinese Medicine, Jiangyin, 214400, Jiangsu Province, China.
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Cheng S, Chen J, Li Q, Nie Y, Ni T, Peng C, Luo X, Yasin P, Zhang S, Tang J, Liu Z. Protective effect of folic acid on MNNG-induced proliferation of esophageal epithelial cells via the PI3K/AKT/mTOR signaling pathway. J Nutr Biochem 2024; 133:109702. [PMID: 39025456 DOI: 10.1016/j.jnutbio.2024.109702] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2023] [Revised: 06/19/2024] [Accepted: 07/12/2024] [Indexed: 07/20/2024]
Abstract
Recent research has revealed that N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) constitutes a significant risk factor in the development of esophageal cancer. Several investigations have elucidated the beneficial impact of folic acid (FA) in safeguarding esophageal epithelial cells against MNNG-induced damage. Therefore, we hypothesized that FA might prevent MNNG-induced proliferation of esophageal epithelial cells by interfering with the PI3K/AKT/mTOR signaling pathway. In vivo experiments, we found that FA antagonized MNNG-induced proliferation of rat esophageal mucosal epithelial echinocytes and activation of the PI3K/AKT/mTOR signaling pathway. In our in vitro experiments, it was observed that acute exposure to MNNG for 24 h led to a decrease in proliferative capacity and inhibition of the PI3K/AKT/mTOR signaling pathway in an immortalized human normal esophageal epithelial cell line (Het-1A), which was also ameliorated by supplementation with FA. We successfully established a Het-1A-T-cell line by inducing malignant transformation in Het-1A cells through exposure to MNNG. Notably, the PI3K/AKT2/mTOR pathway showed early suppression followed by activation during this transition. Next, we observed that FA inhibited cell proliferation and activation of the PI3K/AKT2/mTOR signaling pathway in Het-1A-T malignantly transformed cells. We further investigated the impact of 740Y-P, a PI3K agonist, and LY294002, a PI3K inhibitor, on Het-1A-T-cell proliferation. Overall, our findings show that FA supplementation may be beneficial in safeguarding normal esophageal epithelial cell proliferation and avoiding the development of esophageal cancer by decreasing the activation of the MNNG-induced PI3K/AKT2/mTOR signaling pathway.
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Affiliation(s)
- Suizhi Cheng
- Department of Nutrition and Food Hygiene, School of Public Health, North Sichuan Medical College, Nanchong 637000, China; Department of Pharmacology, School of Pharmacy, North Sichuan Medical College, Nanchong 637000, China
| | - Jin Chen
- Department of Nutrition and Food Hygiene, School of Public Health, North Sichuan Medical College, Nanchong 637000, China
| | - Qianhui Li
- Department of Nutrition and Food Hygiene, School of Public Health, North Sichuan Medical College, Nanchong 637000, China; Department of Pharmacology, School of Pharmacy, North Sichuan Medical College, Nanchong 637000, China
| | - Yuhong Nie
- Department of Nutrition and Food Hygiene, School of Public Health, North Sichuan Medical College, Nanchong 637000, China
| | - Ting Ni
- Department of Nutrition and Food Hygiene, School of Public Health, North Sichuan Medical College, Nanchong 637000, China
| | - Caiting Peng
- Department of Nutrition and Food Hygiene, School of Public Health, North Sichuan Medical College, Nanchong 637000, China
| | - Xi Luo
- Department of Nutrition and Food Hygiene, School of Public Health, North Sichuan Medical College, Nanchong 637000, China
| | - Pazilat Yasin
- Department of Nutrition and Food Hygiene, School of Public Health, North Sichuan Medical College, Nanchong 637000, China
| | - Shumin Zhang
- Department of Biochemistry, School of Basic Medical Sciences, North Sichuan Medical College, Nanchong 637000, China
| | - Jiancai Tang
- Department of Biochemistry, School of Basic Medical Sciences, North Sichuan Medical College, Nanchong 637000, China
| | - Zhenzhong Liu
- Department of Nutrition and Food Hygiene, School of Public Health, North Sichuan Medical College, Nanchong 637000, China.
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Wang YM, Sun JH, Sun RX, Liu XY, Li JF, Li RZ, Du YR, Zhou XZ. Treating chronic atrophic gastritis: identifying sub-population based on real-world TCM electronic medical records. Front Pharmacol 2024; 15:1444733. [PMID: 39170704 PMCID: PMC11335612 DOI: 10.3389/fphar.2024.1444733] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2024] [Accepted: 07/26/2024] [Indexed: 08/23/2024] Open
Abstract
Background and Objective Chronic atrophic gastritis (CAG) is a complex chronic disease caused by multiple factors that frequently occurs disease in the clinic. The worldwide prevalence of CAG is high. Interestingly, clinical CAG patients often present with a variety of symptom phenotypes, which makes it more difficult for clinicians to treat. Therefore, there is an urgent need to improve our understanding of the complexity of the clinical CAG population, obtain more accurate disease subtypes, and explore the relationship between clinical symptoms and medication. Therefore, based on the integrated platform of complex networks and clinical research, we classified the collected patients with CAG according to their different clinical characteristics and conducted correlation analysis on the classification results to identify more accurate disease subtypes to aid in personalized clinical treatment. Method Traditional Chinese medicine (TCM) offers an empirical understanding of the clinical subtypes of complicated disorders since TCM therapy is tailored to the patient's symptom profile. We gathered 6,253 TCM clinical electronic medical records (EMRs) from CAG patients and manually annotated, extracted, and preprocessed the data. A shared symptom-patient similarity network (PSN) was created. CAG patient subgroups were established, and their clinical features were determined through enrichment analysis employing community identification methods. Different clinical features of relevant subgroups were correlated based on effectiveness to identify symptom-botanical botanical drugs correspondence. Moreover, network pharmacology was employed to identify possible biological relationships between screened symptoms and medications and to identify various clinical and molecular aspects of the key subtypes using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Results 5,132 patients were included in the study: 2,699 males (52.60%) and 2,433 females (47.41%). The population was divided into 176 modules. We selected the first 3 modules (M29, M3, and M0) to illustrate the characteristic phenotypes and genotypes of CAG disease subtypes. The M29 subgroup was characterized by gastric fullness disease and internal syndrome of turbidity and poison. The M3 subgroup was characterized by epigastric pain and disharmony between the liver and stomach. The M0 subgroup was characterized by epigastric pain and dampness-heat syndrome. In symptom analysis, The top symptoms for symptom improvement in all three subgroups were stomach pain, bloating, insomnia, poor appetite, and heartburn. However, the three groups were different. The M29 subgroup was more likely to have stomach distention, anorexia, and palpitations. Citrus medica, Solanum nigrum, Jiangcan, Shan ci mushrooms, and Dillon were the most popular botanical drugs. The M3 subgroup has a higher incidence of yellow urine, a bitter tongue, and stomachaches. Smilax glabra, Cyperus rotundus, Angelica sinensis, Conioselinum anthriscoides, and Paeonia lactiflora were the botanical drugs used. Vomiting, nausea, stomach pain, and appetite loss are common in the M0 subgroup. The primary medications are Scutellaria baicalensis, Smilax glabra, Picrorhiza kurroa, Lilium lancifolium, and Artemisia scoparia. Through GO and KEGG pathway analysis, We found that in the M29 subgroup, Citrus medica, Solanum nigrum, Jiangcan, Shan ci mushrooms, and Dillon may exert their therapeutic effects on the symptoms of gastric distension, anorexia, and palpitations by modulating apoptosis and NF-κB signaling pathways. In the M3 subgroup, Smilax glabra, Cyperus rotundus, Angelica sinensis, Conioselinum anthriscoides, and Paeonia lactiflora may be treated by NF-κB and JAK-STAT signaling pathway for the treatment of stomach pain, bitter mouth, and yellow urine. In the M0 subgroup, Scutellaria baicalensis, Smilax glabra, Picrorhiza kurroa, Lilium lancifolium, and Artemisia scoparia may exert their therapeutic effects on poor appetite, stomach pain, vomiting, and nausea through the PI3K-Akt signaling pathway. Conclusion Based on PSN identification and community detection analysis, CAG population division can provide useful recommendations for clinical CAG treatment. This method is useful for CAG illness classification and genotyping investigations and can be used for other complicated chronic diseases.
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Affiliation(s)
- Yu-man Wang
- Graduate School of Hebei University of Traditional Chinese Medicine, Hebei, China
| | - Jian-hui Sun
- Hebei Hospital of Traditional Chinese Medicine, Hebei, China
- Hebei Key Laboratory of Turbidity and Toxicology, Hebei, China
| | - Run-xue Sun
- Hebei Hospital of Traditional Chinese Medicine, Hebei, China
- Hebei Key Laboratory of Turbidity and Toxicology, Hebei, China
| | - Xiao-yu Liu
- Graduate School of Hebei University of Traditional Chinese Medicine, Hebei, China
| | - Jing-fan Li
- Graduate School of Hebei University of Traditional Chinese Medicine, Hebei, China
| | - Run-ze Li
- Graduate School of Hebei University of Traditional Chinese Medicine, Hebei, China
| | - Yan-ru Du
- Hebei Hospital of Traditional Chinese Medicine, Hebei, China
- Hebei Key Laboratory of Turbidity and Toxicology, Hebei, China
- Hebei Provincial Key Laboratory of Integrated Traditional and Western Medicine Research on Gastroenterology, Hebei, China
| | - Xue-zhong Zhou
- School of Computer and Information Technology, Beijing Jiaotong University, Beijing, China
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Zhang M, Zhong J, Song Z, Xu Q, Chen Y, Zhang Z. Regulatory mechanisms and potential therapeutic targets in precancerous lesions of gastric cancer: A comprehensive review. Biomed Pharmacother 2024; 177:117068. [PMID: 39018877 DOI: 10.1016/j.biopha.2024.117068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Revised: 06/27/2024] [Accepted: 06/27/2024] [Indexed: 07/19/2024] Open
Abstract
Precancerous lesions of gastric cancer (PLGC) represent a critical pathological stage in the transformation from normal gastric mucosa to gastric cancer (GC). The global incidence of PLGC has been rising over the past few decades, with a trend towards younger onset ages. Increasing evidence suggests that early prevention and treatment of PLGC can effectively reverse the malignant development of gastric mucosal epithelial cells. However, there is currently a lack of effective therapeutic drugs and methods. Recent years have witnessed substantial advancements in PLGC research, with the elucidation of novel regulatory mechanisms offering promising avenues for clinical intervention and drug development. This review aims to delineate potential targets for early prevention and diagnosis of GC while exploring innovative approaches to PLGC management. This article focuses on elucidating the regulatory mechanisms of the inflammatory microenvironment, bile acids (BA), glycolysis, autophagy, apoptosis, ferroptosis, and cellular senescence. We pay particular attention to potential therapeutic targets for PLGC, with the goal of providing insights and theoretical basis for clinical research on PLGC.
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Affiliation(s)
- Maofu Zhang
- Clinical College of Traditional Chinese Medicine, Gansu University of Chinese Medicine, Lanzhou, Gansu 730000, China
| | - Jialin Zhong
- Clinical College of Traditional Chinese Medicine, Gansu University of Chinese Medicine, Lanzhou, Gansu 730000, China
| | - Zhongyang Song
- Department of Oncology, Affiliated Hospital of Gansu University of Traditional Chinese Medicine, Lanzhou, Gansu 730020, China
| | - Qian Xu
- Clinical College of Traditional Chinese Medicine, Gansu University of Chinese Medicine, Lanzhou, Gansu 730000, China
| | - Yuchan Chen
- Clinical College of Traditional Chinese Medicine, Gansu University of Chinese Medicine, Lanzhou, Gansu 730000, China
| | - Zhiming Zhang
- Department of Oncology, Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou, Gansu 730050, China.
