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Yao QX, Li ZY, Kang HL, He X, Kang M. Effect of acacetin on inhibition of apoptosis in Helicobacter pylori-infected gastric epithelial cell line. World J Gastrointest Oncol 2024; 16:3624-3634. [PMID: 39171164 PMCID: PMC11334024 DOI: 10.4251/wjgo.v16.i8.3624] [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: 04/09/2024] [Revised: 05/15/2024] [Accepted: 05/31/2024] [Indexed: 08/07/2024] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori) infection can cause extensive apoptosis of gastric epithelial cells, serving as a critical catalyst in the progression from chronic gastritis, gastrointestinal metaplasia, and atypical gastric hyperplasia to gastric carcinoma. Prompt eradication of H. pylori is paramount for ameliorating the pathophysiological conditions associated with chronic inflammation of the gastric mucosa and the primary prevention of gastric cancer. Acacetin, which has multifaceted pharmacological activities such as anti-cancer, anti-inflammatory, and antioxidative properties, has been extensively investigated across various domains. Nevertheless, the impact and underlying mechanisms of action of acacetin on H. pylori-infected gastric mucosal epithelial cells remain unclear. AIM To explore the defensive effects of acacetin on apoptosis in H. pylori-infected GES-1 cells and to investigate the underlying mechanisms. METHODS GES-1 cells were treated with H. pylori and acacetin in vitro. Cell viability was assessed using the CCK-8 assay, cell mortality rate via lactate dehydrogenase assay, alterations in cell migration and healing capacities through the wound healing assay, rates of apoptosis via flow cytometry and TUNEL staining, and expression levels of apoptosis-associated proteins through western blot analysis. RESULTS H. pylori infection led to decreased GES-1 cell viability, increased cell mortality, suppressed cell migration, increased rate of apoptosis, increased expressions of Bax and cle-caspase3, and decreased Bcl-2 expression. Conversely, acacetin treatment enhanced cell viability, mitigated apoptosis induced by H. pylori infection, and modulated the expression of apoptosis-regulatory proteins by upregulating Bcl-2 and downregulating Bax and cleaved caspase-3. CONCLUSION Acacetin significantly improved GES-1 cell viability and inhibited apoptosis in H. pylori-infected GES-1 cells, thereby exerting a protective effect on gastric mucosal epithelial cells.
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Affiliation(s)
- Qi-Xi Yao
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China
| | - Zi-Yu Li
- Department of Orthopaedics, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China
| | - Hou-Le Kang
- Department of Emergency, Luzhou People’s Hospital, Luzhou 646000, Sichuan Province, China
| | - Xin He
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China
| | - Min Kang
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, 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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Kabieva S, Zhumanazarova G, Zhaslan R, Zhumabayeva G, Ukhov A, Fedorishin D, Gubankov A, Tarikhov F, Yerkhan O, Irina K, Yerkassov R, Bakibaev A. Obtaining New Biocompatible Composite Materials with Antibacterial Properties Based on Diatomite and Biologically Active Compounds. Molecules 2024; 29:1608. [PMID: 38611887 PMCID: PMC11013188 DOI: 10.3390/molecules29071608] [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: 02/16/2024] [Revised: 03/24/2024] [Accepted: 03/28/2024] [Indexed: 04/14/2024] Open
Abstract
This study aimed to create new composite materials based on diatomite-a non-organic porous compound-through its surface modification with bioactive organic compounds, both synthetic and natural. Chloramphenicol, tetrahydroxymethylglycoluril and betulin were used as modifying substances. Composite materials were obtained by covering the diatomite surface with bioactive substance compounds as a solution and material dispersion in it. The materials were characterized by IR spectroscopy, SEM and X-ray photoelectron spectroscopy. For the biocomposites, the hemolytic effect, plasma proteins' adsorption on the surface and the antibacterial activity of the obtained materials were studied. Results show that the obtained materials are promising for medicine and agriculture.
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Affiliation(s)
- Saule Kabieva
- Department of Chemical Technology and Ecology, Karaganda Industrial University, Temirtau 101400, Kazakhstan; (S.K.); (R.Z.)
| | - Gaziza Zhumanazarova
- Department of Chemical Technology and Ecology, Karaganda Industrial University, Temirtau 101400, Kazakhstan; (S.K.); (R.Z.)
| | - Rymgul Zhaslan
- Department of Chemical Technology and Ecology, Karaganda Industrial University, Temirtau 101400, Kazakhstan; (S.K.); (R.Z.)
| | - Gulistan Zhumabayeva
- Faculty of Natural Sciences, L.N. Gumilyov Eurasian National University, St. Satbaeva 2, Almaty District, Astana 010000, Kazakhstan; (G.Z.); (O.Y.); (R.Y.)
| | - Arthur Ukhov
- Chemical Faculty, National Research Tomsk State University, Arkady Ivanov St. 49, Tomsk 634028, Russia; (A.U.); (D.F.); (A.G.); (F.T.); (K.I.); (A.B.)
| | - Dmitry Fedorishin
- Chemical Faculty, National Research Tomsk State University, Arkady Ivanov St. 49, Tomsk 634028, Russia; (A.U.); (D.F.); (A.G.); (F.T.); (K.I.); (A.B.)
| | - Alexander Gubankov
- Chemical Faculty, National Research Tomsk State University, Arkady Ivanov St. 49, Tomsk 634028, Russia; (A.U.); (D.F.); (A.G.); (F.T.); (K.I.); (A.B.)
| | - Farkhad Tarikhov
- Chemical Faculty, National Research Tomsk State University, Arkady Ivanov St. 49, Tomsk 634028, Russia; (A.U.); (D.F.); (A.G.); (F.T.); (K.I.); (A.B.)
| | - Ordabay Yerkhan
- Faculty of Natural Sciences, L.N. Gumilyov Eurasian National University, St. Satbaeva 2, Almaty District, Astana 010000, Kazakhstan; (G.Z.); (O.Y.); (R.Y.)
| | - Kurzina Irina
- Chemical Faculty, National Research Tomsk State University, Arkady Ivanov St. 49, Tomsk 634028, Russia; (A.U.); (D.F.); (A.G.); (F.T.); (K.I.); (A.B.)
| | - Rakhmetulla Yerkassov
- Faculty of Natural Sciences, L.N. Gumilyov Eurasian National University, St. Satbaeva 2, Almaty District, Astana 010000, Kazakhstan; (G.Z.); (O.Y.); (R.Y.)
| | - Abdigali Bakibaev
- Chemical Faculty, National Research Tomsk State University, Arkady Ivanov St. 49, Tomsk 634028, Russia; (A.U.); (D.F.); (A.G.); (F.T.); (K.I.); (A.B.)
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Guo C, Wan L, Li C, Wen Y, Pan H, Zhao M, Wang J, Ma X, Nian Q, Tang J, Zeng J. Natural products for gastric carcinoma prevention and treatment: Focus on their antioxidant stress actions in the Correa's cascade. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 123:155253. [PMID: 38065034 DOI: 10.1016/j.phymed.2023.155253] [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: 08/26/2023] [Revised: 11/15/2023] [Accepted: 12/01/2023] [Indexed: 01/17/2024]
Abstract
BACKGROUND Correa's cascade is a pathological process beginning from gastritis to gastric precancerous lesions, and finally to gastric carcinoma (GC). While the pathogenesis of GC remains unclear, oxidative stress plays a prominent role throughout the entire Correa's cascade process. Studies have shown that some natural products (NPs) could halt and even reverse the development of the Correa's cascade by targeting oxidative stress. METHODS To review the effects and mechanism by which NPs inhibit the Correa's cascade through targeting oxidative stress, data were collected from PubMed, Embase, Web of Science, ScienceDirect, and China National Knowledge Infrastructure databases from initial establishment to April 2023. NPs were classified and summarized by their mechanisms of action. RESULTS NPs, such as terpenoid, polyphenols and alkaloids, exert multistep antioxidant stress effects on the Correa's cascade. These effects include preventing gastric mucosal inflammation (stage 1), reversing gastric precancerous lesions (stage 2), and inhibiting gastric carcinoma (stage 3). NPs can directly impact the conversion of gastritis to GC by targeting oxidative stress and modulating signaling pathways involving IL-8, Nrf2, TNF-α, NF-κB, and ROS/MAPK. Among which polyphenols have been studied more and are of high research value. CONCLUSIONS NPs display a beneficial multi-step action on the Correa's cascade, and have potential value for clinical application in the prevention and treatment of gastric cancer by regulating the level of oxidative stress.
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Affiliation(s)
- Cui Guo
- Department of Oncology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China; TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China
| | - Lina Wan
- Department of Oncology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China
| | - Chengen Li
- Department of Oncology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China
| | - Yueqiang Wen
- School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Huafeng Pan
- Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China
| | - Maoyuan Zhao
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China
| | - Jundong Wang
- Department of Oncology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China
| | - Xiao Ma
- State Key Laboratory of Southwestern Chinese Medicine Resources,Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
| | - Qing Nian
- Department of Transfusion, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 610072, China.
| | - Jianyuan Tang
- Department of Oncology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China; TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China.
| | - Jinhao Zeng
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China; Department of gastroenterology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China.
