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Zhu Y, Jia Y, Zhang E. Oxidative stress modulation in alcohol-related liver disease: From chinese botanical drugs to exercise-based interventions. Front Pharmacol 2025; 16:1516603. [PMID: 40351443 PMCID: PMC12062749 DOI: 10.3389/fphar.2025.1516603] [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: 10/24/2024] [Accepted: 03/10/2025] [Indexed: 05/14/2025] Open
Abstract
Alcohol-related liver disease (ALD) is a chronic liver injury caused by long-term excessive alcohol consumption, with complex and multifaceted pathological mechanisms. Research indicates that oxidative stress (OS), inflammatory responses, and lipid metabolic disturbances induced by alcohol and its metabolites are primary contributors to hepatocyte injury, positioning OS as a key target in ALD treatment. The main non-pharmacological treatment for ALD is alcohol abstinence, while medical treatment primarily relies on Western pharmacological interventions. However, recent research has increasingly highlighted the potential of Chinese botanical drugs in improving histological features and modulating signaling pathways associated with OS in ALD, underscoring the therapeutic potential of traditional Chinese herb medicine. Despite these promising findings, the precise mechanisms and effects of these extracts remain incompletely understood, and potential side effects must be considered. Therefore, a comprehensive analysis of herbal extracts with therapeutic effects is essential to optimize clinical administration and ensure safe, effective treatment. This review focuses on OS as a central theme, categorizing Chinese botanical drugs into six major groups-flavonoids, polyphenols, terpenoids, alkaloids, saponins, and anthraquinones-all widely used in traditional Chinese herb medicine. The review provides an overview of their botanical characteristics and therapeutic actions in the context of ALD, offering insights into OS regulation and exploring their potential as treatments for ALD. Notably, physical exercise shares overlapping mechanisms with botanical drugs in regulating OS. Combining two strategies could offer a promising integrative treatment for ALD, though further research is needed to confirm their synergistic benefits and optimize clinical applications.
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Affiliation(s)
| | | | - Enming Zhang
- School of Sports Medicine and Physical Therapy, Beijing Sport University, Beijing, China
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Wang S, Wang Y, Shan W, Li G, Yan R, Wang Z, Zhao Y, Yao J, Zhang N. Deacetylation of BAP31 by sirtuin 2 attenuates apoptosis of hepatocytes induced by endoplasmic reticulum stress, in chronic alcoholic liver injury. Br J Pharmacol 2025. [PMID: 39887347 DOI: 10.1111/bph.17432] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Revised: 09/25/2024] [Accepted: 11/23/2024] [Indexed: 02/01/2025] Open
Abstract
BACKGROUND AND PURPOSE Endoplasmic reticulum (ER) stress is a crucial pathogenic mechanism in alcoholic liver disease (ALD). B-cell receptor-associated protein 31 (BAP31) can regulate ER homeostasis and anti-apoptosis, but the function and regulation of BAP31 in ALD are unclear. The purpose of this study is to investigate whether BAP31 deacetylation by sirtuin 2 could attenuate ER stress and apoptosis during ALD and to explore whether carnosol could alleviate ALD through the sirtuin 2/BAP31 pathway. EXPERIMENTAL APPROACH A mouse model of ALD was established by feeding mice with alcoholic liquid chow. In vitro, AML-12 cells were stimulated with alcohol. The therapeutic efficacy of carnosol in protecting mice from ALD pathogenesis was evaluated. KEY RESULTS Treatment with carnosol protected mice against ALD and attenuated hepatocyte ER stress and apoptosis. Carnosol up-regulated sirtuin 2 expression, and sirtuin 2knockdown abolished the protective effect of carnosol during ALD. Moreover, sirtuin 2 knockdown reduced BAP31 expression. Carnosol-mediated BAP31 up-regulation was abolished upon knockdown of sirtuin 2. Mechanistically, sirtuin 2 selectively regulates the deacetylation of BAP31 at K158. CONCLUSION AND IMPLICATIONS Taken together, the present study shows for the first time that carnosol exerts its protective efficacy through facilitating sirtuin 2-mediated deacetylation of BAP31 at K158 to attenuate hepatocyte ER stress and apoptosis during ALD. These results provide new therapeutic targets and approaches for combating chronic ALD.