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Xu X, Liu Y, Gong Q, Ma L, Wei W, Zhao L, Luo Z. PARP1 promotes EGFR-TKI drug-resistance via PI3K/AKT pathway in non-small-cell lung cancer. Cancer Chemother Pharmacol 2024; 94:209-221. [PMID: 38609654 DOI: 10.1007/s00280-024-04668-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2024] [Accepted: 04/02/2024] [Indexed: 04/14/2024]
Abstract
PURPOSE Tyrosine kinase inhibitor (TKI) resistance is the main type of drug resistance in lung cancer patients with epidermal growth factor receptor (EGFR) mutations, but its underlying mechanism remains unclear. The purpose of this work was to investigate the mechanism by which PARP1 regulates EGFR-TKI resistance to identify potential targets for combating drug resistance. METHODS The GEO databases, TCGA databases, western blot and qPCR studies were used to investigate the expression of PARP1 in lung cancer cells and tissues and its correlation with the prognosis of lung cancer. The expression of PARP1 in lung cancer TKI resistant cell PC9-ER and TKI sensitive cell PC9 was analyzed by qPCR and western blot. After knocking down of PARP1, CCK-8 assays, colony formation, flow cytometry were used to investigate its impact on erlotinib sensitivity, cell survival, cell cycle, and apoptosis. RNA-seq was used to investigate the mechanism by which PARP1 participates in EGFR-TKI resistance, and the results were validated in vitro and in vivo studies. RESULTS PARP1 was highly expressed in both lung cancer tissues and cells. Subsequently, increased PARP1 expression was observed in PC9-ER compared with its parental cell line. Knockdown of PARP1 increased erlotinib sensitivity, promoted cell apoptosis, and suppressed cell growth. RNA-seq and previous studies have shown that the PI3K/AKT/mTOR/P70S6K pathway is involved in PARP1-mediated TKI resistance, and these results were confirmed by Western blot in vitro and in vivo. CONCLUSION PARP1 may serve as a potential therapeutic target for reversing EGFR-TKI resistance in NSCLC via the PI3K/AKT/mTOR/P70S6K pathway.
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Affiliation(s)
- Xianping Xu
- Department of Oncology, The Affiliated Hospital of Southwest Medical University, No. 25 Taiping Street, Jiangyang District Luzhou, Sichuan, 646000, China
- Department of Oncology, Chongqing Genaral Hospital, No.118, Xingguang Avenue, Liangjiang New Area, Chongqing, 401147, China
| | - Yu Liu
- Department of Oncology, Chongqing Genaral Hospital, No.118, Xingguang Avenue, Liangjiang New Area, Chongqing, 401147, China
| | - Qiang Gong
- Department of Hematology, Southwest Hospital, Third Military Medical University (Army Medical University), Gaotanyan Road Street, Shapingba District, Chongqing, 400038, China
| | - Le Ma
- Department of Hematology, Southwest Hospital, Third Military Medical University (Army Medical University), Gaotanyan Road Street, Shapingba District, Chongqing, 400038, China
| | - Wei Wei
- Department of Oncology, Chongqing Genaral Hospital, No.118, Xingguang Avenue, Liangjiang New Area, Chongqing, 401147, China
| | - Linqiong Zhao
- Department of Oncology, Chongqing Genaral Hospital, No.118, Xingguang Avenue, Liangjiang New Area, Chongqing, 401147, China
| | - Zhibin Luo
- Department of Oncology, The Affiliated Hospital of Southwest Medical University, No. 25 Taiping Street, Jiangyang District Luzhou, Sichuan, 646000, China.
- Department of Oncology, Chongqing Genaral Hospital, No.118, Xingguang Avenue, Liangjiang New Area, Chongqing, 401147, China.
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Wang R, Zhao Y, Zhou L, Lin F, Wan M, Gan A, Wu B, Yan T, Jia Y. Costunolide ameliorates MNNG-induced chronic atrophic gastritis through inhibiting oxidative stress and DNA damage via activation of Nrf2. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 130:155581. [PMID: 38810553 DOI: 10.1016/j.phymed.2024.155581] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Revised: 01/27/2024] [Accepted: 04/01/2024] [Indexed: 05/31/2024]
Abstract
BACKGROUND Chronic atrophic gastritis (CAG) is a chronic digestive disease. Modern research has revealed substantial evidence indicating that the progression of CAG is closely linked to the occurrence of oxidative stress-induced DNA damage and apoptosis in the gastric mucosa. Additionally, research has indicated that Costunolide (COS), the primary active compound found in Aucklandiae Radix, a traditional herb, exhibits antioxidant properties. Nevertheless, the therapeutic potential of COS in treating CAG and its molecular targets have not yet been determined. PURPOSE The objective of this research was to explore the potential gastric mucosal protective effects and mechanisms of COS against N-Methyl-N´-nitro-N-nitrosoguanidine (MNNG)-induced CAG. METHODS Firstly, the MNNG-induced rat CAG model was established in vivo. Occurrence of CAG was detected through macroscopic examination of the stomachs and H&E staining. Additionally, we assessed oxidative stress, DNA damage, and apoptosis using biochemical detection, Western blot, immunohistochemistry and immunofluorescence. Then, an in vitro model was developed to induce MNNG-induced damage in GES-1 cells, and the occurrence of cell damage was determined by Hoechst 33,342 staining and flow cytometry. Finally, the key targets of COS for the treatment of CAG were identified through molecular docking, cellular thermal shift assay (CETSA), and inhibitor ML385. RESULTS In vivo studies demonstrated that COS promotes the expression of Nrf2 in gastric tissues. This led to an increased expression of SOD, GSH, HO-1, while reducing the production of MDA. Furthermore, COS inhibited DNA damage and apoptosis by suppressing the expression of γH2AX and PARP1 in gastric tissues. In vitro studies showed that COS effectively reversed apoptosis induced by MNNG in GES-1 cells. Additionally, COS interacted with Nrf2 to promote its expression. Furthermore, the expression levels of SOD, GSH, and HO-1 were augmented, while the generation of ROS and MDA was diminished. CONCLUSIONS Our results indicate that COS exhibits therapeutic effects on CAG through the promotion of Nrf2 expression and inhibition of oxidative stress and DNA damage. Therefore, COS has the potential to provide new drugs for the treatment of CAG.
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Affiliation(s)
- Ruixuan Wang
- School of Functional Food and Wine, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning Province, 110016, China
| | - Youdong Zhao
- School of Functional Food and Wine, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning Province, 110016, China
| | - Lei Zhou
- School of Functional Food and Wine, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning Province, 110016, China
| | - Fei Lin
- School of Functional Food and Wine, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning Province, 110016, China
| | - Meiqi Wan
- School of Functional Food and Wine, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning Province, 110016, China
| | - Anna Gan
- School of Functional Food and Wine, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning Province, 110016, China
| | - Bo Wu
- School of Functional Food and Wine, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning Province, 110016, China
| | - Tingxu Yan
- School of Functional Food and Wine, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning Province, 110016, China.
| | - Ying Jia
- School of Functional Food and Wine, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning Province, 110016, China.
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21
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Jia J, Zhao H, Li F, Zheng Q, Wang G, Li D, Liu Y. Research on drug treatment and the novel signaling pathway of chronic atrophic gastritis. Biomed Pharmacother 2024; 176:116912. [PMID: 38850667 DOI: 10.1016/j.biopha.2024.116912] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Revised: 06/04/2024] [Accepted: 06/06/2024] [Indexed: 06/10/2024] Open
Abstract
BACKGROUND Chronic atrophic gastritis (CAG) is a global digestive system disease and one of the important causes of gastric cancer. The incidence of CAG has been increasing yearly worldwide. PURPOSE This article reviews the latest research on the common causes and future therapeutic targets of CAG as well as the pharmacological effects of corresponding clinical drugs. We provide a detailed theoretical basis for further research on possible methods for the treatment of CAG and reversal of the CAG process. RESULTS CAG often develops from chronic gastritis, and its main pathological manifestation is atrophy of the gastric mucosa, which can develop into gastric cancer. The drug treatment of CAG can be divided into agents that regulate gastric acid secretion, eradicate Helicobacter. pylori (H. pylori), protect gastric mucous membrane, or inhibit inflammatory factors according to their mechanism of action. Although there are limited specific drugs for the treatment of CAG, progress is being made in defining the pathogenesis and therapeutic targets of the disease. Growing evidence shows that NF-κB, PI3K/AKT, Wnt/ β-catenin, MAPK, Toll-like receptors (TLRs), Hedgehog, and VEGF signaling pathways play an important role in the development of CAG.
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Affiliation(s)
- Jinhao Jia
- Featured Laboratory for Biosynthesis and Target Discovery of Active Components of Traditional Chinese Medicine, School of Traditional Chinese Medicine & Binzhou Hospital of Traditional Chinese Medicine, Binzhou Medical University, Yantai, Shandong 264003, PR China
| | - Huijie Zhao
- Featured Laboratory for Biosynthesis and Target Discovery of Active Components of Traditional Chinese Medicine, School of Traditional Chinese Medicine & Binzhou Hospital of Traditional Chinese Medicine, Binzhou Medical University, Yantai, Shandong 264003, PR China
| | - Fangfei Li
- Shum Yiu Foon Shum Bik Chuen Memorial Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, Special Administrative Region of China
| | - Qiusheng Zheng
- Featured Laboratory for Biosynthesis and Target Discovery of Active Components of Traditional Chinese Medicine, School of Traditional Chinese Medicine & Binzhou Hospital of Traditional Chinese Medicine, Binzhou Medical University, Yantai, Shandong 264003, PR China; Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, School of Pharmacy, Shihezi University, Shihezi, Xinjiang 832003, PR China
| | - Guoli Wang
- Featured Laboratory for Biosynthesis and Target Discovery of Active Components of Traditional Chinese Medicine, School of Traditional Chinese Medicine & Binzhou Hospital of Traditional Chinese Medicine, Binzhou Medical University, Yantai, Shandong 264003, PR China
| | - Defang Li
- Featured Laboratory for Biosynthesis and Target Discovery of Active Components of Traditional Chinese Medicine, School of Traditional Chinese Medicine & Binzhou Hospital of Traditional Chinese Medicine, Binzhou Medical University, Yantai, Shandong 264003, PR China; Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, School of Pharmacy, Shihezi University, Shihezi, Xinjiang 832003, PR China.
| | - Ying Liu
- Featured Laboratory for Biosynthesis and Target Discovery of Active Components of Traditional Chinese Medicine, School of Traditional Chinese Medicine & Binzhou Hospital of Traditional Chinese Medicine, Binzhou Medical University, Yantai, Shandong 264003, PR China.
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Li SY, Xu DQ, Chen YY, Fu RJ, Tang YP. Several major herb pairs containing Coptidis rhizoma: a review of key traditional uses, constituents and compatibility effects. Front Pharmacol 2024; 15:1399460. [PMID: 38983920 PMCID: PMC11231094 DOI: 10.3389/fphar.2024.1399460] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Accepted: 06/04/2024] [Indexed: 07/11/2024] Open
Abstract
Herb compatibility is the soul of traditional Chinese Medicine prescriptions. Coptidis rhizoma (CR) (Coptis chinensis Franch., Coptis deltoidea C.Y.Cheng et Hsiao, or Coptis teeta Wall.; family Ranunculaceae), is a well-known herb. The bitter and cold nature of CR can irritate the spleen and stomach, and certain ingredients in CR may trigger allergic reactions. Herb combinations can help alleviate the side effects caused by CR. Through data analysis and literature research, there are many herbs combined with CR have a high frequency, but only a few are currently used as formulae in clinical practice. The results showed that these six herb pairs are usually widely studied or used as prescriptions in the clinic. This paper describes the six herb pairs from the key traditional uses, changes in bioactive constituents, and compatibility effects, especially with Euodiae fructus (family Rutaceae), Scutellariae radix (family Lamiaceae), Magnoliae Officinalis cortex (family Magnoliaceae), Glycyrrhizae radix et rhizoma (family Fabaceae), Ginseng radix et rhizoma (family Araliaceae), and Aucklandiae radix (family Asteraceae), and found that herbs are more effective when used in combination. Therefore, it is feasible to establish some methods to study herb pairs comprehensively from different perspectives. This paper aims to provide the latest and most comprehensive information on the six herb pairs and summarize the pattern of CR compatibility effects. It aims to attract more attention, and further experimental studies will be conducted to investigate and evaluate the effects of herb pairs containing CR. These data can also provide valuable references for researchers and also provide more possibilities for future applications in clinical practice and new drug development.