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Tang W, Guan M, Li Z, Pan W, Wang Z. A2BR facilitates the pathogenesis of H. pylori-associated GU by inducing oxidative stress through p38 MAPK phosphorylation. Heliyon 2023; 9:e21004. [PMID: 38027590 PMCID: PMC10660004 DOI: 10.1016/j.heliyon.2023.e21004] [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: 05/19/2023] [Revised: 09/25/2023] [Accepted: 10/12/2023] [Indexed: 12/01/2023] Open
Abstract
Gastric ulcers significantly impact the quality of life of patients, the pathogenesis of which is closely associated with Helicobacter pylori (HP) infection. Oxidative stress is involved in the pathological mechanism of gastric ulcers. Recently, adenosine A2B Receptor (A2BR) was reported to activate the p38MAPK pathway. However, the role of A2BR in gastric ulcers remains unknown. In the present study, the biological function of A2BR in HP-induced gastric ulcers was investigated to explore novel targets for gastric ulcers. GES-1 cells were infected with HP, followed by incubation with 10 μM BAY60-6583 (A2BR agonist) and 25 nM PSB1115 (A2BR antagonist). In HP-infected GES-1 cells, an increased apoptotic rate, enhanced migration ability, excessive release of reactive oxygen species (ROS), increased malondialdehyde (MDA) levels, and decreased superoxide dismutase (SOD) activity were observed, accompanied by the activation of p38MAPK signaling, which were dramatically aggravated by BAY60-6583 and alleviated by PSB1115. In animal experiments, rats were treated with 2 mg/kg BAY60-6583 and 10 mg/kg PSB1115, followed by gastric ulcer modeling 30 min later. In HP-infected rats, increased ulcer area, elevated pepsin activity, increased hematoxylin and eosin (HE) pathological scores, increased MDA levels, and decreased SOD activity were observed, which were further aggravated by BAY60-6583 and ameliorated by PSB1115. Finally, the effects of A2BR activation on apoptosis, migration, oxidative stress, and p38MAPK signaling in HP-infected GES-1 cells were reversed by an inhibitor of the p38MAPK pathway. Collectively, A2BR facilitated the pathogenesis of HP-induced gastric ulcers by inducing oxidative stress through p38MAPK activation.
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Affiliation(s)
- Weihong Tang
- Department of Gastroenterology. Hangzhou Children's Hospital, No.195, Wenhui Road, Xiacheng District, Hangzhou, Zhejiang, 310014, China
| | - Minchang Guan
- Department of Pediatrics. Hangzhou Hospital of Traditional Chinese Medicine, No. 1630, Huanding Road, Hangzhou, Zhejiang, 310014, China
| | - Ze Li
- Department of Gastroenterology. Hangzhou Children's Hospital, No.195, Wenhui Road, Xiacheng District, Hangzhou, Zhejiang, 310014, China
| | - Wei Pan
- Department of Gastroenterology. Hangzhou Children's Hospital, No.195, Wenhui Road, Xiacheng District, Hangzhou, Zhejiang, 310014, China
| | - Zhongmin Wang
- Department of Gastroenterology. Hangzhou Children's Hospital, No.195, Wenhui Road, Xiacheng District, Hangzhou, Zhejiang, 310014, China
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Zhuang K, Tang H, Guo H, Yuan S. Geraniol prevents Helicobacterium pylori-induced human gastric cancer signalling by enhancing peroxiredoxin-1 expression in GES-1 cells. Microb Pathog 2023; 174:105937. [PMID: 36496058 DOI: 10.1016/j.micpath.2022.105937] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 11/30/2022] [Accepted: 12/06/2022] [Indexed: 12/14/2022]
Abstract
Helicobacter pylori (H. pylori), a gram-negative bacterial microbiological carcinogen, has been identified as the leading jeopardy feature for developing human gastric cancer (GC). As a result, inhibiting H. pylori growth has been identified as an effective and critical technique for preventing GC development. In this study, geraniol inhibits H. pylori-induced gastric carcinogen signalling in human gastric epithelial cells (GES-1). Geraniol prevents cytotoxicity, ROS and apoptosis in H. pylori-induced GES-1 cells. Furthermore, geraniol protects against H. -induced antioxidant depletion caused by malondialdehyde, damage of reactive DNA and nuclear fragmentation. Geraniol significantly reduced the expression of phosphorylated mitogen activated protein kinases (MAPKs) proteins such as p38 MAPK, extracellular signal-regulated kinase-1 (ERK1), c-Jun N-terminal kinase (c-JNK), tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and cyclooxygenase-2 (COX-2) in GES-1 infected with H. pylori. Furthermore, geraniol increased the antioxidant protein peroxiredoxin-1 (Prdx-1) in H. pylori-infected cells. Geraniol thus protects H. pylori-concomitant infection, and its resistance may be a possible method in preventing gastric cancer caused by H. pylori.
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Affiliation(s)
- Kun Zhuang
- Department of Gastroenterology, Xi'an Central Hospital, Xi'an, 710003, China.
| | - Hailing Tang
- Department of Gastroenterology, Xi'an Central Hospital, Xi'an, 710003, China
| | - Hanqing Guo
- Department of Gastroenterology, Xi'an Central Hospital, Xi'an, 710003, China
| | - Shanshan Yuan
- Department of Gastroenterology, Xi'an Central Hospital, Xi'an, 710003, China
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Lu Y, Li SY, Lou H. Patchouli alcohol protects against myocardial ischaemia-reperfusion injury by regulating the Notch1/Hes1 pathway. PHARMACEUTICAL BIOLOGY 2022; 60:949-957. [PMID: 35588098 PMCID: PMC9122376 DOI: 10.1080/13880209.2022.2064881] [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: 11/28/2021] [Revised: 03/14/2022] [Accepted: 03/27/2022] [Indexed: 06/15/2023]
Abstract
CONTEXT Patchouli alcohol (PA) has protective effects on cerebral ischaemia/reperfusion (I/R) injury, but its efficacy on myocardial ischaemia-reperfusion (MI/R) has yet to be addressed. OBJECTIVE To examine the therapeutic effect of PA on myocardial ischaemia-reperfusion (I/R) injury. MATERIALS AND METHODS C57BL/6 male mice were randomly divided into sham, MI/R, MI/R + PA-10, MI/R + PA-20 and MI/R + PA-40 groups. In vivo MI/R model was established by ligating the anterior descending coronary artery of the heart. In vitro stimulated IR cell model was constructed by using the rat cardiomyocyte H9C2 cell line. Mice in the treatment groups were intraperitoneally injected with PA (10, 20, 40 mg/kg) for 30 days then subjected to surgery, and cells in the experimental group were pre-treated with PA (1, 10 or 100 μmol/L). After treatment, mouse heart function, myocardial injury markers, myocardial infarction and Notch1/Hes1 expression, endoplasmic reticulum stress markers, and apoptosis-related proteins were determined. RESULTS In vivo, PA treatment improved hemodynamic parameter changes and myocardial enzymes, increased the left ventricular ejection fraction and left ventricular fractional shortening, reduced the left ventricular end-systolic diameter and inhibited CK-MB, cTnI and cTnT levels. In addition, PA attenuated myocardial tissue damage and apoptosis. PA treatment elevated Notch1, NICD and Hes1 levels and suppressed the levels of ATF4, p-PERK/PERK, and cleaved caspase-3/caspase-3 in vitro and in vivo. DISCUSSION AND CONCLUSION PA protects against MI/R, possibly by modulating ER stress, apoptosis and the Notch1/Hes1 signalling pathways. These findings indicate that PA may be a promising candidate for treating ischaemic heart diseases.
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Affiliation(s)
- Ying Lu
- Electrocardiogram room of Department of Functional Examination, Tongde Hospital of Zhejiang Province, Hangzhou, China
| | - Shou-ye Li
- College of Pharmacy, Hangzhou Medical College, Hangzhou, China
| | - Hui Lou
- Electrocardiogram room of Department of Functional Examination, Tongde Hospital of Zhejiang Province, Hangzhou, China
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The Anti-Inflammatory Effect of Callicarpa nudiflora Extract on H. Pylori-Infected GES-1 Cells through the Inhibition of ROS/NLRP3/Caspase-1/IL-1β Signaling Axis. CANADIAN JOURNAL OF INFECTIOUS DISEASES AND MEDICAL MICROBIOLOGY 2022; 2022:5469236. [PMID: 35873363 PMCID: PMC9307406 DOI: 10.1155/2022/5469236] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 02/21/2022] [Accepted: 05/06/2022] [Indexed: 11/23/2022]
Abstract
Helicobacter pylori (H. pylori) is the main pathogenic factor of gastric cancer, chronic gastritis, and other gastric diseases. It has been found that Callicarpa nudiflora (CN) as an air-dried leaf extract has a broad-spectrum antibacterial effect. This study aims to examine the effect of CN on H. pylori-infected GES-1 cells in vitro and elucidate its underlying mechanism by extracting active ingredients from air-dried leaves. GES-1 cells were cocultured with HPSS1 at MOI = 100 : 1 and treated with different concentrations of CN (100 and 200 μg/ml). Results showed that CN can significantly reduce cellular LDH leakage and attenuate H. pylori-induced cell apoptosis and ROS production in GSE-1 cells, so as to protect gastric epithelial cells from damage by H. pylori. CN can also inhibit the secretion of inflammatory factors, such as TNF-α, IL-1β, IL-6, and IL-8. After CN treatment, the expression levels of active caspase-1, PYCARD, and NLRP3 were remarkably decreased in the treatment groups compared with the model group. To sum up, CN is highly protective against H. pylori-induced cell damage and apoptosis; CN can depress NLRP3 inflammasome activation and ROS production via the ROS/NLRP3/caspase-1/IL-1β signaling axis to suppress H. pylori-triggered inflammatory response and pyroptosis.
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In Vitro Activity of the Arylaminoartemisinin GC012 against Helicobacter pylori and Its Effects on Biofilm. Pathogens 2022; 11:pathogens11070740. [PMID: 35889986 PMCID: PMC9324866 DOI: 10.3390/pathogens11070740] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Revised: 06/20/2022] [Accepted: 06/27/2022] [Indexed: 12/17/2022] Open
Abstract
This study evaluated the in vitro activity of the arylaminoartemisinin GC012, readily obtained from dihydroartemisinin (DHA), against clinical strains of Helicobacter pylori (H. pylori) with different antibiotic susceptibilities in the planktonic and sessile state. The activity was assessed in terms of bacteriostatic and bactericidal potential. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined by the broth microdilution method. After treatment with GC012, all bacterial strains showed significantly lower MIC and MBC values compared to those of DHA. The effect of combination of GC012 with antibiotics was examined using the checkerboard method. GC012 displayed synergistic interactions with metronidazole, clarithromycin, and amoxicillin in all the strains. The antibiofilm activity was evaluated via crystal violet staining, AlamarBlue® assay, colony-forming unit count, and fluorescence microscopy. At ½ MIC and ¼ MIC concentration, both GC012 and DHA inhibited biofilm formation, but only GC012 showed a minimal biofilm eradication concentration (MBEC) on mature biofilm. Furthermore, both compounds induced structural changes in the bacterial membrane, as observed by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). It is thereby demonstrated that GC012 has the potential to be efficacious against H. pylori infection.