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Affiliation(s)
- Sai Wang
- Department of Pharmacy, Jinshan Hospital, Fudan University, Shanghai, China
- Department of Pharmacology, Dalian Medical University, Dalian, China
| | - Yufeng Wang
- Department of Pharmacology, Dalian Medical University, Dalian, China
- Department of Pharmacy, The Second Hospital of Dalian Medical University, Dalian, China
| | - Wen Shan
- Department of Pharmacy, The Second Hospital of Dalian Medical University, Dalian, China
| | - Guoyang Li
- Department of Pharmacology, Dalian Medical University, Dalian, China
- Department of Pharmacy, The Second Hospital of Dalian Medical University, Dalian, China
| | - Ran Yan
- Department of Pharmacy, The Second Hospital of Dalian Medical University, Dalian, China
| | - Zhecheng Wang
- Department of Pharmacology, Dalian Medical University, Dalian, China
| | - Yan Zhao
- Department of Pharmacology, Dalian Medical University, Dalian, China
| | - Jihong Yao
- Department of Pharmacology, Dalian Medical University, Dalian, China
| | - Ning Zhang
- Department of Pharmacy, Jinshan Hospital, Fudan University, Shanghai, China
- Department of Pharmacology, Dalian Medical University, Dalian, China
- Department of Pharmacy, The Second Hospital of Dalian Medical University, Dalian, China
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Zhang L, Lu L, Jiang S, Yin Z, Tan G, Ning F, Qin Z, Huang J, Huang M, Jin J. Salvianolic acid extract prevents Tripterygium wilfordii polyglycosides-induced acute liver injury by modulating bile acid metabolism. JOURNAL OF ETHNOPHARMACOLOGY 2024; 327:117939. [PMID: 38382651 DOI: 10.1016/j.jep.2024.117939] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/17/2023] [Revised: 02/16/2024] [Accepted: 02/18/2024] [Indexed: 02/23/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Tripterygium wilfordii polyglycosides (TWP) tablet is the most widely used traditional Chinese medicine preparation for the treatment of rheumatoid arthritis (RA), but the hepatotoxicity often limits its widespread application. In traditional use, Salvia miltiorrhiza has cardioprotective and hepatoprotective effects. Salvianolic acid extract (SA) is a hydrophilic component of Salvia miltiorrhiza and has significant antioxidant and hepatoprotective effects. AIM OF THE STUDY To investigate the protective effects of SA on the TWP-induced acute liver injury in rats and to explore the related mechanisms by integration of metabolomics and transcriptomics. MATERIALS AND METHODS SA and TWP extracts were identified by UPLC-Q/TOF-MS. SA (200 mg/kg) was administered for consecutive 7 days. On day 7, TWP (360 mg/kg) was administered by gavage to induce the acute liver injury in rats. Serum biochemical assay and H&E staining were used to evaluate liver damage. Liver metabolomics and transcriptomics were used to explore the potential mechanisms, and further molecular biological experiments such as qPCR and IHC were utilized to validate the relevant signaling pathways. RESULTS SA can prevent liver injury symptoms caused by TWP, such as elevated liver index, elevated ALT and AST, and pathological changes in liver tissue. Liver metabolomics studies showed that TWP can significantly alter the content of individual bile acid in the liver and SA had the most significant impact on the biosynthetic pathway of bile acids. The transcriptomics results of the liver indicated that the genes changed in the SA + TWP group were mainly involved in sterol metabolism, lipid regulation and bile acid homeostasis pathways. The gene expression of Nr1h4, which encodes farnesoid X receptor (FXR), an important regulator of bile acid homeostasis, was significantly changed. Further studies confirmed that SA can prevent the downregulation of FXR and its downstream signaling induced by TWP, thereby regulating bile acid metabolism, ultimately preventing acute liver injury caused by TWP. CONCLUSION Our results demonstrated that SA could protect the liver from TWP-induced hepatic injury by modulation of the bile acid metabolic pathway. SA may provide a new strategy for the protection against TWP-induced acute liver injury.