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Affiliation(s)
- Shi-Yu Li
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi University of Chinese Medicine, Xi'an, Shaanxi Province, China
| | - Ding-Qiao Xu
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi University of Chinese Medicine, Xi'an, Shaanxi Province, China
| | - Yan-Yan Chen
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi University of Chinese Medicine, Xi'an, Shaanxi Province, China
- Wuxi Institute of Integrated Chinese and Western Medicine, and Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu Province, China
| | - Rui-Jia Fu
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi University of Chinese Medicine, Xi'an, Shaanxi Province, China
| | - Yu-Ping Tang
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi University of Chinese Medicine, Xi'an, Shaanxi Province, China
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Zhou Z, Hu C, Cui B, You L, An R, Liang K, Wang X. Ginsenoside Rg1 Suppresses Pyroptosis via the NF-κB/NLRP3/GSDMD Pathway to Alleviate Chronic Atrophic Gastritis In Vitro and In Vivo. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2024. [PMID: 38855973 DOI: 10.1021/acs.jafc.4c01271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2024]
Abstract
Chronic atrophic gastritis (CAG) is characterized by the loss of gastric glandular cells, which are replaced by the intestinal-type epithelium and fibrous tissue. Ginsenoside Rg1 (Rg1) is the prevalent ginsenoside in ginseng, with a variety of biological activities, and is usually added to functional foods. As a novel form of programmed cell death (PCD), pyroptosis has received substantial attention in recent years. Despite the numerous beneficial effects, the curative impact of Rg1 on CAG and whether its putative mechanism is partially via inhibiting pyroptosis still remain unknown. To address this gap, we conducted a study to explore the mechanisms underlying the potential anti-CAG effect of Rg1. We constructed a CAG rat model using a multifactor comprehensive method. A cellular model was developed by using 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) combined with Nigericin as a stimulus applied to GES-1 cells. After Rg1 intervention, the levels of inflammatory indicators in the gastric tissue/cell supernatant were reduced. Rg1 relieved oxidative stress via reducing the myeloperoxidase (MPO) and malonaldehyde (MDA) levels in the gastric tissue and increasing the level of superoxide dismutase (SOD). Additionally, Rg1 improved MNNG+Nigericin-induced pyroptosis in the morphology and plasma membrane of the cells. Further research supported novel evidence for Rg1 in the regulation of the NF-κB/NLRP3/GSDMD pathway and the resulting pyroptosis underlying its therapeutic effect. Moreover, by overexpression and knockout of GSDMD in GES-1 cells, our findings suggested that GSDMD might serve as the key target in the effect of Rg1 on suppressing pyroptosis. All of these offer a potential theoretical foundation for applying Rg1 in ameliorating CAG.
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Affiliation(s)
- Zehua Zhou
- Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Cheng Hu
- Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Bo Cui
- Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Lisha You
- Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Rui An
- Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Kun Liang
- Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Xinhong Wang
- Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
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Chen L, He T, Wang R, Liu H, Wang X, Li H, Jing M, Zhou X, Wei S, Zou W, Zhao Y. Integrated Approaches Revealed the Therapeutic Mechanisms of Zuojin Pill Against Gastric Mucosa Injury in a Rat Model with Chronic Atrophic Gastritis. Drug Des Devel Ther 2024; 18:1651-1672. [PMID: 38774485 PMCID: PMC11108080 DOI: 10.2147/dddt.s454758] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Accepted: 05/03/2024] [Indexed: 05/24/2024] Open
Abstract
BACKGROUND The Zuojin Pill (ZJP) is widely used for treating chronic atrophic gastritis (CAG) in clinical practice, effectively ameliorating symptoms such as vomiting, pain, and abdominal distension in patients. However, the underlying mechanisms of ZJP in treating CAG has not been fully elucidated. PURPOSE This study aimed to clarify the characteristic function of ZJP in the treatment of CAG and its potential mechanism. METHODS The CAG model was established by alternant administrations of ammonia solution and sodium deoxycholate, as well as an irregular diet. Therapeutic effects of ZJP on body weight, serum biochemical indexes and general condition were analyzed. HE staining and AB-PAS staining were analyzed to characterize the mucosal injury and the thickness of gastric mucosa. Furthermore, network pharmacology and molecular docking were used to predict the regulatory mechanism and main active components of ZJP in CAG treatment. RT-PCR, immunohistochemistry, immunofluorescence and Western blotting were used to measure the expression levels of apoptosis-related proteins, gastric mucosal barrier-associated proteins and PI3K/Akt signaling pathway proteins. RESULTS The results demonstrated that ZJP significantly improved the general state of CAG rats, alleviated weight loss and gastric histological damage and reduced the serum biochemical indicators. Network pharmacology and molecular docking found that ZJP in treating CAG by inhibiting inflammation, suppressing apoptosis, and protecting the gastric mucosal barrier via the PI3K/Akt signaling pathway. Further experiments confirmed that ZJP obviously modulated the expression of key proteins involved in gastric mucosal cell apoptosis, such as Bax, Bad, Apaf-1, cleaved-caspase-3, cleaved-caspase-9, Cytochrome C, Bcl-2, and Bcl-xl. Moreover, ZJP significantly reversed the protein expression of Occludin, ZO-1, Claudin-4 and E-cadherin. CONCLUSION Our study revealed that ZJP treats CAG by inhibiting the PI3K/Akt signaling pathway. This research provided a scientific basis for the rational use of ZJP in clinical practice.
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Affiliation(s)
- Lisheng Chen
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China
- Department of Pharmacy Department, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China
| | - Tingting He
- Division of Integrative Medicine, The Fifth Medical Center of General Hospital of PLA, Beijing, People’s Republic of China
| | - Ruilin Wang
- Division of Integrative Medicine, The Fifth Medical Center of General Hospital of PLA, Beijing, People’s Republic of China
| | - Honghong Liu
- Integrated TCM & Western Medicine Department, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China
| | - Xin Wang
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China
- Department of Pharmacy Department, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China
| | - Haotian Li
- Department of Pharmacy Department, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China
| | - Manyi Jing
- Department of Pharmacy Department, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China
| | - Xuelin Zhou
- Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing, People’s Republic of China
| | - Shizhang Wei
- Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University, Beijing, People’s Republic of China
| | - Wenjun Zou
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China
| | - Yanling Zhao
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China
- Department of Pharmacy Department, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China
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Gong H, Zhao N, Zhu C, Luo L, Liu S. Treatment of gastric ulcer, traditional Chinese medicine may be a better choice. JOURNAL OF ETHNOPHARMACOLOGY 2024; 324:117793. [PMID: 38278376 DOI: 10.1016/j.jep.2024.117793] [Citation(s) in RCA: 14] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Revised: 12/30/2023] [Accepted: 01/18/2024] [Indexed: 01/28/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Gastric ulcer (GU) is the injury of the gastric mucosa caused by the stimulation of various pathogenic factors penetrating the deep mucosal muscle layer. An increasing number of studies have shown that traditional Chinese medicine (TCM) is highly effective in treating GU due to its multitarget, multilevel, and multi-pathway effects. AIM OF THE STUDY To review the latest research progress in the treatment of GU by TCM, including clinical and experimental studies, focusing on the target and mechanism of action of drugs and providing a theoretical basis for the treatment of GU by natural herbs. MATERIALS AND METHODS Electronic databases (PubMed, Elsevier, Springer, Web of Science, and CNKI) were searched using the keywords "gastric ulcer", "gastric mucosal lesion", "TCM" and or paired with "peptic ulcer" and "natural drugs" for studies published in the last fifteen years until 2023. RESULTS TCM, including single components of natural products, Chinese patent medicines (CPM), and TCM decoction, is expected to treat GU by regulating various mechanisms, such as redox balance, inflammatory factors, angiogenesis, gastric mucosal protective factors, intestinal flora, apoptosis, and autophagy. CONCLUSIONS We discussed and summarized the mechanism of TCM in the treatment of GU, which provided a sufficient basis for TCM treatment of GU.
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Affiliation(s)
- Haiying Gong
- School of Traditional Chinese Medicine, Capital Medical University, Beijing, China; Department of Gastroenterology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Ning Zhao
- Wuxi School of Medicine, Jiangnan University, Wuxi, China
| | - Conglei Zhu
- Department of Pharmacy, Fuyang People's Hospital, Fuyang, Anhui, China
| | - Lin Luo
- School of Basic Medical Sciences, Beijing Key Laboratory of Neural Regeneration and Repair, Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
| | - Sen Liu
- School of Basic Medical Sciences, Beijing Key Laboratory of Neural Regeneration and Repair, Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China.
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Yan-Rui W, Xue-Er Y, Mao-Yu D, Ya-Ting L, Bo-Heng L, Miao-Jie Z, Li Z. Research on the signaling pathway and the related mechanism of traditional Chinese medicine intervention in chronic gastritis of the "inflammation-cancer transformation". Front Pharmacol 2024; 15:1338471. [PMID: 38698812 PMCID: PMC11063381 DOI: 10.3389/fphar.2024.1338471] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Accepted: 04/05/2024] [Indexed: 05/05/2024] Open
Abstract
Objective: The aim of this study is to uncover the traditional Chinese medicine (TCM) treatments for chronic gastritis and their potential targets and pathways involved in the "inflammation-cancer" conversion in four stages. These findings can provide further support for future research into TCM and its active components. Materials and methods: The literature search encompassed PubMed, Web of Science, Google Scholar, CNKI, WanFang, and VIP, employing keywords such as "chronic gastritis", "gastric cancer", "traditional Chinese medicine", "medicinal herb", "Chinese herb", and "natural plant". Results: Herbal remedies may regulate the signaling pathways linked to the advancement of chronic gastritis. Under the multi-target and multi-pathway independent or combined reaction, the inflammatory microenvironment may be enhanced, leading to repair of damaged gastric mucosal cells, buffering the progress of mucosal atrophic degeneration via the decrease of inflammatory factor expression, inhibition of oxidative stress-induced damage, facilitation of microvascular neovascularization in the gastric mucosa and regulation of the processes of gastric mucosal cell differentiation and proliferation. Simultaneously, the decreased expression of inflammatory factors may impact the expression of associated oncogenes and regulate the malignant proliferation of cells, thereby achieving the treatment and prevention objectives of gastric cancer through the reduction of cell metastasis and apoptosis. Conclusion: Chinese medicine formulations and individual drugs can be utilised at various stages of the "inflammation-cancer" progression of chronic gastritis to prevent and treat gastric cancer in a multi-level, multi-targeted, and multi-directional fashion. This can provide guidance for the accurate application of medicines during different stages of "inflammation-cancer" transformation. New insights into the mechanism of inflammation-cancer transformation and the development of novel drugs for chronic gastritis can be gained through an extensive investigation of TCM treatment in this condition.
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Affiliation(s)
- Wang Yan-Rui
- Dongzhimen Hospital of Beijing University of Chinese Medicine, Beijing, China
- Beijing University of Chinese Medicine, Beijing, China
| | - Yan Xue-Er
- Dongzhimen Hospital of Beijing University of Chinese Medicine, Beijing, China
- Beijing University of Chinese Medicine, Beijing, China
| | - Ding Mao-Yu
- Beijing University of Chinese Medicine, Beijing, China
- Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China
| | - Lu Ya-Ting
- Dongzhimen Hospital of Beijing University of Chinese Medicine, Beijing, China
- Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China
| | - Lu Bo-Heng
- Beijing University of Chinese Medicine, Beijing, China
| | - Zhai Miao-Jie
- Dongzhimen Hospital of Beijing University of Chinese Medicine, Beijing, China
- Beijing University of Chinese Medicine, Beijing, China
| | - Zhu Li
- Dongzhimen Hospital of Beijing University of Chinese Medicine, Beijing, China
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Guo Y, Jia X, Du P, Wang J, Du Y, Li B, Xue Y, Jiang J, Cai Y, Yang Q. Mechanistic insights into the ameliorative effects of Xianglianhuazhuo formula on chronic atrophic gastritis through ferroptosis mediated by YY1/miR-320a/TFRC signal pathway. JOURNAL OF ETHNOPHARMACOLOGY 2024; 323:117608. [PMID: 38158098 DOI: 10.1016/j.jep.2023.117608] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Revised: 12/11/2023] [Accepted: 12/14/2023] [Indexed: 01/03/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Xianglianhuazhuo formula (XLHZ) has a potential therapeutic effect on chronic atrophic gastritis (CAG). However, the specific molecular mechanism remains unclear. AIM OF THE STUDY To evaluate the effect of XLHZ on CAG in vitro and in vivo and its potential mechanisms. METHODS A rat model of CAG was established using a composite modeling method, and the pathological changes and ultrastructure of gastric mucosa were observed. YY1/miR-320a/TFRC and ferroptosis-related molecules were detected. An MNNG-induced gastric epithelial cell model was established in vitro to evaluate the inhibitory effect of XLHZ on cell ferroptosis by observing cell proliferation, migration, invasion, apoptosis, and molecules related to ferroptosis. The specific mechanism of action of XLHZ in treating CAG was elucidated by silencing or overexpression of targets. RESULTS In vivo experiments showed that XLHZ could improve the pathological status and ultrastructure of gastric mucosa and inhibit ferroptosis by regulating the YY1/miR-320a/TFRC signaling pathway. The results in vitro demonstrated that transfection of miR-320a mimics inhibited cell proliferation, migration, and invasion while promoting cell apoptosis. MiR-320a targeted TFRC and inhibited ferroptosis. Overexpression of TFRC reversed the inhibitory effect of miR-320a overexpression on cell proliferation. The effect of XLHZ was consistent with that of miR-320a. YY1 targeted miR-320a, and its overexpression promoted ferroptosis. CONCLUSION XLHZ inhibited ferroptosis by regulating the YY1/miR-320a/TFRC signaling pathway, ultimately impeding the progression of CAG.