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Gossypol from Gossypium spp. Inhibits Helicobacter pylori Clinical Strains and Urease Enzyme Activity: Bioactivity and Safety Assessments. Sci Pharm 2022. [DOI: 10.3390/scipharm90020029] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/10/2022] Open
Abstract
This study investigates the inhibitory activities of gossypol, a natural polyphenolic compound from Gossypium spp., against Helicobacter pylori (HP) clinical strains and a urease enzyme that plays a key role in the pathogenesis of HP. Gossypol was detected to exhibit a bacteriostatic action against all the HP strains tested with minimum inhibitory concentration (MIC) values ranging from 3.51 to 4.14 µg/mL. The activity of HP urease (HPU) was efficiently impeded by gossypol with a 50% inhibitory concentration (IC50) value of 3.3 µM using an Electrospray Ionization–Mass Spectrometry (ESI-MS)-based method. The in vitro cytotoxicity assay showed no significant cytotoxic properties of gossypol against human gastric epithelial cells. Additionally, molecular docking studies were performed to assess the binding mode and the molecular interactions of gossypol with HPU with a binding affinity value of −8.1 kcal/mol compared with an HPU–acetohydroxamic acid (a standard urease inhibitor) docking complex (–6.1 kcal/mol). The overall results reveal that gossypol might help fight against HP infection by two mechanisms of action: inhibition of the growth of HP and inhibition of urease.
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Junren C, Xiaofang X, Mengting L, Qiuyun X, Gangmin L, Huiqiong Z, Guanru C, Xin X, Yanpeng Y, Fu P, Cheng P. Pharmacological activities and mechanisms of action of Pogostemon cablin Benth: a review. Chin Med 2021; 16:5. [PMID: 33413544 PMCID: PMC7791836 DOI: 10.1186/s13020-020-00413-y] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Revised: 11/18/2020] [Accepted: 12/11/2020] [Indexed: 02/07/2023] Open
Abstract
Patchouli ("Guanghuoxiang") or scientifically known as Pogostemon cablin Benth, belonging to the family Lamiaceae, has been used in traditional Chinse medicine (TCM) since the time of the Eastern Han dynasty. In TCM theory, patchouli can treat colds, nausea, fever, headache, and diarrhea. Various bioactive compounds have been identified in patchouli, including terpenoids, phytosterols, flavonoids, organic acids, lignins, glycosides, alcohols, pyrone, and aldehydes. Among the numerous compounds, patchouli alcohol, β-patchoulene, patchoulene epoxide, pogostone, and pachypodol are of great importance. The pharmacological impacts of these compounds include anti-peptic ulcer effect, antimicrobial effect, anti-oxidative effect, anti-inflammatory effect, effect on ischemia/reperfusion injury, analgesic effect, antitumor effect, antidiabetic effect, anti-hypertensive effect, immunoregulatory effect, and others.For this review, we examined publications from the previous five years collected from PubMed, Web of Science, Springer, and the Chinese National Knowledge Infrastructure databases. This review summarizes the recent progress in phytochemistry, pharmacology, and mechanisms of action and provides a reference for future studies focused on clinical applications of this important plant extract.
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Affiliation(s)
- Chen Junren
- Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China
- State Key Laboratory of Traditional Chinese Medicine Resources in Southwest China, Chengdu, 610075, China
| | - Xie Xiaofang
- Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China
- State Key Laboratory of Traditional Chinese Medicine Resources in Southwest China, Chengdu, 610075, China
| | - Li Mengting
- Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China
- State Key Laboratory of Traditional Chinese Medicine Resources in Southwest China, Chengdu, 610075, China
| | - Xiong Qiuyun
- Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China
- State Key Laboratory of Traditional Chinese Medicine Resources in Southwest China, Chengdu, 610075, China
| | - Li Gangmin
- Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China
- State Key Laboratory of Traditional Chinese Medicine Resources in Southwest China, Chengdu, 610075, China
| | - Zhang Huiqiong
- Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China
- State Key Laboratory of Traditional Chinese Medicine Resources in Southwest China, Chengdu, 610075, China
| | - Chen Guanru
- Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China
- State Key Laboratory of Traditional Chinese Medicine Resources in Southwest China, Chengdu, 610075, China
| | - Xu Xin
- Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China
- State Key Laboratory of Traditional Chinese Medicine Resources in Southwest China, Chengdu, 610075, China
| | - Yin Yanpeng
- Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China
- State Key Laboratory of Traditional Chinese Medicine Resources in Southwest China, Chengdu, 610075, China
| | - Peng Fu
- Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China.
- State Key Laboratory of Traditional Chinese Medicine Resources in Southwest China, Chengdu, 610075, China.
- West China School of Pharmacy, Sichuan University, 17 South Renmin Rd, 610065, Chengdu, China.
| | - Peng Cheng
- Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China.
- State Key Laboratory of Traditional Chinese Medicine Resources in Southwest China, Chengdu, 610075, China.
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, 37 Shierqiao Road, Jinniu District, Chengdu, 611137, China.
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12
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Zhang Y, Sun J, Dong Y, Shen X, Zhang Z. Vicenin-2 inhibits the Helicobacterium pylori infection associated gastric carcinogenic events through modulation of PI3K/AKT and Nrf2 signaling in GES-1 cells. J Biochem Mol Toxicol 2020; 35:e22680. [PMID: 33325628 DOI: 10.1002/jbt.22680] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Revised: 10/04/2020] [Accepted: 11/26/2020] [Indexed: 12/12/2022]
Abstract
Helicobacter pylori (H. pylori), a microbial carcinogen of Gram-negative bacteria, has been recognized to be the highest risk factor for the growth of human gastric cancer (GC). Therefore, the inhibition of the growth rate of H. pylori has been considered an effective vital strategy to prevent GC development. This study highlights the inhibitory effect of vicenin-2 against H. pylori-induced gastric carcinogen signaling in human gastric epithelial cells (GES-1). In vitro cytotoxicity studies reported that 40 µM of vicenin-2 remarkably protects the gastric cells and this concentration shows 85% cell viability also does not produce toxicity. In addition, vicenin-2 prevents H. pylori-infected increased depletion of antioxidants mediated by reactive oxygen species generation, DNA damage, malondialdehyde, and nuclear fragmentation. Here, we noticed that vicenin-2 remarkably suppressed the expression range of the phosphorylated form of phosphatidylinositol 3-kinase/protein kinase B, phosphorylated p38 kinases, phosphorylated extracellular signal-regulated kinase-1, phosphorylated c-Jun N-terminal kinase, tumor necrosis factor-α, interleukin-6, cyclooxygenase-2 in GES-1 infected with H. pylori. Moreover, we observed that vicenin-2 enhanced the antioxidants protein nuclear factor erythroid factor-2 and phosphatase and tensin homolog expression in H. pylori-infected cells. Thus, vicenin-2 prevents the H. pylori-associated infection, and its resistance might be a potential strategy in preventing GC induced by H. pylori.
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Affiliation(s)
- Yifeng Zhang
- Department of Gastroenterology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Jing Sun
- Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yu Dong
- Department of Gastroenterology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Xiaoran Shen
- Department of Gastroenterology, Nantong First People's Hospital, Nantong, China
| | - Zhenyu Zhang
- Department of Gastroenterology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
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13
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Pogostemon cablin Triggered ROS-Induced DNA Damage to Arrest Cell Cycle Progression and Induce Apoptosis on Human Hepatocellular Carcinoma In Vitro and In Vivo. Molecules 2020; 25:molecules25235639. [PMID: 33266043 PMCID: PMC7731310 DOI: 10.3390/molecules25235639] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2020] [Revised: 11/27/2020] [Accepted: 11/27/2020] [Indexed: 12/18/2022] Open
Abstract
The purpose of the study was to elucidate the anti-hepatoma effects and mechanisms of Pogostemon cablin essential oils (PPa extract) in vitro and in vivo. PPa extract exhibited an inhibitory effect on hepatocellular carcinoma (HCC) cells and was less cytotoxic to normal cells, especially normal liver cells, than it was to HCC cells, exerting a good selective index. Additionally, PPa extract inhibited HCC cell growth by blocking the cell cycle at the G0/G1 phase via p53 dependent or independent pathway to down regulated cell cycle regulators. Moreover, PPa extract induced the FAS-FASL-caspase-8 system to activate the extrinsic apoptosis pathway, and it increased the bax/bcl-2 ratio and reduced ΔΨm to activate the intrinsic apoptosis pathway that might be due to lots of reactive oxygen species (ROS) production which was induced by PPa extract. In addition, PPa extract presented to the potential to act synergistically with sorafenib to effectively inhibit HCC cell proliferation through the Akt/mTOR pathway and reduce regrowth of HCC cells. In an animal model, PPa extract suppressed HCC tumor growth and prolonged lifespan by reducing the VEGF/VEGFR axis and inducing tumor cell apoptosis in vivo. Ultimately, PPa extract demonstrated nearly no or low system-wide, physiological, or pathological toxicity in vivo. In conclusion, PPa extract effectively inhibited HCC cell growth through inducing cell cycle arrest and activating apoptosis in vitro and in vivo. Furthermore, PPa extract exhibits less toxicity toward normal cells and organs than it does toward HCC cells, which might lead to fewer side effects in clinical applications. PPa extract may be developed into a clinical drug to suppress tumor growth or functional food to prevent HCC initiation or chemoprotection of HCC recurrence.