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Affiliation(s)
- Lei Zhang
- Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China
| | - Langqing Lu
- Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China
| | - Shiqin Jiang
- Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China
| | - Zhaokun Yin
- Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China
| | - Guoyao Tan
- Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China
| | - Fangqing Ning
- Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China
| | - Zhiyan Qin
- Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China
| | - Junyuan Huang
- Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China
| | - Min Huang
- Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China
| | - Jing Jin
- Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
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Gao Y, Gong Y, Lu J, Hao H, Shi X. Targeting YAP1 to improve the efficacy of immune checkpoint inhibitors in liver cancer: mechanism and strategy. Front Immunol 2024; 15:1377722. [PMID: 38550587 PMCID: PMC10972981 DOI: 10.3389/fimmu.2024.1377722] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2024] [Accepted: 03/04/2024] [Indexed: 04/02/2024] Open
Abstract
Liver cancer is the third leading of tumor death, including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). Immune checkpoint inhibitors (ICIs) are yielding much for sufferers to hope for patients, but only some patients with advanced liver tumor respond. Recent research showed that tumor microenvironment (TME) is critical for the effectiveness of ICIs in advanced liver tumor. Meanwhile, metabolic reprogramming of liver tumor leads to immunosuppression in TME. These suggest that regulating the abnormal metabolism of liver tumor cells and firing up TME to turn "cold tumor" into "hot tumor" are potential strategies to improve the therapeutic effect of ICIs in liver tumor. Previous studies have found that YAP1 is a potential target to improve the efficacy of anti-PD-1 in HCC. Here, we review that YAP1 promotes immunosuppression of TME, mainly due to the overstimulation of cytokines in TME by YAP1. Subsequently, we studied the effects of YAP1 on metabolic reprogramming in liver tumor cells, including glycolysis, gluconeogenesis, lipid metabolism, arachidonic acid metabolism, and amino acid metabolism. Lastly, we summarized the existing drugs targeting YAP1 in the treatment of liver tumor, including some medicines from natural sources, which have the potential to improve the efficacy of ICIs in the treatment of liver tumor. This review contributed to the application of targeted YAP1 for combined therapy with ICIs in liver tumor patients.
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Affiliation(s)
- Yuting Gao
- Laboratory of Integrated Medicine Tumor Immunology, Shanxi University of Chinese Medicine, Taiyuan, China
| | - Yi Gong
- Laboratory of Integrated Medicine Tumor Immunology, Shanxi University of Chinese Medicine, Taiyuan, China
| | - Junlan Lu
- Laboratory of Integrated Medicine Tumor Immunology, Shanxi University of Chinese Medicine, Taiyuan, China
| | - Huiqin Hao
- Chinese Medicine Gene Expression Regulation Laboratory, State Administration of Traditional Chinese Medicine, Shanxi University of Chinese Medicine, Taiyuan, China
- Basic Laboratory of Integrated Traditional Chinese and Western, Shanxi University of Chinese Medicine, Taiyuan, China
| | - Xinli Shi
- Laboratory of Integrated Medicine Tumor Immunology, Shanxi University of Chinese Medicine, Taiyuan, China
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Lu J, Li XQ, Chen PP, Zhang JX, Li L, Wang GH, Liu XQ, Jiang CM, Ma KL. Acetyl-CoA synthetase 2 promotes diabetic renal tubular injury in mice by rewiring fatty acid metabolism through SIRT1/ChREBP pathway. Acta Pharmacol Sin 2024; 45:366-377. [PMID: 37770579 PMCID: PMC10789804 DOI: 10.1038/s41401-023-01160-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Accepted: 08/28/2023] [Indexed: 09/30/2023]