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Affiliation(s)
- Yuxi Guo
- Department of Spleen and Stomach Diseases, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Heibei, 050011, China
| | - Xuemei Jia
- Department of Spleen and Stomach Diseases, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Heibei, 050011, China
| | - Pengli Du
- Department of Spleen and Stomach Diseases, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Heibei, 050011, China; Hebei Key Laboratory of Integrated Chinese and Western Medicine for Gastroenterology Research, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050011, China; Hebei Key Laboratory of Turbidity Toxin Syndrome, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050011, China
| | - Jie Wang
- Department of Spleen and Stomach Diseases, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Heibei, 050011, China
| | - Yao Du
- Department of Spleen and Stomach Diseases, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Heibei, 050011, China; Hebei Key Laboratory of Integrated Chinese and Western Medicine for Gastroenterology Research, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050011, China; Hebei Key Laboratory of Turbidity Toxin Syndrome, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050011, China
| | - Bolin Li
- Department of Spleen and Stomach Diseases, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Heibei, 050011, China; Hebei Key Laboratory of Integrated Chinese and Western Medicine for Gastroenterology Research, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050011, China; Hebei Key Laboratory of Turbidity Toxin Syndrome, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050011, China
| | - Yucong Xue
- College of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, Heibei, 050200, China
| | - Jianming Jiang
- College of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, Heibei, 050200, China
| | - Yanru Cai
- Department of Spleen and Stomach Diseases, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Heibei, 050011, China; Hebei Key Laboratory of Integrated Chinese and Western Medicine for Gastroenterology Research, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050011, China; Hebei Key Laboratory of Turbidity Toxin Syndrome, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050011, China.
| | - Qian Yang
- Department of Spleen and Stomach Diseases, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Heibei, 050011, China; Hebei Key Laboratory of Integrated Chinese and Western Medicine for Gastroenterology Research, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050011, China; Hebei Key Laboratory of Turbidity Toxin Syndrome, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050011, China.
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Li M, Chen XL, Yu ZP, Li YL, Hong LH, Cai YX, Kong LY, Luo JG. New indolequinazoline alkaloids from the fruits of Tetradium ruticarpum. Fitoterapia 2024; 174:105843. [PMID: 38301937 DOI: 10.1016/j.fitote.2024.105843] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2023] [Revised: 01/01/2024] [Accepted: 01/29/2024] [Indexed: 02/03/2024]
Abstract
In this research, five new indolequinazoline alkaloids (1-5), along with six known indolequinazoline alkaloids (6-11) were obtained from the fruits of Tetradium ruticarpum. Their structures were elucidated through comprehensive spectroscopic data of 1D and 2D NMR, HRESIMS and ECD spectra. Additionally, all isolates were assayed for their SIRT1 inhibitory activities in vitro and compounds 2, 7, 10 and 11 exhibited activities with IC50 values ranged from 43.16 to 118.35 μM.
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Affiliation(s)
- Mu Li
- Jiangsu Key Laboratory of Bioactive Natural Product Research, State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, PR China
| | - Xin-Lin Chen
- Jiangsu Key Laboratory of Bioactive Natural Product Research, State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, PR China
| | - Zhan-Peng Yu
- Jiangsu Key Laboratory of Bioactive Natural Product Research, State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, PR China
| | - Ya-Lin Li
- Jiangsu Key Laboratory of Bioactive Natural Product Research, State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, PR China
| | - Li-Hong Hong
- Jiangsu Key Laboratory of Bioactive Natural Product Research, State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, PR China
| | - Yu-Xing Cai
- Jiangsu Key Laboratory of Bioactive Natural Product Research, State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, PR China
| | - Ling-Yi Kong
- Jiangsu Key Laboratory of Bioactive Natural Product Research, State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, PR China..
| | - Jian-Guang Luo
- Jiangsu Key Laboratory of Bioactive Natural Product Research, State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, PR China..
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Xiong M, Chen X, Wang H, Tang X, Wang Q, Li X, Ma H, Ye X. Combining transcriptomics and network pharmacology to reveal the mechanism of Zuojin capsule improving spasmolytic polypeptide-expressing metaplasia. JOURNAL OF ETHNOPHARMACOLOGY 2024; 318:117075. [PMID: 37625606 DOI: 10.1016/j.jep.2023.117075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Revised: 08/12/2023] [Accepted: 08/21/2023] [Indexed: 08/27/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Spasmolytic polypeptide-expressing metaplasia (SPEM) is a gastric precancerous lesion (GPL). Zuojin capsule (ZJC), consisting of Coptis chinensis Franch. (Ranunculaceae, recorded in the Chinese Pharmacopoeia as Rhizoma Coptidis) and Tetradium ruticarpum (A.Juss.) T.G.Hartley (Rutaceae, recorded in the Chinese Pharmacopoeia as Fructus Evodiae), has long been used for various gastrointestinal diseases. However, the effect and mechanism of ZJC on SPEM remain unclear. AIM OF THE STUDY To clarify the role of ZJC in improving SPEM and study its mechanism. MATERIALS AND METHODS The study utilized SPEM mice induced by 250 mg/kg body weight of tamoxifen (TAM) to assess the effects of ZJC and investigate its possible mechanisms. A strategy of transcriptomics combined with network pharmacology was conducted to explore the targets and mechanisms of ZJC in improving SPEM. The "ingredients-target-pathway" network was constructed, and the possible connections were verified by RT-qPCR and Western blot assays. RESULTS ZJC significantly attenuated the abnormal serological indices, destruction of the gastric mucosal structure, hyperplasia of gastric pits, increased gastric mucus, massive secretion of CD44 and TFF2, oxyntic atrophy and massive proliferation of stem/progenitor cells in TAM-induced SPEM mice. Combined transcriptomics and network pharmacology analysis, 50 core targets of ZJC related to SPEM improvement were obtained. KEGG results showed that the core targets were significantly enriched in the cell cycle, and PI3K-AKT signaling pathway. The top-ranked targets according to PPI network analysis were CDK1, CCNB1, and CCNA2, which are also associated with cell cycle. Combined experiments demonstrated that ZJC can induce G2/M phase cycle arrest and inhibit TAM-induced malignant proliferation by regulating abnormal activation of cell cycle-related proteins such as CDK1, CCNB1, CCNA2 and PI3K-AKT signaling pathways. CONCLUSIONS ZJC may improve TAM-induced SPEM by inhibiting abnormal activation of cell cycle-related proteins (CDK1, CCNB1, CCNA2) and PI3K-AKT signaling pathway. This finding supports the use of ZJC, a famous traditional Chinese medicine compound, as a potential treatment for gastric precancerous lesions.
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Affiliation(s)
- Mengyuan Xiong
- Engineering Research Center of Coptis Development and Utilization (Ministry of Education), School of Life Sciences, Southwest University, Chongqing, 400715, China.
| | - Xiantao Chen
- Engineering Research Center of Coptis Development and Utilization (Ministry of Education), School of Life Sciences, Southwest University, Chongqing, 400715, China.
| | - Hongmei Wang
- Engineering Research Center of Coptis Development and Utilization (Ministry of Education), School of Life Sciences, Southwest University, Chongqing, 400715, China.
| | - Xiang Tang
- Engineering Research Center of Coptis Development and Utilization (Ministry of Education), School of Life Sciences, Southwest University, Chongqing, 400715, China.
| | - Qiaojiao Wang
- Engineering Research Center of Coptis Development and Utilization (Ministry of Education), School of Life Sciences, Southwest University, Chongqing, 400715, China.
| | - Xuegang Li
- College of Pharmaceutical Sciences, Southwest University, Chongqing, 400715, China.
| | - Hang Ma
- College of Pharmaceutical Sciences, Southwest University, Chongqing, 400715, China.
| | - Xiaoli Ye
- Engineering Research Center of Coptis Development and Utilization (Ministry of Education), School of Life Sciences, Southwest University, Chongqing, 400715, China.
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Sun Z, Liu Y, Deng H, Wang S, Zhang J, Xing C, Xu C. Modified Chaishao Liujunzi Decoction inhibits bile acid-induced gastric intestinal metaplasia: from network prediction to experimental verification. Aging (Albany NY) 2023; 15:13998-14018. [PMID: 38096029 PMCID: PMC10756100 DOI: 10.18632/aging.205285] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Accepted: 11/02/2023] [Indexed: 12/21/2023]
Abstract
Modified Chaishao Liujunzi Decoction (MCLD) is a traditional Chinese medicine formula that is used mainly to improve clinical symptoms, alleviate gastric mucosal inflammation, and improve gastric mucosal lesions in patients with gastric intestinal metaplasia (GIM). GIM is considered a precancerous gastric cancer (GC) lesion (PLGC) and exploring effective intervention measures for GIM is of great importance for the prevention of GC. The purpose of this study was to reveal the potential molecular mechanism of MCLD in improving GIM induced by bile acid (BA) using network pharmacology and experimental validation. Through network pharmacology, we speculated that MCLD could act on GIM by driving the epidermal growth factor receptor (EGFR)/PI3K/AKT/mammalian target of rapamycin (mTOR) pathway. After that, we used deoxycholic acid (DCA) to treat GES-1 cells to simulate BA-induced GIM and observed the effects of MCLD treatment. The results indicate that MCLD can significantly inhibit DCA-induced cell proliferation and down-regulate the expression of pro-inflammatory cytokines and intestinal-specific markers. At the same time, MCLD also negatively regulated the expression of genes and proteins of the EGFR/PI3K/AKT/mTOR pathway. Combination with EGFR agonists and inhibitors suggested that MCLD may improve GIM by inhibiting the EGFR/PI3K/AKT/mTOR pathway, which may be related to its inhibition of DCA-induced cell proliferation through this pathway. In conclusion, MCLD may improve BA-induced GIM through the EGFR/PI3K/AKT/mTOR pathway, as predicted by network pharmacology, and is a potential Chinese medicine prescription for the treatment or reversal of GIM.
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Affiliation(s)
- Zheyu Sun
- Changchun University of Chinese Medicine, Changchun 130021, Jilin Province, P.R. China
| | - Yuna Liu
- Beijing Hospital of Integrated Traditional Chinese and Western Medicine, Beijing 100038, P.R. China
| | - Haiyan Deng
- Beijing Hospital of Integrated Traditional Chinese and Western Medicine, Beijing 100038, P.R. China
| | - Shaohua Wang
- Beijing Hospital of Integrated Traditional Chinese and Western Medicine, Beijing 100038, P.R. China
| | - Jing Zhang
- Beijing Hospital of Integrated Traditional Chinese and Western Medicine, Beijing 100038, P.R. China
| | - Chongyi Xing
- Changchun University of Chinese Medicine, Changchun 130021, Jilin Province, P.R. China
| | - Chunfeng Xu
- Beijing Hospital of Integrated Traditional Chinese and Western Medicine, Beijing 100038, P.R. China
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Song J, Xu X, He S, Zhang H, Wang N, Bai Y, Li B, Zhang S. Identification of the therapeutic effect and molecular mechanism of Coptis chinensis Franch. and Magnolia officinalis var. biloba on chronic gastritis. JOURNAL OF ETHNOPHARMACOLOGY 2023; 317:116864. [PMID: 37393026 DOI: 10.1016/j.jep.2023.116864] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Revised: 06/12/2023] [Accepted: 06/27/2023] [Indexed: 07/03/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Traditional Chinese medicine (TCM) theory believes that clearing heat and promoting dampness is the main treatment method for chronic gastritis. Coptis chinensis Franch. has the effects of clearing heat, detoxifying, and anti-inflammatory; Magnolia officinalis var. biloba can be used to treat abdominal pain, cough, and asthma. Coptis chinensis Franch. and Magnolia officinalis var. biloba can regulate the balance of intestinal microbiota and inhibit inflammatory reactions. AIM This study will verify the therapeutic effect of Coptis chinensis Franch. and Magnolia officinalis var. biloba on chronic gastritis, and explore its mechanism through transcriptome sequencing. METHODS Firstly, a rat chronic gastritis model was established, and the anal temperature and body weight changes of the rats before and after modeling were observed. Next, H&E staining, TUNEL assay and ELISA assay were performed on rat gastric mucosal tissues. Subsequently, the key fractions of Coptis chinensis Franch. and Magnolia officinalis var. biloba were obtained by high performance liquid chromatography (HPLC), and a GES-1 cell inflammation model was constructed to select the optimal monomer. Finally, the mechanism of action of Coptis chinensis Franch. and Magnolia officinalis var. biloba was explored through RNA seq. RESULTS Compared with the control group, the rats in the administered group were in better condition, with higher anal temperature, reduced inflammatory response in gastric mucosal tissue and reduced apoptosis. The optimal fraction Coptisine was subsequently determined by HPLC and GES-1 cell model. RNA-seq analysis revealed that DEG was significantly enriched in ribosomes, NF-κB signaling pathway, etc. The key genes TPT1 and RPL37 were subsequently obtained. CONCLUSIONS This study verified the therapeutic effects of Coptis chinensis Franch. and Magnolia officinalis var. biloba on chronic gastritis by in vivo and in vitro experiments in rats, identified Coptisine as the optimal component, and obtained two potential target genes.