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He Y, Wang C, Zhang X, Lu X, Xing J, Lv J, Guo M, Huo X, Liu X, Lu J, Du X, Li C, Chen Z. Sustained Exposure to Helicobacter pylori Lysate Inhibits Apoptosis and Autophagy of Gastric Epithelial Cells. Front Oncol 2020; 10:581364. [PMID: 33194715 PMCID: PMC7658535 DOI: 10.3389/fonc.2020.581364] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Accepted: 09/30/2020] [Indexed: 12/12/2022] Open
Abstract
Helicobacter pylori is designated as a class I carcinogen of human gastric cancer following long-term infection. During this process, H. pylori bacteria persist in proliferation and death, and release bacterial components that come into contact with gastric epithelial cells and regulate host cell function. However, the impact of long-term exposure to H. pylori lysate on the pathological changes of gastric cells is not clear. In this study, we aimed to investigate the regulation and mechanisms involved in gastric cell dysfunction following continuous exposure to H. pylori lysate. We co-cultured gastric cell lines GES-1 and MKN-45 with H. pylori lysate for 30 generations, and we found that sustained exposure to H. pylori lysate inhibited GES-1 cell invasion, migration, autophagy, and apoptosis, while it did not inhibit MKN-45 cell invasion or migration. Furthermore, Mongolian gerbils infected with H. pylori ATCC 43504 strains for 90 weeks confirmed the in vitro results. The clinical and in vitro data indicated that sustained exposure to H. pylori lysate inhibited cell apoptosis and autophagy through the Nod1-NF-κB/MAPK-ERK/FOXO4 signaling pathway. In conclusion, sustained exposure to H. pylori lysate promoted proliferation of gastric epithelial cells and inhibited autophagy and apoptosis via Nod1-NF-κB/MAPK-ERK/FOXO4 signaling pathway. In the process of H. pylori-induced gastric lesions, H. pylori lysate plays as an "accomplice" to carcinogenesis.
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Affiliation(s)
- Yang He
- School of Basic Medical Sciences, Capital Medical University, Beijing Key Laboratory of Cancer Invasion & Metastasis Research, Beijing, China
| | - Cunlong Wang
- School of Basic Medical Sciences, Capital Medical University, Beijing Key Laboratory of Cancer Invasion & Metastasis Research, Beijing, China
| | - Xiulin Zhang
- School of Basic Medical Sciences, Capital Medical University, Beijing Key Laboratory of Cancer Invasion & Metastasis Research, Beijing, China
| | - Xuancheng Lu
- Laboratory Animal Center, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Jin Xing
- Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control, Beijing, China
| | - Jianyi Lv
- School of Basic Medical Sciences, Capital Medical University, Beijing Key Laboratory of Cancer Invasion & Metastasis Research, Beijing, China
| | - Meng Guo
- School of Basic Medical Sciences, Capital Medical University, Beijing Key Laboratory of Cancer Invasion & Metastasis Research, Beijing, China
| | - Xueyun Huo
- School of Basic Medical Sciences, Capital Medical University, Beijing Key Laboratory of Cancer Invasion & Metastasis Research, Beijing, China
| | - Xin Liu
- School of Basic Medical Sciences, Capital Medical University, Beijing Key Laboratory of Cancer Invasion & Metastasis Research, Beijing, China
| | - Jing Lu
- School of Basic Medical Sciences, Capital Medical University, Beijing Key Laboratory of Cancer Invasion & Metastasis Research, Beijing, China
| | - Xiaoyan Du
- School of Basic Medical Sciences, Capital Medical University, Beijing Key Laboratory of Cancer Invasion & Metastasis Research, Beijing, China
| | - Changlong Li
- School of Basic Medical Sciences, Capital Medical University, Beijing Key Laboratory of Cancer Invasion & Metastasis Research, Beijing, China
| | - Zhenwen Chen
- School of Basic Medical Sciences, Capital Medical University, Beijing Key Laboratory of Cancer Invasion & Metastasis Research, Beijing, China
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15
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Lee HS, Lee J, Smolensky D, Lee SH. Potential benefits of patchouli alcohol in prevention of human diseases: A mechanistic review. Int Immunopharmacol 2020; 89:107056. [PMID: 33039955 PMCID: PMC7543893 DOI: 10.1016/j.intimp.2020.107056] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Revised: 09/16/2020] [Accepted: 09/26/2020] [Indexed: 12/18/2022]
Abstract
Patchouli alcohol (PA) is a bioactive component in essential oil extracted from Pogostemon cablin. The present review provides the scientific mechanisms for health beneficial activities of PA in diverse disease models. PA possesses diverse health beneficial activities. Patchouli alcohol (PA), a tricyclic sesquiterpene, is a dominant bioactive component in oil extracted from the aerial parts of Pogostemon cablin (patchouli). Diverse beneficial activities have been reported, including anti-influenza virus, anti-depressant, anti-nociceptive, vasorelaxation, lung protection, brain protection, anti-ulcerogenic, anti-colitis, pre-biotic-like, anti-inflammatory, anti-cancer and protective activities against metabolic diseases. However, detailed mechanistic studies are required to explore the possibility of developing PA as a functional food material or promising drug for the prevention and treatment of human diseases. This review highlights multiple molecular targets and working mechanisms by which PA mediates health benefits.
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Affiliation(s)
- Hee-Seop Lee
- Department of Nutrition and Food Science, College of Agriculture and Natural Resources, University of Maryland, College Park, MD 20742, USA
| | - Jihye Lee
- Department of Nutrition and Food Science, College of Agriculture and Natural Resources, University of Maryland, College Park, MD 20742, USA
| | - Dmitriy Smolensky
- Grain Quality and Structure Research Unit, Agricultural Research Service, U.S. Department of Agriculture, Manhattan, KS 66502, USA
| | - Seong-Ho Lee
- Department of Nutrition and Food Science, College of Agriculture and Natural Resources, University of Maryland, College Park, MD 20742, USA.
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16
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Wu Z, Zeng H, Zhang L, Pu Y, Li S, Yuan Y, Zhang T, Wang B. Patchouli Alcohol: a Natural Sesquiterpene Against Both Inflammation and Intestinal Barrier Damage of Ulcerative Colitis. Inflammation 2020; 43:1423-1435. [PMID: 32388657 DOI: 10.1007/s10753-020-01219-8] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Ulcerative colitis (UC) is a chronic and relapsing inflammatory disorder of the gastrointestinal tract, characterized by diarrhea, hematochezia, abdominal distension, and abdominal pain. The perpetuation of inflammation and the impairment of the intestinal barrier are part of the main courses of UC, responsible for the deteriorating inflammatory condition. Patchouli alcohol (PA), extracted from Pogostemon cablin Benth., is employed to treat both inflammation and intestinal barrier damage. Its curative effect on UC was testified firstly by TNBS-induced UC, a chemically induced colitis, and further tested by DSS-induced UC, an acute attack stage of UC in which the clinical course of human UC occurs frequently. PA reduced the levels of TNF-α, IFN-γ, IL-1β, IL-6, and IL-17 in serum and decreased the mRNA expression of pro-inflammatory cytokines (e.g., iNOS, COX-2, TNF-α, IL-1β, and IL-6). Concurrently, PA upregulated the expression of tight junction protein (e.g., ZO-1, ZO-2, claudin-1, and occludin) and the mRNA of mucin-1 and mucin-2 in both animal models. Further, PA ameliorated both histological damage and clinical parameters. Thus, PA could credibly reduce the expression of pro-inflammatory cytokines, protect the integrity of intestinal epithelial barrier, and repair the macroscopic colon lesions in both colitis models.
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Affiliation(s)
- Zhuona Wu
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Rd, Shanghai, 201203, People's Republic of China
- Experiment Center for Teaching and Learning, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Rd, Shanghai, 201203, People's Republic of China
| | - Hairong Zeng
- Department of Pharmacy, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, 164 Lanxi Rd, Shanghai, 200062, People's Republic of China
| | - Lili Zhang
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Rd, Shanghai, 201203, People's Republic of China
| | - Yiqiong Pu
- Experiment Center for Teaching and Learning, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Rd, Shanghai, 201203, People's Republic of China
| | - Suyun Li
- School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Rd, Shanghai, 201203, People's Republic of China
| | - Yi Yuan
- Department of Pharmacy, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, 164 Lanxi Rd, Shanghai, 200062, People's Republic of China.
| | - Tong Zhang
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Rd, Shanghai, 201203, People's Republic of China.
- Experiment Center for Teaching and Learning, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Rd, Shanghai, 201203, People's Republic of China.
| | - Bing Wang
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Rd, Shanghai, 201203, People's Republic of China.
- State Key Laboratory of Drug Research & Center for Pharmaceutics Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Rd, Shanghai, 201203, People's Republic of China.
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17
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Xie L, Guo YL, Chen YR, Zhang LY, Wang ZC, Zhang T, Wang B. A potential drug combination of omeprazole and patchouli alcohol significantly normalizes oxidative stress and inflammatory responses against gastric ulcer in ethanol-induced rat model. Int Immunopharmacol 2020; 85:106660. [PMID: 32559721 DOI: 10.1016/j.intimp.2020.106660] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2020] [Revised: 05/28/2020] [Accepted: 05/31/2020] [Indexed: 02/06/2023]
Abstract
Omeprazole (OME) is a representative of proton pump inhibitors and widely used in anti-ulcer treatment. However, OME may cause some inevitable side effects and the long-term consequences of OME could increase the risk of diarrhea. Patchouli Alcohol (PA), the main extract of Pogostemonis Herba, have demonstrated benefits in treating gastric ulcer (GU) with low toxicity. The present study aimed to investigate the synergistically protective effects of OME and PA against ethanol-induced GU in rats to study the involvement of antioxidant and anti-inflammatory activities. Moreover, the anti-apoptosis, anti-oxidant and anti-inflammatory effects in H2O2-induced gastric epithelial cells (GES-1) and LPS-induced RAW264.7 cells were determined, as well as the modulation of signaling proteins. The results demonstrated that PA alone or combined with OME provided remarkable benefits by reducing ulcer areas, modulating oxidant stress and inflammatory factors and the therapeutic efficacy was showed to be dose-dependent, which were partly superior to that of high-dose OME only. Additionally, co-treated regimen could superiorly down-regulate cell apoptosis and regulate the levels of oxidant activities and inflammatory cytokines on H2O2-induced GES-1 cells and LPS-induced RAW264.7 cells, which involved with cleaved caspase 3, Bcl-2 and BAX protein expressions and MAPK pathway. We provided a new understanding that the combination of OME and PA possessed gastroprotective effects on modulating cell apoptosis, antioxidant stress and anti-inflammatory responses against GU. Therefore, PA was inferred to take a potential and critic role in gastric mucosa protection.