Abstract
Diabetic nephropathy (DN) is characterized by chronic low-grade renal inflammatory responses, which greatly contribute to disease progression. Abnormal glucose metabolism disrupts renal lipid metabolism, leading to lipid accumulation, nephrotoxicity, and subsequent aseptic renal interstitial inflammation. In this study, we investigated the mechanisms underlying the renal inflammation in diabetes, driven by glucose-lipid metabolic rearrangement with a focus on the role of acetyl-CoA synthetase 2 (ACSS2) in lipid accumulation and renal tubular injury. Diabetic models were established in mice by the injection of streptozotocin and in human renal tubular epithelial HK-2 cells cultured under a high glucose (HG, 30 mmol/L) condition. We showed that the expression levels of ACSS2 were significantly increased in renal tubular epithelial cells (RTECs) from the diabetic mice and human diabetic kidney biopsy samples, and ACSS2 was co-localized with the pro-inflammatory cytokine IL-1β in RTECs. Diabetic ACSS2-deficient mice exhibited reduced renal tubular injury and inflammatory responses. Similarly, ACSS2 knockdown or inhibition of ACSS2 by ACSS2i (10 µmol/L) in HK-2 cells significantly ameliorated HG-induced inflammation, mitochondrial stress, and fatty acid synthesis. Molecular docking revealed that ACSS2 interacted with Sirtuin 1 (SIRT1). In HG-treated HK-2 cells, we demonstrated that ACSS2 suppressed SIRT1 expression and activated fatty acid synthesis by modulating SIRT1-carbohydrate responsive element binding protein (ChREBP) activity, leading to mitochondrial oxidative stress and inflammation. We conclude that ACSS2 promotes mitochondrial oxidative stress and renal tubular inflammation in DN by regulating the SIRT1-ChREBP pathway. This highlights the potential therapeutic value of pharmacological inhibition of ACSS2 for alleviating renal inflammation and dysregulation of fatty acid metabolic homeostasis in DN. Metabolic inflammation in the renal region, driven by lipid metabolism disorder, is a key factor in renal injury in diabetic nephropathy (DN). Acetyl-CoA synthetase 2 (ACSS2) is abundantly expressed in renal tubular epithelial cells (RTECs) and highly upregulated in diabetic kidneys. Deleting ACSS2 reduces renal fatty acid accumulation and markers of renal tubular injury in diabetic mice. We demonstrate that ACSS2 deletion inhibits ChREBP-mediated fatty acid lipogenesis, mitochondrial oxidative stress, and inflammatory response in RTECs, which play a major role in the progression of diabetic renal tubular injury in the kidney. These findings support the potential use of ACSS2 inhibitors in treating patients with DN.
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Affiliation(s)
- Jian Lu
- Department of Nephrology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China
| | - Xue-Qi Li
- Institute of Nephrology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China
| | - Pei-Pei Chen
- Institute of Nephrology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China
| | - Jia-Xiu Zhang
- Institute of Nephrology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China
| | - Liang Li
- Institute of Nephrology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China
| | - Gui-Hua Wang
- Institute of Nephrology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China
| | - Xiao-Qi Liu
- Department of Nephrology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China
| | - Chun-Ming Jiang
- Department of Nephrology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China.
| | - Kun-Ling Ma
- Department of Nephrology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China.