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Affiliation(s)
- Jin Song
- Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, China; Beijing Institute of Chinese Medicine, Beijing, 100010, China
| | - Xiaolong Xu
- Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, China; Beijing Institute of Chinese Medicine, Beijing, 100010, China
| | - Shasha He
- Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, China; Beijing Institute of Chinese Medicine, Beijing, 100010, China
| | - Huicun Zhang
- Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, China; Beijing Institute of Chinese Medicine, Beijing, 100010, China
| | - Ning Wang
- Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, China; Beijing Institute of Chinese Medicine, Beijing, 100010, China
| | - Yunjing Bai
- Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, China; Beijing Institute of Chinese Medicine, Beijing, 100010, China
| | - Bo Li
- Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, China; Beijing Institute of Chinese Medicine, Beijing, 100010, China.
| | - Shengsheng Zhang
- Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, China.
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He Y, Chen L, Li X, Wang X, Liu H, Chang L, Jing M, Li H, Wei S, Zhao Y. Clinical Evidence and Potential Mechanisms of Traditional Chinese Medicine for the Treatment of Chronic Gastritis: An Updated Systematic Review and Meta-analysis. J Herb Med 2023; 42:100761. [DOI: 10.1016/j.hermed.2023.100761] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2025]
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Zhang Z, Zhu T, Zhang L, Xing Y, Yan Z, Li Q. Critical influence of cytokines and immune cells in autoimmune gastritis. Autoimmunity 2023; 56:2174531. [PMID: 36762543 DOI: 10.1080/08916934.2023.2174531] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/11/2023]
Abstract
Gastric cancer (GC) is a type of the most common cancers. Autoimmune gastritis (AIG) and infection with Helicobacter pylori (HP) are the risk factors of triggering GC. With the emphasis on the treatment of HP, the incidence and prevalence of HP infection in population is decreasing. However, AIG lacks accurate diagnosis and treatment methods, which occupies high cancer risk factors. AIG is controlled by the immune environment of the stomach, including immune cells, inflammatory cells, and infiltrating intercellular material. Various immune cells or cytokines play a central role in the process of regulating gastric parietal cells. Abnormal expression levels of cytokines involved in immunity are bound to face the risk of tumorigenesis. Therefore, it is particularly important for preventing or treating AIG and avoiding the risk of gastric cancer to clarify the confirmed action mode of immune cells and cytokines in the gastric system. Herein, we briefly reviewed the role of the immune environment under AIG, focussing on describing these double-edged effects between immune cells and cytokines, and pointing out potential research challenges.
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Affiliation(s)
- Zepeng Zhang
- Kunshan Hospital of Chinese Medicine, Suzhou, Jiangsu, China
| | - Tongtong Zhu
- Kunshan Hospital of Traditional Chinese and Western Medicine, Suzhou, Jiangsu, China
| | - Lei Zhang
- Kunshan Hospital of Chinese Medicine, Suzhou, Jiangsu, China
| | - Yanchao Xing
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Zhiqiang Yan
- Kunshan Hospital of Chinese Medicine, Suzhou, Jiangsu, China
| | - Qingsong Li
- Kunshan Hospital of Chinese Medicine, Suzhou, Jiangsu, China
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Yang L, Liu X, Zhu J, Zhang X, Li Y, Chen J, Liu H. Progress in traditional Chinese medicine against chronic gastritis: From chronic non-atrophic gastritis to gastric precancerous lesions. Heliyon 2023; 9:e16764. [PMID: 37313135 PMCID: PMC10258419 DOI: 10.1016/j.heliyon.2023.e16764] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Revised: 05/13/2023] [Accepted: 05/26/2023] [Indexed: 06/15/2023] Open
Abstract
Chronic gastritis (CG) is a persistent inflammation of the gastric mucosa that can cause uncomfortable symptoms in patients. Traditional Chinese medicine (TCM) has been widely used to treat CG due to its precise efficacy, minimal side effects, and holistic approach. Clinical studies have confirmed the effectiveness of TCM in treating CG, although the mechanisms underlying this treatment have not yet been fully elucidated. In this review, we summarized the clinical research and mechanisms of TCM used to treat CG. Studies have shown that TCM mechanisms for CG treatment include H. pylori eradication, anti-inflammatory effects, immune modulation, regulation of gastric mucosal cell proliferation, apoptosis, and autophagy levels.
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Affiliation(s)
- Liangjun Yang
- Tongde Hospital of Zhejiang Province, Hangzhou 310012, China
| | - Xinying Liu
- Tongde Hospital of Zhejiang Province, Hangzhou 310012, China
| | - Jiajie Zhu
- Tongde Hospital of Zhejiang Province, Hangzhou 310012, China
| | - Xi Zhang
- Guangzhou University of Chinese Medicine, Guangzhou 510405, China
| | - Ya Li
- Lin ‘an Hospital of Traditional Chinese Medicine, Hangzhou 311300, China
| | - Jiabing Chen
- Tongde Hospital of Zhejiang Province, Hangzhou 310012, China
| | - Haiyan Liu
- Tongde Hospital of Zhejiang Province, Hangzhou 310012, China
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Dhondrup R, Tidwell T, Zhang X, Feng X, Lobsang D, Hua Q, Geri D, Suonan DC, Fan G, Samdrup G. Tibetan medicine Liuwei Muxiang pills (LWMX pills) effectively protects mice from chronic non-atrophic gastritis. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2023; 115:154826. [PMID: 37167846 DOI: 10.1016/j.phymed.2023.154826] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Revised: 04/05/2023] [Accepted: 04/16/2023] [Indexed: 05/13/2023]
Abstract
BACKGROUND Chronic non-atrophic gastritis (CNG) is the most common type of chronic gastritis. If not actively treated, it may induce gastric cancer (GC). Western medicine is effective in CNG, but there are more adverse reactions after long-term medication, and it is easy to relapse after treatment, which affects patients' health and life. Tibetan medicine Liuwei Muxiang Pills (LWMX pills) is a traditional Tibetan medicine compound, which has a unique curative effect in the treatment of gastric inflammation, especially chronic non-atrophic gastritis. However, the mechanisms of LWMX pills for treatment CNG still remain poor known. PURPOSE The aim of this study was to evaluate the therapeutic intervention potential of Tibetan medicine LWMX pills on CNG and explore its potential mechanisms in mice models. METHODS The mice models was established to evaluate the therapeutic effect of LWMX pills on CNG. The main components of LWMX pills were analyzed by GC-MS. HE staining, immunohistochemistry, proteomics and Western Blot were used to analyze the potential mechanism of LWMX pills for CNG treatment. RESULTS In the present study, LWMX pills containing costunolide, dehydrocostuslactone and antioxidants were found. IF results showed that the expression of ALDH1B1 in the control group was significantly lower than that in the model group in the gastric mucosa tissue, and the expression of ALDH1B1 was significantly lower in the 25 mg/ml LWMX Pills group (one month) and 25 mg/ml LWMX Pills group (two months) than in the model group. IHC revealed that model group samples expressed higher levels of Furin than 25 mg/ml LWMX Pills group samples, as evidenced by very strong staining of Furin in gastric mucosal cells. However, AMY2 staining in gastric mucosal cells did not differ significantly between the treated and control groups. the protein expression levels of these proteins were decreased in 25 mg/mL LWMX pills. Meanwhile, we found that the CAM1 protein expression in the in 25 mg/ml LWMX pills group (two mouths) was increased compared to the in 25 mg/ml LWMX pills group (one mouths).Western blotting showed that the protein expression levels of Furin, AMY2A, CPA3, ALDH1B1, Cam1, COXII, IL-6, IL-1β were decreased in 25 mg/mL LWMX pills. Meanwhile, that the CAM1 protein expression in the in 25 mg/ml LWMX pills group (two mouths) was increased compared to the in 25 mg/ml LWMX pills group (one mouths). CONCLUSION 25mg/ml LWMX pill treatment for one month had better therapeutic effect on mice CNG. Further proteomic results showed that LWMX pills maintain gastric function by inhibiting inflammation and oxidative stress, and we also found that LWMX pills regulate the expression of proteins associated with cancer development (Amy2, Furin).
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Affiliation(s)
- Rinchen Dhondrup
- Tibetan Medical College of Qinghai University, Xining 810016, Qinghai, People's Republic of China.
| | - Tawni Tidwell
- University of Wisconsin-Madison, Center for Healthy Minds, Madison, WI, 53703 United States
| | - XiaoKang Zhang
- Jingjie PTM Bio (Hangzhou) Co., Ltd., Hangzhou 310018, Zhejiang, People's Republic of China
| | - Xuemei Feng
- Qinghai Provincial Tibetan Hospital, Xining 810007, Qinghai, People's Republic of China
| | - Dhondrup Lobsang
- Tibetan Medical College of Qinghai University, Xining 810016, Qinghai, People's Republic of China
| | - Qincuo Hua
- Qinghai Provincial Tibetan Hospital, Xining 810007, Qinghai, People's Republic of China
| | - Duojie Geri
- Tibetan Medical College of Qinghai University, Xining 810016, Qinghai, People's Republic of China
| | - Duojie Caidan Suonan
- Tibetan Medical College of Qinghai University, Xining 810016, Qinghai, People's Republic of China
| | - Gang Fan
- School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, Sichuan, People's Republic of China
| | - Gyal Samdrup
- Tibetan Medical College of Qinghai University, Xining 810016, Qinghai, People's Republic of China
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Study on quality control of Zuojin pill by HPLC fingerprint with quantitative analysis of multi-components by single marker method and antioxidant activity analysis. J Pharm Biomed Anal 2023; 225:115075. [PMID: 36603393 DOI: 10.1016/j.jpba.2022.115075] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Revised: 09/22/2022] [Accepted: 09/23/2022] [Indexed: 11/06/2022]
Abstract
Current quality control methods for Zuojin Pill (ZJP) lack comprehensiveness and practicability. This study aimed to develop a comprehensive strategy for the quality evaluation of ZJP and the prediction of potential bioactive components in ZJP. First, an HPLC method with excellent separation of main components was developed and was used to establish the chromatographic fingerprint of ZJP. Similarities were calculated by comparing 28 batches of ZJPs with the reference fingerprint and the resulting similarity values were all greater than 0.976. The 28 samples were classified into different groups according to their origins by Hierarchical Cluster Analysis, Principal component analysis, and orthogonal partial least squares discriminant analysis. Based on the classification, eight quality markers (Q-Markers) affecting the quality of ZJP were discovered. Then, using berberine as an internal standard substance, quantitative analysis of multi-components by single marker method (QAMS) for the determination of eight Q-markers was developed. The results showed that there was no significant difference between QAMS and external standard method (P>0.05). Finally, using an off-line antioxidant system and partial least-squares model (PLS), the fingerprint-efficacy relationship of ZJP was constructed to explore and predict the bioactive components in ZJP. The present study strategy could be also applied to comprehensive quality study of other TCMs.