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Affiliation(s)
- Lu Xie
- Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, 528 Zhang-heng Rd, Shanghai 201203, PR China
| | - Yi-Lin Guo
- Experiment Center for Teaching and Learning, Shanghai University of Traditional Chinese Medicine,1200 Cai-lun Rd, Shanghai 201203, PR China; School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cai-lun Rd, Shanghai 201203, PR China
| | - Yu-Rou Chen
- Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, 528 Zhang-heng Rd, Shanghai 201203, PR China
| | - Li-Ying Zhang
- Foreign Languages Teaching Center, Shanghai University of Traditional Chinese Medicine, 1200 Cai-lun Rd, Shanghai 201203, PR China
| | - Zhi-Cheng Wang
- Department of Laboratory Medicine, Huashan Hospital, Fudan University, 12 Wu-lu-mu-qi Middle Rd, Shanghai 200040, PR China.
| | - Tong Zhang
- Experiment Center for Teaching and Learning, Shanghai University of Traditional Chinese Medicine,1200 Cai-lun Rd, Shanghai 201203, PR China; School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cai-lun Rd, Shanghai 201203, PR China.
| | - Bing Wang
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cai-lun Rd, Shanghai 201203, PR China; State Key Laboratory of Drug Research & Center for Pharmaceutics Research, Shanghai Institute of Materia Medica Chinese Academy of Sciences, 501 Hai-ke Rd, Shanghai 201203, PR China.
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18
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Patchouli alcohol protects against chronic unpredictable mild stress-induced depressant-like behavior through inhibiting excessive autophagy via activation of mTOR signaling pathway. Biomed Pharmacother 2020; 127:110115. [PMID: 32244196 DOI: 10.1016/j.biopha.2020.110115] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2020] [Revised: 03/19/2020] [Accepted: 03/19/2020] [Indexed: 12/28/2022] Open
Abstract
Patchouli alcohol (PA), a tricyclic sesquiterpene, is the major chemical component of patchouli oil. This study investigated the antidepressant-like effect and mechanism of PA in chronic unpredictable mild stress (CUMS). Our results showed that PA markedly attenuated CUMS-induced depressant-like behaviors, including an effective increase of sucrose preference and spontaneous exploratory capacity, as well as reduction of immobility time. In addition, PA markedly attenuated CUMS-induced mTOR, p70S6K, and 4E-BP-1 phosphorylation reduction in the hippocampus. Furthermore, PA reversed CUMS-induced increases in LC3-II and p62 levels and CUMS-induced decrease in PSD-95 and SYN-I levels. These results indicated that the antidepressant-like effect of PA was correlated with the activation of the mTOR signaling pathway. Moreover, behavioral experimental results showed that the antidepressant-like effect of PA was blocked by rapamycin (autophagy inducer and mTOR inhibitor) and chloroquine (autophagic flux inhibitor). These results suggest that PA exerted antidepressant-like effect in CUMS rats through inhibiting autophagy, repairing synapse, and restoring autophagic flux in the hippocampus by activating the mTOR signaling pathway. The results render PA a promising antidepressant agent worthy of further development into a pharmaceutical drug for the treatment of depression.
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19
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Lu Q, Li C, Wu G. Insight into the inhibitory effects of Zanthoxylum nitidum against Helicobacter pylori urease and jack bean urease: Kinetics and mechanism. JOURNAL OF ETHNOPHARMACOLOGY 2020; 249:112419. [PMID: 31759110 DOI: 10.1016/j.jep.2019.112419] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/26/2019] [Revised: 11/18/2019] [Accepted: 11/19/2019] [Indexed: 06/10/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Zanthoxylum nitidum (Roxb.) DC. is a traditional Chinese medicine characterised by anti-inflammatory and anti-Helicobacter pylori, which is widely used to treat H. pylori-induced gastric disease in China. However, the underlying mechanism related to its anti-H. pylori activity remains unclear. Urease plays a crucial role in the colonisation and survival of H. pylori. AIM OF THE STUDY The root aqueous extract of Z. nitidum against H. pylori urease (HPU) and jack bean urease (JBU) was investigated to illuminate the inhibitory potency, kinetics and potential mechanism. MATERIALS AND METHODS Z. nitidum components were determined by UPLC. The enzyme inhibitory effects of Z. nitidum were examined using modified spectrophotometric Berthelot (phenol-hypochlorite) method. Urease inhibition kinetics were determined by Lineweaver-Burk plots. Sulfhydryl group reagents and Ni2+-binding inhibitors were used in the mechanism study. Moreover, the molecular docking technique was used to investigate the binding conformations of the main compounds of Z. nitidum on Urease. RESULTS According to UPLC results, the major components of Z. nitidum were magnoflorine, sanguinarine, nitidine chloride, chelerythrine, skimmianine and L-Sesamin. Z. nitidum has higher enzyme inhibitory activity on HPU (IC50 = 1.29 ± 0.10 mg/mL) than on JBU (IC50 = 2.04 ± 0.27 mg/mL). Enzyme inhibitory kinetic analysis revealed that the type of Z. nitidum inhibition against HPU was a slow-binding and mixed-type, whereas a slow-binding and non-competitive type inhibited JBU. Further mechanism study indicated that the active site of sulfhydryl group might be the target of inhibition by Z. nitidum. The molecular docking study indicated that the above six main components of Z. nitidum exhibited stronger affinity to HPU than to JBU through interacting with the key amino acid residues located on the mobile flap or interacting with the active site Ni2+. Results indicated that these components are potential active ingredients directed against urease. CONCLUSIONS Z. nitidum inactivated urease in a concentration-dependent manner through slow-binding inhibition and binding to the urease active site sulfhydryl group. Our investigation might provide experimental evidence for the traditional application of Z. nitidum in the treatment of H. pylori-associated gastric disorders.
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Affiliation(s)
- Qiang Lu
- Department of Pharmaceutical Sciences, Zunyi Medical University, Zhuhai Campus, Zhuhai, 519041, PR China.
| | - Cailan Li
- Department of Pharmacology, Zunyi Medical University, Zhuhai Campus, Zhuhai, 519041, PR China.
| | - Guosong Wu
- Pharmacy Department, Guangzhou the People's Hospital of Baiyun District, Guangzhou, 510500, PR China.
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20
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Zhang G, Liu M, Song M, Wang J, Cai J, Lin C, Li Y, Jin X, Shen C, Chen Z, Cai D, Gao Y, Zhu C, Lin C, Liu C. Patchouli alcohol activates PXR and suppresses the NF-κB-mediated intestinal inflammatory. JOURNAL OF ETHNOPHARMACOLOGY 2020; 248:112302. [PMID: 31614203 DOI: 10.1016/j.jep.2019.112302] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/23/2019] [Revised: 10/07/2019] [Accepted: 10/11/2019] [Indexed: 06/10/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE The pregnane-X-receptor (PXR) is involved in inflammatory bowel disease (IBD). Patchouli alcohol (PA) has anti-inflammatory effects; however, the effect of PA on IBD pathogenesis remains largely unknown. AIM OF THE STUDY The aim of the present study was to investigate the anti-inflammatory effect of PA, primarily focused on crosstalk between PA-mediated PXR activation and NF-κB inhibition. MATERIALS AND METHODS We evaluated the anti-inflammatory effect of PA with respect to PXR/NF-κB signalling using in vitro and in vivo models. In vitro, PA, identified as a PXR agonist, was evaluated by hPXR transactivation assays and through assessing for CYP3A4 expression and activity. NF-κB inhibition was analysed based on NF-κB luciferase assays, NF-κB-mediated pro-inflammatory gene expression, and NF-κB nuclear translocation after activation of PXR by PA. In vivo, colonic mPXR and NF-κB signalling were analysed to assess PA-mediated the protective effect against dextran sulphate sodium (DSS)-induced colitis. Furthermore, pharmacological inhibition of PXR was further evaluated by examining PA protection against DSS-induced colitis. RESULTS PA induced CYP3A4 expression and activity via an hPXR-dependent mechanism. PA-mediated PXR activation attenuated inflammation by inhibiting NF-κB activity and nuclear translocation. The anti-inflammatory effect of PA on NF-κB was abolished by PXR knockdown. PA prevented DSS-induced inflammation by regulating PXR/NF-κB signalling, whereas pharmacological PXR inhibition abated PA-mediated suppressive effects on NF-κB inflammation signalling. CONCLUSIONS PA activates PXR signalling and suppresses NF-κB signalling, consequently causing amelioration of inflammation. Our results highlight the importance of PXR-NF-κB crosstalk in colitis and suggest a novel therapeutic reagent.
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Affiliation(s)
- Guohui Zhang
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China; Zhuhai Precision Medicine Center, Zhuhai People(')s Hospital, Zhuhai, China
| | - Meijing Liu
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China; Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100191, China
| | - Meng Song
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China
| | - Jueyu Wang
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China
| | - Jiazhong Cai
- Pi-Wei Institute, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China
| | - Chuanquan Lin
- Pi-Wei Institute, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China
| | - Yanwu Li
- Pi-Wei Institute, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China
| | - Xin Jin
- The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China
| | - Chuangpeng Shen
- The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China
| | - Zhao Chen
- The Fifth Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 500095, China
| | - Dake Cai
- The Fifth Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 500095, China
| | - Yong Gao
- Pi-Wei Institute, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.
| | - Chenchen Zhu
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China
| | - Chaozhan Lin
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.
| | - Changhui Liu
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.