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Gao H, Li Z, Liu Y, Zhao YK, Cheng C, Qiu F, Gao Y, Lu YW, Song XH, Wang JB, Ma ZT. A clinical experience-based Chinese herbal formula improves ethanol-induced drunken behavior and hepatic steatohepatitis in mice models. Chin Med 2023; 18:47. [PMID: 37127639 PMCID: PMC10150545 DOI: 10.1186/s13020-023-00753-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Accepted: 04/13/2023] [Indexed: 05/03/2023] Open
Abstract
BACKGROUND Bao-Gan-Xing-Jiu-Wan (BGXJW) is a clinical experience-based Chinese herbal formula. Its efficacy, pharmacological safety, targeted function, process quality, and other aspects have met the evaluation standards and the latest requirements of preparations. It could prevent and alleviate the symptoms of drunkenness and alcoholic liver injury clinically. The present work aims to elucidate whether BGXJW could protect against drunkenness and alcoholic liver disease in mice and explore the associated mechanism. MATERIAL AND METHODS We used acute-on-chronic (NIAAA) mice model to induce alcoholic steatosis, and alcohol binge-drinking model to reappear the drunk condition. BGXJW at indicated doses were administered by oral gavage respectively to analyze its effects on alcoholic liver injury and the associated molecular mechanisms. RESULTS BGXJW had no cardiac, hepatic, renal, or intestinal toxicity in mice. Alcoholic liver injury and steatosis in the NIAAA mode were effectively prevented by BGXJW treatment. BGXJW increased the expression of alcohol metabolizing enzymes ADH, CYP2E1, and ALDH2 to enhance alcohol metabolism, inhibited steatosis through regulating lipid metabolism, counteracted alcohol-induced upregulation of lipid synthesis related proteins SREBP1, FASN, and SCD1, meanwhile it enhanced fatty acids β-oxidation related proteins PPAR-α and CPT1A. Alcohol taken enhanced pro-inflammatory TNF-α, IL-6 and down-regulated the anti-inflammatory IL-10 expression in the liver, which were also reversed by BGXJW administration. Moreover, BGXJW significantly decreased the blood ethanol concentration and alleviated drunkenness in the alcohol binge-drinking mice model. CONCLUSIONS BGXJW could effectively relieve drunkenness and prevent alcoholic liver disease by regulating lipid metabolism, inflammatory response, and alcohol metabolism.
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Affiliation(s)
- Han Gao
- College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, Fujian, China
- School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China
- Department of Hepatology, Fifth Medical Center of Chinese, PLA General Hospital, Beijing, 100039, China
| | - Zhen Li
- School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China
- College of Pharmacy, Henan University of Traditional Chinese Medicine, Henan, 450046, Zhengzhou, China
| | - Yao Liu
- School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China
- Department of Infectious Disease, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, China
| | - Yong-Kang Zhao
- School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Cheng Cheng
- School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China
- Department of Pharmacy, Jincheng General Hospital, Jincheng, 048006, Shanxi, China
| | - Feng Qiu
- School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China
| | - Yuan Gao
- School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China
| | - Ya-Wen Lu
- School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China
| | - Xin-Hua Song
- School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China
| | - Jia-Bo Wang
- College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, Fujian, China.
- School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China.
| | - Zhi-Tao Ma
- School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China.