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Liao W, Wen Y, Wang J, Zhao M, Lv S, Chen N, Li Y, Wan L, Zheng Q, Mou Y, Zhao Z, Tang J, Zeng J. Gallic acid alleviates gastric precancerous lesions through inhibition of epithelial mesenchymal transition via Wnt/β-catenin signaling pathway. JOURNAL OF ETHNOPHARMACOLOGY 2023; 302:115885. [PMID: 36328204 DOI: 10.1016/j.jep.2022.115885] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Revised: 10/25/2022] [Accepted: 10/26/2022] [Indexed: 06/16/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Gallic acid (GA) is a natural polyphenolic compound derived from Rhus chinensis Mill. with a variety of biological activities such as astringent sweat, cough, dysentery, hemostasis, and detoxification, and is widely used in China as a treatment for cough, bleeding, and gastrointestinal disorders. In recent years, the anticancer activity of GA has been demonstrated in a variety of cancers, affecting multiple cellular pathways associated with cancer onset, development and progression. AIM OF THE STUDY To investigate the role and potential mechanism of GA on gastric precancerous lesions (GPL), the key turning point of gastritis to gastric cancer, with the aim of delaying, blocking or reversing the dynamic overall process of "inflammation-cancer transformation" and thus blocking GPL to prevent the development of gastric cancer. MATERIALS AND METHODS In this study, we established N-Nitroso-N-methylurea (MNU)-induced GPL mice model and induced precancerous lesions of gastric cancer cells (MC), i.e. epithelial mesenchymal transition (EMT), in human gastric mucosal epithelial cells (GES-1) with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). We used conventional pathology, immunohistochemistry, RNA sequencing, Western blot and other techniques to study the therapeutic effect of GA on GPL and its possiblemechanism in vitro and in vivo. RESULTS The results showed that compared with normal GES-1 cells, MC cells had the characteristics of malignant cells such as abnormal proliferation, invasion and metastasis, accompanied by decreased expression of EMT-related protein E-cadherin and increased expression of N-cadherin and Vimentin. GA can inhibit the malignant behavior of MC cell proliferation and induce its G0/G1 phase arrest, which is achieved by downregulating the Wnt/β-catenin signaling pathway and thereby inhibiting the EMT process. However, when we incubated with the Wnt pathway activator (Wnt agonist 1), the effect of GA was reversed. Furthermore, analysis of human gastric specimens showed that activation of the Wnt/β-catenin pathway was significantly associated with GPL pathological changes. Meanwhile, GA reversed MNU-induced intestinal metaplasia and partial dysplasia in GPL mice. CONCLUSION Taken together, these results indicate that GA prevents the occurrence and development of GPL by inhibiting the Wnt/β-catenin signaling pathway and then inhibiting the EMT process, which may become potential candidates for the treatment of GPL.
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Affiliation(s)
- Wenhao Liao
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
| | - Yueqiang Wen
- School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
| | - Jing Wang
- Department of Obstetrics and Gynecology, Bishan District Hospital of Traditional Chinese Medicine, Chongqing, China.
| | - Maoyuan Zhao
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
| | - Shangbin Lv
- School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
| | - Nianzhi Chen
- State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, China.
| | - Yuchen Li
- College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
| | - Lina Wan
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
| | - Qiao Zheng
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
| | - Yu Mou
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
| | - Ziyi Zhao
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, Sichuan, China.
| | - Jianyuan Tang
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, Sichuan, China.
| | - Jinhao Zeng
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, Sichuan, China; Department of Geriatrics, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, Sichuan, China.
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Zhang J, Yin Y, Xu Q, Che X, Yu C, Ren Y, Li D, Zhao J. Integrated serum pharmacochemistry and investigation of the anti-gastric ulcer effect of Zuojin pill in rats induced by ethanol. PHARMACEUTICAL BIOLOGY 2022; 60:1417-1435. [PMID: 35938492 PMCID: PMC9361771 DOI: 10.1080/13880209.2022.2098345] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Revised: 05/02/2022] [Accepted: 06/30/2022] [Indexed: 06/15/2023]
Abstract
CONTEXT Zuojin Pill (ZJP) has been used to treat gastrointestinal problems in China for hundreds of years. OBJECTIVE To discover more potential active ingredients and evaluate the gastroprotective mechanisms of ZJP. MATERIALS AND METHODS An approach involving UPLC-Q-Orbitrap HRMS and serum pharmacochemistry was established to screen the multiple chemical constituents of ZJP. Male Sprague-Dawley (SD) rats were divided into six groups: normal control, ulcer control, omeprazole (30 mg/kg), and three ZJP groups (1.0, 2.0 and 4.0 g/kg). After oral treatment with ZJP or omeprazole for 7 days, all groups except the normal control group were orally administered 5 mL/kg ethanol to induce gastric ulceration. Histopathological assessment of gastric tissue was performed by haematoxylin and eosin staining. Antioxidant parameters and inflammatory mediators were determined using ELISA Kit and immunohistochemical analysis. RESULTS Ninety components were identified in ZJP. Among them, 23 prototypes were found in rat serum after oral administration of ZJP. The ulcer inhibition was over 90.0% for all the ZJP groups. Compared with the ulcer control rats, ZJP (4.0 g/kg) enhanced the antioxidant capacity of gastric tissue: superoxide dismutase (1.33-fold), catalase (2.61-fold), glutathione (2.14-fold), and reduced the malondialdehyde level (0.48-fold). Simultaneously, the ZJP meaningfully lowered the content of tumour necrosis factor-α (0.76-fold), interleukin-6 (0.66-fold), myeloperoxidase (0.21-fold), and nuclear factor kappa B (p65) (0.62-fold). DISCUSSION AND CONCLUSIONS This study showed ZJP could mitigate ethanol-induced rat gastric ulcers, which might benefit from the synergistic actions of multiple ingredients. The findings could support the quality control and clinical trials of ZJP.
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Affiliation(s)
- Jiaying Zhang
- School of Pharmacy, Binzhou Medical University, Yantai, China
| | - Yi Yin
- School of Pharmacy, Binzhou Medical University, Yantai, China
| | - Qianqian Xu
- School of Pharmacy, Binzhou Medical University, Yantai, China
| | - Xiaoqing Che
- School of Pharmacy, Binzhou Medical University, Yantai, China
| | - Chen Yu
- School of Pharmacy, Binzhou Medical University, Yantai, China
| | - Yan Ren
- School of Pharmacy, Binzhou Medical University, Yantai, China
| | - Dongsheng Li
- College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, China
| | - Juanjuan Zhao
- School of Pharmacy, Binzhou Medical University, Yantai, China
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Chu YM, Wang TX, Jia XF, Yang Y, Shi ZM, Cui GH, Huang QY, Ye H, Zhang XZ. Fuzheng Nizeng Decoction regulated ferroptosis and endoplasmic reticulum stress in the treatment of gastric precancerous lesions: A mechanistic study based on metabolomics coupled with transcriptomics. Front Pharmacol 2022; 13:1066244. [PMID: 36506541 PMCID: PMC9727497 DOI: 10.3389/fphar.2022.1066244] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Accepted: 11/07/2022] [Indexed: 11/24/2022] Open
Abstract
Background: Fuzheng Nizeng Decoction (FZNZ) has a history of decades in gastric precancerous lesions (GPL) treatment, which has shown clear clinical efficacy. Blocking GPL is a key measure to reduce the incidence of gastric cancer (GC). Therefore, we aim to investigate the mechanism of FZNZ-induced ferroptosis and endoplasmic reticulum (ER) in MNNG-induced gastric precancerous lesion (MC) cells, which has been rarely studied in Traditional Chinese Medicine (TCM). Methods: First, CCK8 and lactate dehydrogenase assays were conducted to study the potential effect of FZNZ on MC cells. Second, combined transcriptomic and metabolomic analysis were used to explore the effect and mechanism of FZNZ. Functionally, the occurrence of ferroptosis was assessed by transmission electron microscopy morphological observation and measurement of ferrous iron levels, lipid peroxidation, and glutathione levels. Finally, the expression levels of mRNAs or proteins related to ferroptosis and ER stress were determined by qPCR or western blot assays, respectively. Results: FZNZ inhibited MC cells viability and induced cell death. By metabolomics coupled with transcriptomics analysis, we found that the mechanism of FZNZ treatment induced ferroptosis and was related to glutathione metabolism and ER stress. We then, for the first time, found that FZNZ induced ferroptosis, which contributed to an increase in intracellular ferrous iron, reactive oxygen species, and malondialdehyde and a decrease in glutathione. Meanwhile, the protein level of glutathione peroxidase 4 (GPX4) was decreased. The mRNA levels of ATF3/CHOP/CHAC1, which are related to ferroptosis and ER stress, were also upregulated. Conclusion: Our results elaborate that FZNZ could induce ferroptosis and ER stress in MC cells, and reduce GPX4/GSH. ATF3/CHOP/CHAC1 may play a crosstalk role, which provides a new molecular mechanism for the treatment of GPL.
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Affiliation(s)
- Ying-Ming Chu
- Department of Integrated Traditional Chinese and Western Medicine, Peking University First Hospital, Institute of Integrated Traditional Chinese and Western Medicine, Peking University, Beijing, China
| | - Ting-Xin Wang
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, China
| | - Xiao-Fen Jia
- Department of Integrated Traditional Chinese and Western Medicine, Peking University First Hospital, Institute of Integrated Traditional Chinese and Western Medicine, Peking University, Beijing, China
| | - Yao Yang
- Department of Integrated Traditional Chinese and Western Medicine, Peking University First Hospital, Institute of Integrated Traditional Chinese and Western Medicine, Peking University, Beijing, China
| | - Zong-Ming Shi
- Department of Integrated Traditional Chinese and Western Medicine, Peking University First Hospital, Institute of Integrated Traditional Chinese and Western Medicine, Peking University, Beijing, China
| | - Guang-Hui Cui
- Department of Integrated Traditional Chinese and Western Medicine, Peking University First Hospital, Institute of Integrated Traditional Chinese and Western Medicine, Peking University, Beijing, China
| | - Qiu-Yue Huang
- Department of Integrated Traditional Chinese and Western Medicine, Peking University First Hospital, Institute of Integrated Traditional Chinese and Western Medicine, Peking University, Beijing, China
| | - Hui Ye
- Department of Integrated Traditional Chinese and Western Medicine, Peking University First Hospital, Institute of Integrated Traditional Chinese and Western Medicine, Peking University, Beijing, China,*Correspondence: Hui Ye, ; Xue-Zhi Zhang,
| | - Xue-Zhi Zhang
- Department of Integrated Traditional Chinese and Western Medicine, Peking University First Hospital, Institute of Integrated Traditional Chinese and Western Medicine, Peking University, Beijing, China,*Correspondence: Hui Ye, ; Xue-Zhi Zhang,
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Zhang X, Gao R, Zhou Z, Sun J, Tang X, Li J, Zhou X, Shen T. Uncovering the mechanism of Huanglian-Wuzhuyu herb pair in treating nonalcoholic steatohepatitis based on network pharmacology and experimental validation. JOURNAL OF ETHNOPHARMACOLOGY 2022; 296:115405. [PMID: 35644437 DOI: 10.1016/j.jep.2022.115405] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 05/21/2022] [Accepted: 05/23/2022] [Indexed: 05/05/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE The Huanglian-Wuzhuyu herb pair (HWHP) is a classic Chinese herbal formula consisting of the root of Coptis chinensis Franch and dried, nearly mature scented fruit of Tetradium ruticarpum (A.Juss.) T.G.Hartley. It is widely utilized to treat gastrointestinal and liver diseases such as diarrhea, dysentery, cholestasis, hepatocellular carcinoma, and nonalcoholic steatohepatitis (NASH). However, the mechanism of HWHP in treating NASH remains poorly understood. AIM OF THE STUDY This study investigated the mechanisms of HWHP in NASH treatment via network pharmacology and validated the results through in vivo experiment using mouse models. MATERIALS AND METHODS The compounds and targets corresponding to the active ingredients of HWHP were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database. The genes associated with NASH were obtained from the DisGeNET database. Cytoscape software was employed to construct a "drug-ingredient-target-disease" network. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were employed to analyze the related signaling pathways affected by HWHP. Moreover, AutoDock software was used to assess the potential binding affinity between the key targets of the hub pathway and the bioactive compounds. Subsequently, in vivo experiment was conducted to verify the findings of network pharmacology. RESULTS A total of 41 active compounds and 198 targets of HWHP were screened, of which 51 common targets were related to NASH. GO functional enrichment analysis revealed that HWHP may affect NASH by modulating inflammatory response. KEGG pathway enrichment suggested that the NOD-like receptor (NLR) signaling pathway may play an important role in treating NASH. Molecular docking results demonstrated that most HWHP components were successfully docked to NLRP3 with good binding energy. In vivo experiments revealed that HWHP alleviated liver inflammation, improved liver steatosis, reduced TC, TG, LDL-C, ALT, and AST, decreased mRNA expressions of IL-6, IL-18, and TNF-α in the liver, and lowered the expressions of NLRP3, pro-IL-1β, and ASC protein. Also, immunohistochemical findings presented downregulation of caspase-1 and IL-1β by HWHP. CONCLUSIONS The results disclosed that HWHP ameliorates NASH in mice by reducing inflammation and liver steatosis via inhibition of NLRP3 inflammasome. This study revealed the mechanism of HWHP in treating NASH through experiments.