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21
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Wu J, Gan Y, Li M, Chen L, Liang J, Zhuo J, Luo H, Xu N, Wu X, Wu Q, Lin Z, Su Z, Liu Y. Patchouli alcohol attenuates 5-fluorouracil-induced intestinal mucositis via TLR2/MyD88/NF-kB pathway and regulation of microbiota. Biomed Pharmacother 2020; 124:109883. [PMID: 32004938 DOI: 10.1016/j.biopha.2020.109883] [Citation(s) in RCA: 51] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2019] [Revised: 01/07/2020] [Accepted: 01/10/2020] [Indexed: 02/09/2023] Open
Abstract
Intestinal mucositis causes great suffering to cancer patients who undergo chemotherapy and radiotherapy. Owing to the uncertain side effects of anticancer drugs to attenuate patients' intestinal mucositis, many studies focused on traditional Chinese medicine (TCM). Patchouli alcohol (PA) is an active compound extracted from Pogostemon cablin, and has potent gastrointestinal protective effect. However, whether PA has an effect on intestinal mucositis is still unknown. Therefore, we established a rat model of intestinal mucositis via intraperitoneal injection of 5-fluorouracil, and intragastrically administrated PA (10, 20, and 40 mg/kg) to evaluate the effect of PA on intestinal mucositis. The routine observation (body weight, food intake, and diarrhea) in rats was used to detect whether PA had an effect on intestinal mucositis. Levels of inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-10, and MPO), mucosal barrier proteins (zonula occludens -1 (ZO-1), claudin-1, occludin, myosin light chain (MLC), and mucin-2) and intestinal microbiota were determined to elucidate the underlying mechanism of PA action on intestinal mucositis in rats. The results showed that PA could effectively improve body weight, food intake, and diarrhea in intestinal mucositis rats, preliminary confirming PA efficacy. Further experiments revealed that PA not only decreased the levels of TNF-α, IL-1β, IL-6, and MPO but also increased the level of IL-10 significantly. In addition, the expression of mucosal barrier proteins and microbiota community were also improved after PA treatment in diseased rats. Hence, PA may prevent the development and progression of intestinal mucositis by improving inflammation, protecting mucosal barrier, and regulating intestinal microbiota.
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Affiliation(s)
- Jiazhen Wu
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China
| | - Yuxuan Gan
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China
| | - Muxia Li
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China
| | - Liping Chen
- Faculty of Health Sciences, University of Macau, Macao, China
| | - Jiali Liang
- Faculty of Science and Engineering, Macquarie University, Balaclava Road, Macquarie Park, NSW, Sydney, 2109, Australia
| | - Jianyi Zhuo
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China
| | - Huijuan Luo
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China
| | - Nan Xu
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China
| | - Xue Wu
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China
| | - Qiduan Wu
- The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China
| | - Zhixiu Lin
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China
| | - Ziren Su
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China; Dongguan & Guangzhou University of Chinese Medicine Cooperative Academy of Mathematical Engineering for Chinese Medicine, Dongguan, 523808, China.
| | - Yuhong Liu
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
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Leong W, Huang G, Khan I, Xia W, Li Y, Liu Y, Li X, Han R, Su Z, Hsiao WLW. Patchouli Essential Oil and Its Derived Compounds Revealed Prebiotic-Like Effects in C57BL/6J Mice. Front Pharmacol 2019; 10:1229. [PMID: 31680986 PMCID: PMC6812344 DOI: 10.3389/fphar.2019.01229] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2019] [Accepted: 09/24/2019] [Indexed: 12/12/2022] Open
Abstract
Pogostemon cablin (Blanco) Benth (PC) is a Chinese medicinal plant traditionally used for the treatment of gastrointestinal symptoms. To investigate the prebiotic effect of patchouli essential oil (PEO) and its derived compounds through the modulation of gut microbiota (GM). C57BL/6J mice were treated with the PEO and three active components of PEO, i.e. patchouli alcohol (PA), pogostone (PO) and β-patchoulene (β-PAE) for 15 consecutive days. Fecal samples and mucosa were collected for GM biomarkers studies. PEO, PA, PO, and β-PAE improve the gut epithelial barrier by altering the status of E-cadherin vs. N-cadherin expressions, and increasing the mucosal p-lysozyme and Muc 2. Moreover, the treatments also facilitate the polarization of M1 to M2 macrophage phenotypes, meanwhile, suppress the pro-inflammatory cytokines. Fecal microbial DNAs were analyzed and evaluated for GM composition by ERIC-PCR and 16S rRNA amplicon sequencing. The GM diversity was increased with the treated groups compared to the control. Further analysis showed that some known short chain fatty acids (SCFAs)-producing bacteria, e.g. Anaerostipes butyraticus, Butytivibrio fibrisolvens, Clostridium jejuense, Eubacterium uniforme, and Lactobacillus lactis were significantly enriched in the treated groups. In addition, the key SCFAs receptors, GPR 41, 43 and 109a, were significantly stimulated in the gut epithelial layer of the treated mice. By contract, the relative abundance of pathogens Sutterlla spp., Fusobacterium mortiferum, and Helicobacter spp. were distinctly reduced by the treatments with PEO and β-PAE. Our findings provide insightful information that the microbiota/host dynamic interaction may play a key role for the pharmacological activities of PEO, PA, PO, and β-PAE.
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Affiliation(s)
- Waikit Leong
- State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China
| | - Guoxin Huang
- State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China
| | - Imran Khan
- State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China
| | - Wenrui Xia
- State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China
| | - Yucui Li
- Guangdong Provincial Key Laboratory of New Chinese Medicinal Development and Research, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yuhong Liu
- Guangdong Provincial Key Laboratory of New Chinese Medicinal Development and Research, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Xiaoang Li
- State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China
| | - Ruixuan Han
- State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China
| | - Ziren Su
- Guangdong Provincial Key Laboratory of New Chinese Medicinal Development and Research, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - W L Wendy Hsiao
- State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China
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Yang L, Zhao L, Zeng T, Chen H, Shao J, Yang S, Tao Z, Yang J, Chen T, Lin X, Chen X, Tang M. Mechanisms Underlying Therapeutic Effects Of Traditional Chinese Medicine On Gastric Cancer. Cancer Manag Res 2019; 11:8407-8418. [PMID: 31571996 PMCID: PMC6754335 DOI: 10.2147/cmar.s218214] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2019] [Accepted: 08/27/2019] [Indexed: 12/13/2022] Open
Abstract
Gastric cancer (GC) is one of the most common malignant tumors in the world. It is the fourth most common cancer and has the second highest mortality rate globally. Metastasis is an important feature of gastric cancer and is the most common cause of death. Exploring the mechanism underlying the metastasis of gastric cancer and searching for new drug targets has become the focus of several studies. Traditional Chinese medicine may show promise for treatment of gastric cancer. In this review, we report the recent progress in research on the anti-metastasis activity of Chinese medicine, to facilitate clinical development of treatments for gastric cancer.
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Affiliation(s)
- Linjun Yang
- Department of Laboratory Animal Centre, Laboratory Animal Centre, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China
| | - Liqian Zhao
- Department of Laboratory Animal Centre, Laboratory Animal Centre, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China
| | - Tianni Zeng
- Department of Laboratory Animal Centre, Laboratory Animal Centre, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China
| | - Hong Chen
- Department of Laboratory Animal Centre, Laboratory Animal Centre, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China
| | - Jingjing Shao
- Department of Laboratory Animal Centre, Laboratory Animal Centre, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China
| | - Song Yang
- Department of Laboratory Animal Centre, Laboratory Animal Centre, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China
| | - Zheying Tao
- Department of Laboratory Animal Centre, Laboratory Animal Centre, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China
| | - Jingqin Yang
- Department of Laboratory Animal Centre, Laboratory Animal Centre, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China
| | - Tongke Chen
- Department of Laboratory Animal Centre, Laboratory Animal Centre, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China
| | - Xiaokun Lin
- Department of Pediatric Surgery, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China
| | - Xiwen Chen
- Department of Laboratory Animal Centre, Laboratory Animal Centre, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China
| | - Mosheng Tang
- Department of Radiotherapy and Chemotherapy, Lishui City People’s Hospital, The Sixth Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang, People’s Republic of China
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Ren WK, Xu YF, Wei WH, Huang P, Lian DW, Fu LJ, Yang XF, Chen FJ, Wang J, Cao HY, Deng YH. Effect of patchouli alcohol on Helicobacter pylori-induced neutrophil recruitment and activation. Int Immunopharmacol 2018; 68:7-16. [PMID: 30599446 DOI: 10.1016/j.intimp.2018.12.044] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2018] [Revised: 12/15/2018] [Accepted: 12/18/2018] [Indexed: 01/12/2023]
Abstract
Neutrophil infiltration typically occurs in Helicobacter pylori (H. pylori)-induced acute gastritis; however, this immune response fails to eradicate H. pylori in vivo. Moreover, reactive oxygen species (ROS), which are generated by neutrophils, cause severe damage to gastric mucosa. Patchouli alcohol (PA) has been reported to have effective anti-oxidative and anti-H. pylori activities, and we investigated its effects on H. pylori-induced neutrophil recruitment and activation in this research. In neutrophil recruitment experiment, H. pylori was injected into rat air pouch to explore the effects of PA (10, 20 and 40 mg/kg) on acute inflammatory response. The results revealed that PA significantly reduced the weight of exudate and the number of neutrophils in the air pouch. Meanwhile, remarkable decrements in TNF-α and IL-8 levels in exudates were observed. In neutrophil activation experiment, rat neutrophils were isolated and activated by using 50 μg/mL H. pylori water-soluble surface protein with or without the treatment of PA (5, 10 or 20 μmol/L). Results indicated that PA not only significantly inhibited the production of ROS, but also reduced the gene and protein expressions of p22/p47-phoxes, and the binding of p22/p47-phoxes. Furthermore, the influence of PA on the neutrophil activation genes of H. pylori (h-nap and sabA) was investigated, and the results showed that expressions of h-nap and sabA were remarkably decreased after PA treatment. In conclusion, PA reduced the recruitment and activation of neutrophils induced by H. pylori, as shown by its inhibition of pro-inflammatory factor generation, p22/p47-phoxes function and H. pylori neutrophil activation-related gene expression.