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Hu Z, Zhang H, Wang Y, Li B, Liu K, Ran J, Li L. Exercise activates Sirt1-mediated Drp1 acetylation and inhibits hepatocyte apoptosis to improve nonalcoholic fatty liver disease. Lipids Health Dis 2023; 22:33. [PMID: 36882837 PMCID: PMC9990292 DOI: 10.1186/s12944-023-01798-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Accepted: 02/24/2023] [Indexed: 03/09/2023] Open
Abstract
PURPOSE Aerobic exercise has shown beneficial effects in the prevention and treatment of non-alcoholic fatty liver disease (NAFLD). Nevertheless, the regulatory mechanism is not turely clear. Therefore, we aim to clarify the possible mechanism by investigating the effects of aerobic exercise on NAFLD and its mitochondrial dysfunction. METHODS NAFLD rat model was established by feeding high fat diet. and used oleic acid (OA) to treat HepG2 cells. Changes in histopathology, lipid accumulation, apoptosis, body weight, and biochemical parameters were assessed. In addition, antioxidants, mitochondrial biogenesis and mitochondrial fusion and division were assessed. RESULTS The obtained in vivo results showed that aerobic exercise significantly improved lipid accumulation and mitochondrial dysfunction induced by HFD, activated the level of Sirtuins1 (Srit1), and weakened the acetylation and activity of dynamic-related protein 1 (Drp1). In vitro results showed that activation of Srit1 inhibited OA-induced apoptosis in HepG2 cells and alleviated OA-induced mitochondrial dysfunction by inhibiting Drp1 acetylation and reducing Drp1 expression. CONCLUSION Aerobic exercise alleviates NAFLD and its mitochondrial dysfunction by activating Srit1 to regulate Drp1 acetylation. Our study clarifies the mechanism of aerobic exercise in alleviating NAFLD and its mitochondrial dysfunction and provides a new method for adjuvant treatment of NAFLD.
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Affiliation(s)
- Zongqiang Hu
- First People's Hospital of Kunming City, The Calmette Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Hongyu Zhang
- First People's Hospital of Kunming City, The Calmette Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Yiting Wang
- First People's Hospital of Kunming City, The Calmette Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Boyi Li
- First People's Hospital of Kunming City, The Calmette Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Kaiyu Liu
- First People's Hospital of Kunming City, The Calmette Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Jianghua Ran
- First People's Hospital of Kunming City, The Calmette Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
| | - Li Li
- First People's Hospital of Kunming City, The Calmette Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
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Wang Y, Zhao R, Wu C, Liang X, He L, Wang L, Wang X. Activation of the sirtuin silent information regulator 1 pathway inhibits pathological myocardial remodeling. Front Pharmacol 2023; 14:1111320. [PMID: 36843938 PMCID: PMC9950519 DOI: 10.3389/fphar.2023.1111320] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Accepted: 01/30/2023] [Indexed: 02/12/2023] Open
Abstract
Myocardial remodeling refers to structural and functional disorders of the heart caused by molecular biological changes in the cardiac myocytes in response to neurological and humoral factors. A variety of heart diseases, such as hypertension, coronary artery disease, arrhythmia, and valvular heart disease, can cause myocardial remodeling and eventually lead to heart failure. Therefore, counteracting myocardial remodeling is essential for the prevention and treatment of heart failure. Sirt1 is a nicotinamide adenine dinucleotide+-dependent deacetylase that plays a wide range of roles in transcriptional regulation, energy metabolism regulation, cell survival, DNA repair, inflammation, and circadian regulation. It positively or negatively regulates myocardial remodeling by participating in oxidative stress, apoptosis, autophagy, inflammation, and other processes. Taking into account the close relationship between myocardial remodeling and heart failure and the involvement of SIRT1 in the development of the former, the role of SIRT1 in the prevention of heart failure via inhibition of myocardial remodeling has received considerable attention. Recently, multiple studies have been conducted to provide a better understanding of how SIRT1 regulates these phenomena. This review presents the progress of research involving SIRT1 pathway involvement in the pathophysiological mechanisms of myocardial remodeling and heart failure.