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Affiliation(s)
- Xiaobo Zhang
- School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
| | - Rui Gao
- School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
| | - Zhen Zhou
- Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, TAS7000, Australia.
| | - Jiayi Sun
- Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
| | - Xuehua Tang
- Academic Department, Chengdu Hemoyunyin Medical Laboratory Co, Ltd, 611135, China.
| | - Jialiang Li
- School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
| | - Xin Zhou
- School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
| | - Tao Shen
- School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
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Zheng S, Xue T, Wang B, Guo H, Liu Q. Application of network pharmacology in the study of mechanism of Chinese medicine in the treatment of ulcerative colitis: A review. FRONTIERS IN BIOINFORMATICS 2022; 2:928116. [PMID: 36304327 PMCID: PMC9580908 DOI: 10.3389/fbinf.2022.928116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Accepted: 08/23/2022] [Indexed: 11/17/2022] Open
Abstract
Network pharmacology is a research method based on a multidisciplinary holistic analysis of biological systems, which coincides with the idea of the holistic view of traditional Chinese medicine. In this review, we summarized the use of network pharmacology technology through studying Chinese medicine single medicine or Chinese medicine compound research ideas and methods for the treatment of ulcerative colitis, based on the application of the current network pharmacology in Chinese medicine research, including the important role in the mechanism of the prediction and verification, to search for new ideas for disease diagnosis and treatment, this study summarizes the application of network pharmacology in the treatment of ulcerative colitis in traditional Chinese medicine, including monotherapy and compound therapy, and considers that relevant research studies have fully demonstrated the function characteristics of the multi-component, multi-target, and multi-pathway of traditional Chinese medicine, and can also explain the connotation of “selecting appropriate treatment methods according to the differences and similarities of pathogenesis” of traditional Chinese medicine. Finally, we raised important questions about the prospects and limitations of network pharmacology, such as differences caused by different data collection methods, a considerable lag, and so on.
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Affiliation(s)
- Shihao Zheng
- Graduate School, Hebei University of Traditional Chinese Medicine, Shijiazhuang, China
| | - Tianyu Xue
- Graduate School, Hebei University of Traditional Chinese Medicine, Shijiazhuang, China
| | - Bin Wang
- Graduate School, Hebei University of Traditional Chinese Medicine, Shijiazhuang, China
| | - Haolin Guo
- Graduate School, Hebei University of Traditional Chinese Medicine, Shijiazhuang, China
| | - Qiquan Liu
- Graduate School, Hebei University of Traditional Chinese Medicine, Shijiazhuang, China
- Department of Spleen and Stomach, First Affiliated Hospital of Hebei University of Traditional Chinese Medicine, Shijiazhuang, China
- *Correspondence: Qiquan Liu,
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Ma X, Xie S, Wang R, Wang Z, Jing M, Li H, Wei S, Liu H, Li J, He Q, Zhao Y. Metabolomics Profiles Associated with the Treatment of Zuojin Pill on Patients with Chronic Nonatrophic Gastritis. Front Pharmacol 2022; 13:898680. [PMID: 35899115 PMCID: PMC9310101 DOI: 10.3389/fphar.2022.898680] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Accepted: 06/03/2022] [Indexed: 11/13/2022] Open
Abstract
Objective: Chronic nonatrophic gastritis (CNG) is the most common digestive disease. In China, Zuojin pill (ZJP) is considered an effective medicine formula for CNG. However, its efficacy and mechanism have never been explored. In order to understand how and why ZJP demonstrates therapeutic effect on CNG, a clinical trial was conducted. Metabolomics was used to explore its deep mechanism. Methods: A total of 14 patients with CNG were recruited from October 2020 to March 2021 (ChiCTR2000040549). The endoscopy and histopathological changes were evaluated as efficacy. Serum samples were prepared and detected by performing widely targeted metabolome using UPLC. Multivariate statistical analysis was conducted to identify potential differential metabolites and signaling pathways. Last, the signal-related inflammatory factors containing COX-2, IL-4, and IL-17 were confirmed via immunohistochemical staining and enzyme-linked immunosorbent assay. Results: ZJP was able to alleviate several indexes of mucosal injury under endoscopy and histology. Erosion and bile reflux, but not red plaques and hemorrhage, were downregulated by ZJP. In addition, it could remarkably alleviate active chronic inflammation. A total of 14 potential metabolites, namely, hypoxanthine, adipic acid, D-ribono-1,4-lactone, L-sepiapterin, imidazoleacetic acid, sebacate, ADP-ribose, 4-hydroxybenzyl alcohol, 11,12-EET, 15-OxoETE, 12-OxoETE, (±)8-HETE, glycyrrhizinate, and DL-aminopimelic acid, were discriminated by metabolomics. Moreover, certain amino acid metabolism got significance during the disease progress and treatment. The related inflammatory factors including COX-2, IL-4, and IL-17 were inhibited by ZJP in both mucosa and serum. Conclusion: All these results indicated that ZJP partially acts as an inflammatory suppressor to regulate comprehensive metabolism disorders. This might be an important mechanism of ZJP in the treatment of CNG.
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Affiliation(s)
- Xiao Ma
- Department of Pharmacy, Chinese PLA General Hospital, Beijing, China
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Shuying Xie
- Department of Pharmacy, Chinese PLA General Hospital, Beijing, China
| | - Ruilin Wang
- Division of Integrative Medicine, The Fifth Medical Center, General Hospital of PLA, Beijing, China
| | - Zhongxia Wang
- Division of Integrative Medicine, The Fifth Medical Center, General Hospital of PLA, Beijing, China
| | - Manyi Jing
- Department of Pharmacy, Chinese PLA General Hospital, Beijing, China
| | - Haotian Li
- Department of Pharmacy, Chinese PLA General Hospital, Beijing, China
| | - Shizhang Wei
- Department of Pharmacy, Chinese PLA General Hospital, Beijing, China
- Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing, China
| | - Honghong Liu
- Division of Integrative Medicine, The Fifth Medical Center, General Hospital of PLA, Beijing, China
| | - Jianyu Li
- Division of Integrative Medicine, The Fifth Medical Center, General Hospital of PLA, Beijing, China
| | - Qingyong He
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yanling Zhao
- Department of Pharmacy, Chinese PLA General Hospital, Beijing, China
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Cheng S, Che L, Yang Q, Sun R, Nie Y, Shi H, Ding Y, Wang L, Du Z, Liu Z. Folic acid ameliorates N-methyl-N′-nitro-N-nitrosoguanidine-induced esophageal inflammation via modulation of the NF-κB pathway. Toxicol Appl Pharmacol 2022; 447:116087. [DOI: 10.1016/j.taap.2022.116087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Revised: 05/20/2022] [Accepted: 05/21/2022] [Indexed: 12/24/2022]
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Yu H, Liu C, Wang J, Han J, Zhang F, Zhou X, Wen Y, Shen T. miRNA and miRNA target genes in intervention effect of Zhuyu pill on cholestatic rat model. JOURNAL OF ETHNOPHARMACOLOGY 2022; 283:114709. [PMID: 34626777 DOI: 10.1016/j.jep.2021.114709] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Revised: 09/23/2021] [Accepted: 10/04/2021] [Indexed: 06/13/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Zhuyu pill (ZYP), an effective prescription of traditional Chinese medicine, is composed of Coptis chinensis Franch. and Tetradium ruticarpum (A. Jussieu) T. G. Hartley and has shown potential anticholestatic effects. However, its mechanism of action in treating cholestasis remains unclear. Since post-transcriptional control of mRNA by micro-RNAs (miRNAs) represents an important mechanism of gene regulation, it is promising to explore this in relation to ZYP and cholestasis. AIM OF THE STUDY To confirm the anticholestatic effect of ZYP and to explore its potential biological mechanism. MATERIALS AND METHODS In this study, a cholestasis rat model was induced by α-naphthyl-isothiocyanate (ANIT, 50 mg/kg) and treated with ZYP (low dose: 0.6 g/kg, high dose: 1.2 g/kg). Serum biochemistry indices and liver histopathology were used to evaluate the model and efficacy, and miRNA sequencing was used to measure differences in miRNA expression in the liver between the control, model, low-dose ZYP, and high-dose ZYP groups. To verify the accuracy of sequencing results and explore the potential anti-cholestasis mechanism of ZYP, RT-PCR was used to identify differentially expressed miRNAs and their target genes. RESULTS Both high- and low-dose ZYP exhibited significant anticholestatic effects, with the high-dose showing better effects than low-dose ZYP. Additionally, four differentially expressed miRNAs, rno-miR-147, rno-miR-20b-5p, rno-miR-29b-3p, and rno-miR-3586-3p, were found to be upregulated in cholestasis and downregulated after ZYP intervention. Eight target genes of the above miRNAs, including ABCG8, CLOCK, PLEC, SLC4A2, NEB, ADAMTS12, TTN and FAM174B were inhibited in cholestatic rats, exhibiting up-regulated expression tendencies after ZYP intervention, and the expression tendencies were significant negatively correlated with serum biochemical indices. CONCLUSIONS ZYP can significantly reduce liver biochemical indices and improve liver tissue damage in cholestasis rats through the regulation of miRNA expression in the liver, producing a positive regulatory effect on bile excretion-related genes.
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Affiliation(s)
- Han Yu
- School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Chao Liu
- School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Jianfei Wang
- Department of Nephrology, South of Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Jun Han
- Department of Reader Service and Culture Education, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Fenghua Zhang
- School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xin Zhou
- School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yueqiang Wen
- School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
| | - Tao Shen
- School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
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Hao X, Zhou P, Yang Z, Yang T, Wang Y. The therapeutic effect of Huazhuojiedu decoction on precancerous lesions in a gastric cancer model via the regulation of lnc 517368. JOURNAL OF ETHNOPHARMACOLOGY 2022; 283:114635. [PMID: 34648901 DOI: 10.1016/j.jep.2021.114635] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Revised: 09/02/2021] [Accepted: 09/09/2021] [Indexed: 06/13/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Huazhuojiedu decoction, a Chinese herbal preparation, has been proven to be clinically effective in treating precancerous lesions in gastric cancer (PLGC). This formula is optimized from a classic formula called "Ganluxiaodu Dan." Although some experiments have shown that Huazhuojiedu decoction is effective against PLGC, the mechanism remains unclear. AIM OF THE STUDY To investigate the treatment of PLGC with Huazhuojiedu decoction from the perspective of lncRNA in vitro and in vivo. MATERIALS AND METHODS A PLGC rat model was prepared and randomly divided into a Huazhuojiedu decoction group (HG), a vitacoenzyme group (VG), a model group (MG), and a normal group (CG). Each group was given a corresponding concentration of medicine and distilled water for 10 weeks. The pathological changes in the gastric mucosa were observed by hematoxylin-eosin staining (HE). High-throughput sequencing was performed to detect the differentially expressed lncRNAs in the HG, MG, and CG. Quantitative real-time reverse transcription-polymerase chain reaction (RT-qPCR) was used to verify differentially expressed lncRNAs, and rat-human homology information was obtained from the University of California, Santa Cruz (UCSC) Genome Database. Human gastric mucosal epithelial cells (GES-1) were used to prepare precancerous lesions of gastric cancer cells (MC). A Huazhuojiedu decoction drug-containing serum was prepared to treat the MC cells. The effects of the Huazhuojiedu decoction and the lncRNA ENST00000517368 (lnc 517368) knockdown or overexpression on PLGC cell proliferation and apoptosis were evaluated in vitro using CCK-8, flow cytometry, and RT-qPCR. RESULTS The HE results showed that gastric mucosal pathology was significantly improved in the HG. High-throughput sequencing results showed that compared with the CG, 91 lncRNAs upregulated in the MG were restored and downregulated in the HG (P < 0.05), and 115 lncRNAs downregulated in the MG were restored and upregulated in the HG (P < 0.05). The results of RT-qPCR were consistent with the sequencing results. The differentially expressed genomic rat lncRNA ENSRNOT00000079699 is homologous to human lnc 517368. In cell experiments, high expression of lnc 517368 promoted proliferation and reduced apoptosis in PLGC cells, while the Huazhuojiedu decoction reduced the expression of lnc 517368 and improved cell morphology. CONCLUSIONS Huazhuojiedu decoction inhibited cell proliferation and promoted apoptosis in PLGC cells, and its effect may be partially dependent on the downregulation of lnc 517368.