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Affiliation(s)
- Wen-Kang Ren
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China
| | - Yi-Fei Xu
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China
| | - Wen-Hui Wei
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China
| | - Ping Huang
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China; Dongguan & Guangzhou University of Chinese Medicine Cooperative Academy of Mathematical Engineering for Chinese Medicine, Dongguan 523808, PR China
| | - Da-Wei Lian
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China
| | - Li-Jun Fu
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China
| | - Xu-Feng Yang
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China
| | - Fang-Jun Chen
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China
| | - Jing Wang
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China
| | - Hong-Ying Cao
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China.
| | - Yuan-Hui Deng
- The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR China.
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Lian DW, Xu YF, Ren WK, Fu LJ, Chen FJ, Tang LY, Zhuang HL, Cao HY, Huang P. Unraveling the Novel Protective Effect of Patchouli Alcohol Against Helicobacter pylori-Induced Gastritis: Insights Into the Molecular Mechanism in vitro and in vivo. Front Pharmacol 2018; 9:1347. [PMID: 30524287 PMCID: PMC6262355 DOI: 10.3389/fphar.2018.01347] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2018] [Accepted: 10/31/2018] [Indexed: 12/18/2022] Open
Abstract
Patchouli alcohol (PA), a natural tricyclic sesquiterpene extracted from Pogostemon cablin (Blanco) Benth. (Labiatae), has been found to exhibit anti-Helicobacter pylori and anti-inflammatory properties. In this study, we investigated the protective effect of PA against H. pylori-induced gastritis in vitro and in vivo, and determined the underlying mechanism. In the in vivo experiment, a C57BL/6 mouse model of gastritis was established using H. pylori SS1, and treatments with standard triple therapy or 5, 10, and 20 mg/kg PA were performed for 2 weeks. Results indicated that PA effectively attenuated oxidative stress by decreasing contents of intracellular reactive oxygen species (ROS) and malonyldialdehyde (MDA), and increasing levels of non-protein sulfhydryl (NP-SH), catalase and glutathione (GSH)/glutathione disulphide (GSSG). Additionally, treatment with PA significantly attenuated the secretions of interleukin 1 beta (IL-1β), keratinocyte chemoattractant and interleukin 6 (IL-6). PA (20 mg/kg) significantly protected the gastric mucosa from H. pylori-induced damage. In the in vitro experiment, GES-1 cells were cocultured with H. pylori NCTC11637 at MOI = 100:1 and treated with different doses of PA (5, 10, and 20 μg/ml). Results indicated that PA not only significantly increased the cell viability and decreased cellular lactate dehydrogenase (LDH) leakage, but also markedly elevated the mitochondrial membrane potential and remarkably attenuated GES-1 cellular apoptosis, thereby protecting gastric epithelial cells against injuries caused by H. pylori. PA also inhibited the secretions of pro-inflammatory factors, such as monocyte chemotactic protein 1 (MCP-1), tumor necrosis factor-α (TNF-α) and IL-6. Furthermore, after PA treatment, the combination of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) and cysteine-aspartic proteases 1 (CASPASE-1), the expression levels of NLRP3 inflammasome-related proteins, such as thioredoxin-interacting protein (TXNIP), pro-CASPASE-1, cle-CASPASE-1, and NLRP3 and genes (NLRP3 and CASPASE1) were significantly decreased as compared to the model group. In conclusion, treatment with PA for 2 weeks exhibited highly efficient protective effect against H. pylori-induced gastritis and related damages. The underlying mechanism might involve antioxidant activity, inhibition of pro-inflammatory factor and regulation of NLRP3 inflammasome function. PA exerted anti-H. pylori and anti-gastritis effects and thus had the potential to be a promising candidate for treatment of H. pylori-related diseases.
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Affiliation(s)
- Da-Wei Lian
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yi-Fei Xu
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Wen-Kang Ren
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Li-Jun Fu
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Fang-Jun Chen
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Li-Yao Tang
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Hui-Ling Zhuang
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Hong-Ying Cao
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Ping Huang
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
- Dongguan & Guangzhou University of Chinese Medicine Cooperative Academy of Mathematical Engineering for Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
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Fu Y, Wu HQ, Cui HL, Li YY, Li CZ. Gastroprotective and anti-ulcer effects of oxymatrine against several gastric ulcer models in rats: Possible roles of antioxidant, antiinflammatory, and prosurvival mechanisms. Phytother Res 2018; 32:2047-2058. [PMID: 30024074 DOI: 10.1002/ptr.6148] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2018] [Revised: 06/02/2018] [Accepted: 06/10/2018] [Indexed: 01/16/2023]
Affiliation(s)
- Yan Fu
- Department of Paediatrics; Xinxiang Central Hospital of Henan Province; Xinxiang 453000 China
| | - Huan-qing Wu
- Department of Paediatrics; Xinxiang Central Hospital of Henan Province; Xinxiang 453000 China
| | - Huai-liang Cui
- Department of Paediatrics; Xinxiang Central Hospital of Henan Province; Xinxiang 453000 China
| | - Yue-yun Li
- Department of Paediatrics; Xinxiang Central Hospital of Henan Province; Xinxiang 453000 China
| | - Chang-zheng Li
- Institute of biological life sciences; Xinxiang Medical University; Xinxiang 453003 China
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Shapla UM, Raihan J, Islam A, Alam F, Solayman N, Gan SH, Hossen S, Khalil I. Propolis: The future therapy against Helicobacter pylori-mediated gastrointestinal diseases. J Appl Biomed 2018. [DOI: 10.1016/j.jab.2017.10.007] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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28
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Liang J, Dou Y, Wu X, Li H, Wu J, Huang Q, Luo D, Yi T, Liu Y, Su Z, Chen J. Prophylactic efficacy of patchoulene epoxide against ethanol-induced gastric ulcer in rats: Influence on oxidative stress, inflammation and apoptosis. Chem Biol Interact 2018; 283:30-37. [PMID: 29339218 DOI: 10.1016/j.cbi.2018.01.014] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2017] [Revised: 01/08/2018] [Accepted: 01/11/2018] [Indexed: 12/13/2022]
Abstract
Patchoulene epoxide (PAO), a tricyclic sesquiterpene isolated from the long-stored patchouli oil, has been demonstrated the anti-inflammatory activity in vivo based on our previous study. However, the gastric protective effect of PAO still remains unknown. Therefore, in the present study, ethanol-induced gastric ulcer model was carried out to evaluate the anti-ulcerogenic activity of PAO and to elucidate the potential mechanisms that involves. According to our results, macroscopic examination revealed that PAO could significantly reduce ethanol-induced gastric ulcer areas as compared with the vehicle group, which was also supported by the histological evaluation result. As for its potential mechanism, the anti-inflammatory activity of PAO contributed to gastric protection through reversing the imbalance between pro- and anti-inflammatory cytokines and modulating the expressions of NF-κB pathway-related proteins including p-IκBα, IκBα, p-p65 and p65. Besides, PAO was able to enhance the expressions of antioxidant enzymes including glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT), and down-regulate malonaldehyde (MDA), an indicator of lipid peroxidation. Furthermore, immunohistochemistry analysis exhibited potent anti-apoptosis effect of PAO, as evidence by down-regulating the protein expression of caspase-3, Fas and Fasl. Additionally, we also demonstrated that PAO could replenish PGE2 and NO mucosal defense. In conclusion, these findings suggested that PAO has gastric protective activity against ethanol and this might be related to its influence on inflammatory response, oxidative stress, apoptosis cascade and gastric mucosal defense.
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Affiliation(s)
- Jiali Liang
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
| | - Yaoxing Dou
- The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, China
| | - Xue Wu
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
| | - Huilin Li
- Shenzhen Key Laboratory of Hospital Chinese Medicine Preparation, Guangzhou University of Chinese Medicine, Shenzhen, 518033, China
| | - Jiazhen Wu
- The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, China
| | - Qionghui Huang
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
| | - Dandan Luo
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
| | - Tiegang Yi
- Shenzhen Key Laboratory of Hospital Chinese Medicine Preparation, Guangzhou University of Chinese Medicine, Shenzhen, 518033, China
| | - Yuhong Liu
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
| | - Ziren Su
- Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China; Dongguan Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Dongguan 523808, China.
| | - Jianping Chen
- Shenzhen Key Laboratory of Hospital Chinese Medicine Preparation, Guangzhou University of Chinese Medicine, Shenzhen, 518033, China.
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Manuka honey ( Leptospermum scoparium ) inhibits jack bean urease activity due to methylglyoxal and dihydroxyacetone. Food Chem 2017; 230:540-546. [DOI: 10.1016/j.foodchem.2017.03.075] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2016] [Revised: 02/22/2017] [Accepted: 03/13/2017] [Indexed: 11/20/2022]
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Anti-nociceptive effect of patchouli alcohol: Involving attenuation of cyclooxygenase 2 and modulation of mu-opioid receptor. Chin J Integr Med 2017; 25:454-461. [PMID: 28795389 DOI: 10.1007/s11655-017-2952-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2016] [Indexed: 12/31/2022]
Abstract
OBJECTIVE To explore the anti-nociceptive effect of patchouli alcohol (PA), the essential oil isolated from Pogostemon cablin (Blanco) Bent, and determine the mechanism in molecular levels. METHODS The acetic acid-induced writhing test and formalin-induced plantar injection test in mice were employed to confirm the effect in vivo. Intracellular calcium ion was imaged to verify PA on mu-opioid receptor (MOR). Cyclooxygenase 2 (COX2) and MOR of mouse brain were expressed for determination of PA's target. Cellular experiments were carried out to find out COX2 and MOR expression induced by PA. RESULTS PA significantly reduced latency period of visceral pain and writhing induced by acetic acid saline solution (P<0.01) and allodynia after intra-plantar formalin (P<0.01) in mice. PA also up-regulated COX2 mRNA and protein (P<0.05) with a down-regulation of MOR (P<0.05) both in in vivo and in vitro experiments, which devote to the analgesic effect of PA. A decrease in the intracellular calcium level (P<0.05) induced by PA may play an important role in its anti-nociceptive effect. PA showed the characters of enhancing the MOR expression and reducing the intracellular calcium ion similar to opioid effect. CONCLUSIONS Both COX2 and MOR are involved in the mechanism of PA's anti-nociceptive effect, and the up-regulation of the receptor expression and the inhibition of intracellular calcium are a new perspective to PA's effect on MOR.