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Affiliation(s)
- Youheng Wang
- Department of Cardiology, The First Affiliated Hospital of Xinxiang Medical University, Heart Center of Xinxiang Medical University, Xinxiang, China
| | - Rusheng Zhao
- Department of Cardiology, The First Affiliated Hospital of Xinxiang Medical University, Heart Center of Xinxiang Medical University, Xinxiang, China
| | - Chengyan Wu
- Department of Cardiology, The First Affiliated Hospital of Xinxiang Medical University, Heart Center of Xinxiang Medical University, Xinxiang, China
| | - Xuefei Liang
- Department of Cardiology, The First Affiliated Hospital of Xinxiang Medical University, Heart Center of Xinxiang Medical University, Xinxiang, China
| | - Lei He
- Department of Cardiology, The First Affiliated Hospital of Xinxiang Medical University, Heart Center of Xinxiang Medical University, Xinxiang, China,Department of Cardiology, Guangyuan Central Hospital, Guangyuan, China
| | - Libo Wang
- Department of Cardiology, The First Affiliated Hospital of Xinxiang Medical University, Heart Center of Xinxiang Medical University, Xinxiang, China,College of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, China,*Correspondence: Libo Wang, ; Xuehui Wang,
| | - Xuehui Wang
- Department of Cardiology, The First Affiliated Hospital of Xinxiang Medical University, Heart Center of Xinxiang Medical University, Xinxiang, China,*Correspondence: Libo Wang, ; Xuehui Wang,
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9
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Xu Q, Liu X, Mohseni G, Hao X, Ren Y, Xu Y, Gao H, Wang Q, Wang Y. Mechanism research and treatment progress of NAD pathway related molecules in tumor immune microenvironment. Cancer Cell Int 2022; 22:242. [PMID: 35906622 PMCID: PMC9338646 DOI: 10.1186/s12935-022-02664-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Accepted: 07/19/2022] [Indexed: 11/21/2022] Open
Abstract
Nicotinamide adenine dinucleotide (NAD) is the core of cellular energy metabolism. NAMPT, Sirtuins, PARP, CD38, and other molecules in this classic metabolic pathway affect many key cellular functions and are closely related to the occurrence and development of many diseases. In recent years, several studies have found that these molecules can regulate cell energy metabolism, promote the release of related cytokines, induce the expression of neoantigens, change the tumor immune microenvironment (TIME), and then play an anticancer role. Drugs targeting these molecules are under development or approved for clinical use. Although there are some side effects and drug resistance, the discovery of novel drugs, the development of combination therapies, and the application of new technologies provide solutions to these challenges and improve efficacy. This review presents the mechanisms of action of NAD pathway-related molecules in tumor immunity, advances in drug research, combination therapies, and some new technology-related therapies.
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Affiliation(s)
- QinChen Xu
- Department of Clinical Laboratory, The Second Hospital of Shandong University, 247 Beiyuan Street, 250033, Jinan, Shandong, China
| | - Xiaoyan Liu
- Department of Clinical Laboratory, The Second Hospital of Shandong University, 247 Beiyuan Street, 250033, Jinan, Shandong, China
| | - Ghazal Mohseni
- Department of Clinical Laboratory, The Second Hospital of Shandong University, 247 Beiyuan Street, 250033, Jinan, Shandong, China
| | - Xiaodong Hao
- Department of Clinical Laboratory, The Second Hospital of Shandong University, 247 Beiyuan Street, 250033, Jinan, Shandong, China
| | - Yidan Ren
- Department of Clinical Laboratory, The Second Hospital of Shandong University, 247 Beiyuan Street, 250033, Jinan, Shandong, China
| | - Yiwei Xu
- Marine College, Shandong University, 264209, Weihai, China
| | - Huiru Gao
- Department of Clinical Laboratory, The Second Hospital of Shandong University, 247 Beiyuan Street, 250033, Jinan, Shandong, China
| | - Qin Wang
- Department of Anesthesiology, Cheeloo College of Medicine, Qilu Hospital, Shandong University, 107 Wenhua Xi Road, Jinan, 250012, Shandong, China.
| | - Yunshan Wang
- Department of Clinical Laboratory, The Second Hospital of Shandong University, 247 Beiyuan Street, 250033, Jinan, Shandong, China.