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Affiliation(s)
- Xinyu Hao
- Hebei University of Chinese Medicine, Shijiazhuang, China.
| | - Pingping Zhou
- Hebei University of Chinese Medicine, Shijiazhuang, China
| | - Zeqi Yang
- Hebei University of Chinese Medicine, Shijiazhuang, China
| | - Tianxiao Yang
- Hebei University of Chinese Medicine, Shijiazhuang, China
| | - Yangang Wang
- The Third Affiliated Hospital of Beijing University of Chinese Medicine, Beijing, China.
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Li X, Wei S, Ma X, Li H, Jing M, Liu H, Niu S, Tong Y, Chen L, Wei Y, Ren S, Zhao Y. Huanglian Jiedu Decoction Exerts Antipyretic Effect by Inhibiting MAPK Signaling Pathway. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2021; 2021:2209574. [PMID: 35003291 PMCID: PMC8741374 DOI: 10.1155/2021/2209574] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Accepted: 12/15/2021] [Indexed: 01/17/2023]
Abstract
AIM The aim of this study was to explore the antipyretic effect and potential mechanism of Huanglian Jiedu Decoction (HLJDD) on LPS-induced fever in rats. MATERIALS AND METHODS The fever rat model was established by LPS. Anal temperature of rats was measured every 1 hour after modeling. TNF-α, IL-6, PGE2, and cAMP in rat serum or hypothalamus tissue were detected by ELISA kit. In order to explore the potential active ingredients and mechanism of antipyretic effect of HLJDD, we predicted the underlying antipyretic mechanism by using network pharmacology and then verified its mechanism by Western Blotting. RESULTS The results showed that HLJDD can alleviate LPS-induced fever in rats. The expression levels of TNF-α, IL-6, PGE2, and cAMP in the treatment group were significantly lower than those in the model group. Western Blotting results showed that the protein expression of p-ERK, p-JNK, and p-P38 was significantly inhibited. CONCLUSION The findings suggest that HLJDD has a good antipyretic effect on LPS-induced fever in rats, which may be closely related to the inhibition of MAPK signaling pathway.
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Affiliation(s)
- Xing Li
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
- Department of Pharmacy, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Shizhang Wei
- Department of Pharmacy, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Xiao Ma
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Haotian Li
- Department of Pharmacy, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Manyi Jing
- Department of Pharmacy, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Honghong Liu
- Integrated TCM and Western Medicine Department, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Shengqi Niu
- Department of Pharmacy, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
- Department of Pharmacy, Medical Supplies Centre of PLA General Hospital, Beijing, China
| | - Yuling Tong
- Department of Pharmacy, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Lisheng Chen
- Department of Pharmacy, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
- Department of Pharmacy, Hebei North University, Zhangjiakou, China
| | - Ying Wei
- Department of Pharmacy, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Sichen Ren
- Department of Pharmacy, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yanling Zhao
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
- Department of Pharmacy, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
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Xu W, Li B, Xu M, Yang T, Hao X. Traditional Chinese medicine for precancerous lesions of gastric cancer: A review. Biomed Pharmacother 2021; 146:112542. [PMID: 34929576 DOI: 10.1016/j.biopha.2021.112542] [Citation(s) in RCA: 74] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Revised: 12/12/2021] [Accepted: 12/13/2021] [Indexed: 01/30/2023] Open
Abstract
Gastric cancer (GC) is the fifth most common type of cancer and the third leading cause of death due to cancer worldwide. The gastric mucosa often undergoes many years of precancerous lesions of gastric cancer (PLGC) stages before progressing to gastric malignancy. Unfortunately, there are no effective Western drugs for patients with PLGC. In recent years, traditional Chinese medicine (TCM) has been proven effective in treating PLGC. Classical TCM formulas and chemical components isolated from some Chinese herbal medicines have been administered to treat PLGC, and the main advantage is their comprehensive intervention with multiple approaches and multiple targets. In this review, we focus on recent studies using TCM treatment for PLGC, including clinical observations and experimental research, with a focus on targets and mechanisms of drugs. This review provides some ideas and a theoretical basis for applying TCM to treat PLGC and prevent GC.
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Affiliation(s)
- Weichao Xu
- Hebei Hospital of Traditional Chinese Medicine, Shijiazhuang 050011, China; Hebei Key Laboratory of Integrated Traditional Chinese and Western Medicine Gastroenterology, Shijiazhuang 050011, China
| | - Bolin Li
- Hebei Hospital of Traditional Chinese Medicine, Shijiazhuang 050011, China; Hebei Key Laboratory of Integrated Traditional Chinese and Western Medicine Gastroenterology, Shijiazhuang 050011, China
| | - Miaochan Xu
- Hebei University of Chinese Medicine, Shijiazhuang 050200, China
| | - Tianxiao Yang
- Hebei University of Chinese Medicine, Shijiazhuang 050200, China
| | - Xinyu Hao
- Peking University Third Hospital, Beijing 100191, China.
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Tong Y, Jing M, Zhao X, Liu H, Wei S, Li R, Liu X, Wang M, Song H, Zhao Y. Metabolomic Study of Zuojin Pill in Relieving 1-Methyl-3-nitro-1-nitrosoguanidine-Induced Chronic Atrophic Gastritis. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2021; 2021:7004798. [PMID: 34956382 PMCID: PMC8709764 DOI: 10.1155/2021/7004798] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Accepted: 11/27/2021] [Indexed: 11/29/2022]
Abstract
The classic prescription Zuojin Pill (ZJP) shows a good therapeutic effect on chronic atrophic gastritis (CAG); it is of great significance to clarify its specific mechanism. Therefore, we explore the mechanism of ZJP on MNNG-induced CAG by integrating approaches. First of all, through the pathological changes of gastric tissue and the expression level of PGI and PGI/II in serum, the expression of inflammation-related factors was determined by RT-PCR to determine the efficacy. Then, UPLC-Q-TOF/MS was used for plasma and urine metabolomic analysis to screen the specific potential biomarkers and metabolic pathway of ZJP in ameliorating CAG and to explore its possible mechanism. ZJP significantly ameliorate the pathological injury of gastric tissue, increase levels of PGI and PGI/II, and reduce the expression level of proinflammatory factors. Through metabolomic analysis, 9 potential metabolic differences were identified and 6 related metabolic pathways were enriched. These findings indicate for the first time the potential mechanism of ZJP in improving CAG induced by MNNG and are of great significance to the clinical development and application of ZJP-related drugs.
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Affiliation(s)
- Yuling Tong
- Department of Pharmacy, Chinese PLA General Hospital, Beijing, China
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Manyi Jing
- Department of Pharmacy, Chinese PLA General Hospital, Beijing, China
| | - Xu Zhao
- Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Honghong Liu
- Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Shizhang Wei
- Department of Pharmacy, Chinese PLA General Hospital, Beijing, China
| | - Ruisheng Li
- Research Center for Clinical and Translational Medicine, Fifth Medical Center of PLA General Hospital of Chinese, Beijing, China
| | - Xia Liu
- Department of Pharmacy, Chinese PLA General Hospital, Beijing, China
| | - Min Wang
- Department of Pharmacy, Chinese PLA General Hospital, Beijing, China
| | - Hongtao Song
- Department of Pharmacy, 900 Hospital of the Joint Logistics Team, Fuzhou, China
| | - Yanling Zhao
- Department of Pharmacy, Chinese PLA General Hospital, Beijing, China
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
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Jiang JY, Liu DJ, Liu MX. The protective effect of NF-κB signaling pathway inhibitor PDTC on mice with chronic atrophic gastritis. Scand J Gastroenterol 2021; 56:1131-1139. [PMID: 34310252 DOI: 10.1080/00365521.2021.1953130] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE To understand the protective effect of NF-κB signaling pathway inhibitor pyrrolidinedithiocarbamate (PDTC) on mice with chronic atrophic gastritis (CAG). METHODS Helicobacter pylori (H. pylori) infection combined with high-salt diet was used to construct the CAG mouse model, and 100 or 200 mg/kg/day PDTC was intragastrically treated for 8 weeks. Then, hematoxylin and eosin (HE) and Alcian blue-periodic acid-Schiff (AB-PAS) staining were used to observe the pathology of gastric mucosa, while immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR), enzyme-linked immuno sorbent assay (ELISA) and western blotting were determined to detect the expression of related molecules. RESULTS The nuclear content of NF-κB p65 in the gastric mucosa of the CAG mice was increased accompanying by the structural disorder of the gastric mucosal epithelium, inflammatory cell infiltration, intestinal metaplasia, and increased MUC2 expression, but the symptoms were alleviated after PDTC treatment. In addition, the expressions of TNF-α, IL-1β, IL-6 and COX2 in the gastric mucosa and serum of CAG mice were higher than those control mice, which were reduced in CAG mice treated with either 100 or 200 mg/kg PDTC. Furthermore, 100 mg/kg and 200 mg/kg PDTC treatments reduced the serum PGE2 in CAG mice with the decreased PCNA and Ki-67 expression in gastric mucosa. The therapeutic effect of 200 mg/kg PDTC was significantly better than that of 100 mg/kg PDTC. CONCLUSION PDTC inhibited inflammation and the excessive proliferation of gastric mucosal epithelial cells, thereby exerting a potential therapeutic effect on CAG.
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Affiliation(s)
- Jun-Yan Jiang
- Department of Gastroenterology, Nan'an District People's Hospital of Chongqing, Chongqing, China
| | - Dai-Jiang Liu
- Department of Gastroenterology, Chongqing University Central Hospital (Chongqing Emergency Medical Center), Chongqing, China
| | - Mao-Xia Liu
- Outpatient Department, Chongqing University Central Hospital (Chongqing Emergency Medical Center), Chongqing, China
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Wang K, Miao X, Kong F, Huang S, Mo J, Jin C, Zheng Y. Integrating Network Pharmacology and Experimental Verification to Explore the Mechanism of Effect of Zuojin Pills in Pancreatic Cancer Treatment. DRUG DESIGN DEVELOPMENT AND THERAPY 2021; 15:3749-3764. [PMID: 34511884 PMCID: PMC8427689 DOI: 10.2147/dddt.s323360] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Accepted: 08/17/2021] [Indexed: 12/12/2022]
Abstract
Background and Aim Pancreatic cancer is one of the most malignant tumors worldwide. Zuojin pills (ZJP), a traditional Chinese medicine (TCM) formula, which can treat a variety of cancers. However, the active compounds present in ZJP and the potential mechanisms through which ZJP acts against pancreatic cancer have not been thoroughly investigated. Methods Data on pancreatic cancer-related genes, bioactive compounds, and potential targets of ZJP were downloaded from public databases. Bioinformatics analysis, including protein–protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, was conducted to identify important components, potential targets, and signaling pathways through which ZJP affects pancreatic cancer. The results of this analysis were verified by in vitro experiments. Results The network pharmacology analysis results showed that 41 compounds and 130 putative target genes of ZJP were associated with anti-pancreatic cancer effects. ZJP may exert its inhibitory effects against pancreatic cancer by acting on key targets such as JUN, TP53, and MAPK1. Moreover, KEGG analysis indicated that the anti-pancreatic cancer effect of ZJP was mediated by multiple pathways, such as the PI3K-AKT, IL-17, TNF, HIF-1, and P53 signaling pathways. Among these, the PI3K-AKT signaling pathway, which included the highest number of enriched genes, may play a more important role in treating pancreatic cancer. The in vitro results showed that ZJP significantly inhibits the cell cycle and cell proliferation through the PI3K/AKT/caspase pathway and that it can induce apoptosis of pancreatic cancer cells, consistent with the results predicted by network pharmacological methods. Conclusion This study preliminarily investigated the pharmacological effects of ZJP, which appear to be mediated by multiple compounds, targets and pathways, and its potential therapeutic effect on pancreatic cancer. Importantly, our work provides a promising approach for the identification of compounds in TCM and the characterization of therapeutic mechanisms.
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Affiliation(s)
- Kunpeng Wang
- Department of General Surgery, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, 318000, Zhejiang, People's Republic of China
| | - Xiongying Miao
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, People's Republic of China
| | - Fanhua Kong
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, People's Republic of China
| | - Siqi Huang
- Department of Integrated Traditional Chinese & Western Medicine, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, People's Republic of China
| | - Jinggang Mo
- Department of General Surgery, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, 318000, Zhejiang, People's Republic of China
| | - Chong Jin
- Department of General Surgery, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, 318000, Zhejiang, People's Republic of China
| | - Yanwen Zheng
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, People's Republic of China
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