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Chang Y, Wei W, Tong L, Liu Y, Zhou A, Chen J, Wei R, Zhang P, Su X. Weikangning therapy in functional dyspepsia and the protective role of Nrf2. Exp Ther Med 2017; 14:2885-2894. [PMID: 28928800 PMCID: PMC5590041 DOI: 10.3892/etm.2017.4892] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2016] [Accepted: 05/16/2017] [Indexed: 12/20/2022] Open
Abstract
Functional dyspepsia (FD) is a non-organic gastrointestinal disorder that has a marked negative impact on quality of life. Compared with conventional pharmacological therapies, the traditional Chinese medicine weikangning (WKN) is a safe and effective treatment for FD. The present study aimed to determine the molecular mechanisms underlying the efficacy of WKN. The effect of different concentrations of WKN on the proliferation of the human gastric mucosal epithelial cell line GES-1 was assessed. The optimal WKN concentration to promote cell proliferation was determined, and this concentration was used to examine the effect of WKN compared with a domperidone-treated positive control group on the antioxidant capacity of GES-1 cells. The effect of WKN treatment on the growth and antioxidant activity of GES-1 cells was also assessed following nuclear factor erythroid 2 like 2 (Nrf2) knockdown. The optimal WKN dose for promoting cell growth was determined to be 0.025 mg/ml; at this concentration the expression of the antioxidant proteins glutathione S-transferase P and superoxide dismutase 2 (SOD2) were significantly elevated (P<0.0001). Furthermore, the amount of reduced glutathione and activity of SOD2 were significantly increased (P<0.0001 and P<0.01, respectively), and malondialdehyde content was significantly decreased, compared with the controls (P<0.001). With WKN treatment, the transcription of Nrf2 and its downstream genes were significantly upregulated (P<0.01), and the level and nuclear distribution of Nrf2 protein was also markedly increased. Following Nrf2 silencing, the protective antioxidant effects of WKN treatment were impaired and GES-1 cell proliferation decreased. The results of the present study suggest that the efficacy of WKN in protecting gastric mucosal epithelial cells in FD is antioxidant-dependent and mediated by Nrf2 activation.
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Affiliation(s)
- Yujuan Chang
- Department of Postgraduate Studies, Oriental Hospital of Beijing University of Chinese Medicine, Beijing 100029, P.R. China.,Department of Gastroenterology, Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing 100102, P.R. China
| | - Wei Wei
- Department of Gastroenterology, Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing 100102, P.R. China
| | - Li Tong
- Institute of Cellular Biology, College of Life Sciences, Beijing Normal University, Beijing 100875, P.R. China
| | - Yanjun Liu
- Department of Gastroenterology, Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing 100102, P.R. China
| | - Aimin Zhou
- Department of Chemistry, Cleveland State University, Cleveland, OH 44114, USA
| | - Jiande Chen
- Department of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, MD 44115, USA
| | - Ruhan Wei
- Department of Chemistry, Cleveland State University, Cleveland, OH 44114, USA
| | - Ping Zhang
- Department of Pathology, Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing 100102, P.R. China
| | - Xiaolan Su
- Department of Gastroenterology, Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing 100102, P.R. China
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32
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Xu YF, Lian DW, Chen YQ, Cai YF, Zheng YF, Fan PL, Ren WK, Fu LJ, Li YC, Xie JH, Cao HY, Tan B, Su ZR, Huang P. In Vitro and In Vivo Antibacterial Activities of Patchouli Alcohol, a Naturally Occurring Tricyclic Sesquiterpene, against Helicobacter pylori Infection. Antimicrob Agents Chemother 2017; 61:e00122-17. [PMID: 28320722 PMCID: PMC5444145 DOI: 10.1128/aac.00122-17] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2017] [Accepted: 03/10/2017] [Indexed: 12/12/2022] Open
Abstract
This study further evaluated the in vitro and in vivo anti-Helicobacter pylori activities and potential underlying mechanism of patchouli alcohol (PA), a tricyclic sesquiterpene. In the in vitro assay, the capacities of PA to inhibit and kill H. pylori were tested on three standard strains at different pH values and on 12 clinical isolates. The effects of PA on H. pylori adhesion (and its alpA, alpB, and babA genes), motility (and its flaA and flaB genes), ultrastructure, and flagellation were investigated. Moreover, the H. pylori resistance to and postantibiotic effect (PAE) of PA were determined. Furthermore, the in vivo effects of PA on H. pylori eradication and gastritis were examined. Results showed that MICs of PA against three standard strains (pH 5.3 to 9) and 12 clinical isolates were 25 to 75 and 12.5 to 50 μg/ml, respectively. The killing kinetics of PA were time and concentration dependent, and its minimal bactericidal concentrations (MBCs) were 25 to 75 μg/ml. In addition, H. pylori adhesion, motility, ultrastructure, and flagellation were significantly suppressed. PA also remarkably inhibited the expression of adhesion genes (alpA and alpB) and motility genes (flaA and flaB). Furthermore, PA treatment caused a longer PAE and less bacterial resistance than clarithromycin and metronidazole. The in vivo study showed that PA can effectively eradicate H. pylori, inhibit gastritis, and suppress the expression of inflammatory mediators (COX-2, interleukin 1β, tumor necrosis factor alpha, and inducible nitric oxide synthase [iNOS]). In conclusion, PA can efficiently kill H. pylori, interfere with its infection process, and attenuate gastritis with less bacterial resistance, making it a potential candidate for new drug development.
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Affiliation(s)
- Y F Xu
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China
| | - D W Lian
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China
| | - Y Q Chen
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China
| | - Y F Cai
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China
| | - Y F Zheng
- Department of Mammary Disease, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China
| | - P L Fan
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China
| | - W K Ren
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China
| | - L J Fu
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China
| | - Y C Li
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China
| | - J H Xie
- Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China
| | - H Y Cao
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China
| | - B Tan
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China
| | - Z R Su
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China
- Dongguan Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Dongguan, People's Republic of China
| | - P Huang
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China
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33
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Patchouli alcohol ameliorates dextran sodium sulfate-induced experimental colitis and suppresses tryptophan catabolism. Pharmacol Res 2017; 121:70-82. [PMID: 28456683 DOI: 10.1016/j.phrs.2017.04.017] [Citation(s) in RCA: 77] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2017] [Revised: 04/05/2017] [Accepted: 04/13/2017] [Indexed: 02/07/2023]
Abstract
Despite the increased morbidity of ulcerative colitis (UC) in recent years, available treatments remain unsatisfactory. Pogostemon cablin has been widely applied to treat a variety of gastrointestinal disorders in clinic for centuries, in which patchouli alcohol (PA, C15H26O) has been identified as the major active component. This study attempted to determine the bioactivity of PA on dextran sulfate sodium (DSS)-induced mice colitis and clarify the mechanism of action. Acute colitis was induced in mice by 3% DSS for 7 days. The mice were then given PA (10, 20 and 40mg/kg) or sulfasalazine (SASP, 200mg/kg) as positive control via oral administration for 7 days. At the end of study, animals were sacrificed and samples were collected for pathological and other analysis. In addition, a metabolite profiling and a targeted metabolite analysis, based on the Ultra-Performance Liquid Chromatography coupled with mass spectrometry (UPLC-MS) approach, were performed to characterize the metabolic changes in plasma. The results revealed that PA significantly reduced the disease activity index (DAI) and ameliorated the colonic injury of DSS mice. The levels of colonic MPO and cytokines involving TNF-α, IFN-γ, IL-1β, IL-6, IL-4 and IL-10 also declined. Furthermore, PA improved the intestinal epithelial barrier by enhancing the level of colonic expression of the tight junction (TJ) proteins, for instance ZO-1, ZO-2, claudin-1 and occludin, and by elevating the levels of mucin-1 and mucin-2 mRNA. The study also demonstrated that PA inhibited the DSS-induced cell death signaling by modulating the apoptosis related Bax and Bcl-2 proteins and down-regulating the necroptosis related RIP3 and MLKL proteins. By comparison, up-regulation of IDO-1 and TPH-1 protein expression in DSS group was suppressed by PA, which was in line with the declined levels of kynurenine (Kyn) and 5-hydroxytryptophan (5-HTP) in plasma. The therapeutic effect of PA was evidently reduced when Kyn was given to mice. In summary, the study successfully demonstrated that PA ameliorated DSS-induced mice acute colitis by suppressing inflammation, maintaining the integrity of intestinal epithelial barrier, inhibiting cell death signaling, and suppressing tryptophan catabolism. The results provided valuable information and guidance for using PA in treatment of UC.
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34
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Abstract
An asymmetric total synthesis of (−)-patchouli alcohol was realized featuring an enantioselective organocatalytic [4 + 2] approach to the [2.2.2] bicyclic core.
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Affiliation(s)
- Guang-Qiang Xu
- CAS Key Laboratory of Synthetic Chemistry of Natural Substances
- Shanghai Institute of Organic Chemistry
- Shanghai 200032
- China
| | - Guo-Qiang Lin
- CAS Key Laboratory of Synthetic Chemistry of Natural Substances
- Shanghai Institute of Organic Chemistry
- Shanghai 200032
- China
| | - Bing-Feng Sun
- CAS Key Laboratory of Synthetic Chemistry of Natural Substances
- Shanghai Institute of Organic Chemistry
- Shanghai 200032
- China
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