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Ferdouse A, Clugston RD. Pathogenesis of Alcohol-Associated Fatty Liver: Lessons From Transgenic Mice. Front Physiol 2022; 13:940974. [PMID: 35864895 PMCID: PMC9294393 DOI: 10.3389/fphys.2022.940974] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Accepted: 06/15/2022] [Indexed: 12/18/2022] Open
Abstract
Alcohol-associated liver disease (ALD) is a major public health issue that significantly contributes to human morbidity and mortality, with no FDA-approved therapeutic intervention available. The health burden of ALD has worsened during the COVID-19 pandemic, which has been associated with a spike in alcohol abuse, and a subsequent increase in hospitalization rates for ALD. A key knowledge gap that underlies the lack of novel therapies for ALD is a need to better understand the pathogenic mechanisms that contribute to ALD initiation, particularly with respect to hepatic lipid accumulation and the development of fatty liver, which is the first step in the ALD spectrum. The goal of this review is to evaluate the existing literature to gain insight into the pathogenesis of alcohol-associated fatty liver, and to synthesize alcohol’s known effects on hepatic lipid metabolism. To achieve this goal, we specifically focus on studies from transgenic mouse models of ALD, allowing for a genetic dissection of alcohol’s effects, and integrate these findings with our current understanding of ALD pathogenesis. Existing studies using transgenic mouse models of ALD have revealed roles for specific genes involved in hepatic lipid metabolic pathways including fatty acid uptake, mitochondrial β-oxidation, de novo lipogenesis, triglyceride metabolism, and lipid droplet formation. In addition to reviewing this literature, we conclude by identifying current gaps in our understanding of how alcohol abuse impairs hepatic lipid metabolism and identify future directions to address these gaps. In summary, transgenic mice provide a powerful tool to understand alcohol’s effect on hepatic lipid metabolism and highlight that alcohol abuse has diverse effects that contribute to the development of alcohol-associated fatty liver disease.
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11
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Liu J, Shi Y, Peng D, Wang L, Yu N, Wang G, Chen W. Salvia miltiorrhiza Bge. (Danshen) in the Treating Non-alcoholic Fatty Liver Disease Based on the Regulator of Metabolic Targets. Front Cardiovasc Med 2022; 9:842980. [PMID: 35528835 PMCID: PMC9072665 DOI: 10.3389/fcvm.2022.842980] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Accepted: 03/28/2022] [Indexed: 12/12/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is rapidly prevalent due to its strong association with increased metabolic syndrome such as cardio- and cerebrovascular disorders and diabetes. Few drugs can meet the growing disease burden of NAFLD. Salvia miltiorrhiza Bge. (Danshen) have been used for over 2,000 years in clinical trials to treat NAFLD and metabolic syndrome disease without clarified defined mechanisms. Metabolic targets restored metabolic homeostasis in patients with NAFLD and improved steatosis by reducing the delivery of metabolic substrates to liver as a promising way. Here we systematic review evidence showing that Danshen against NAFLD through diverse and crossing mechanisms based on metabolic targets. A synopsis of the phytochemistry and pharmacokinetic of Danshen and the mechanisms of metabolic targets regulating the progression of NAFLD is initially provided, followed by the pharmacological activity of Danshen in the management NAFLD. And then, the possible mechanisms of Danshen in the management of NAFLD based on metabolic targets are elucidated. Specifically, the metabolic targets c-Jun N-terminal kinases (JNK), sterol regulatory element-binding protein-1c (SREBP-1c), nuclear translocation carbohydrate response element–binding protein (ChREBP) related with lipid metabolism pathway, and peroxisome proliferator-activated receptors (PPARs), cytochrome P450 (CYP) and the others associated with pleiotropic metabolism will be discussed. Finally, providing a critical assessment of the preclinic and clinic model and the molecular mechanism in NAFLD.
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Affiliation(s)
- Jie Liu
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, China
- Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei, China
- Institute of Traditional Chinese Medicine Resources Protection and Development, Anhui Academy of Chinese Medicine, Hefei, China
- Anhui Province Key Laboratory of Traditional Chinese Medicine Decoction Pieces of New Manufacturing Technology, Hefei, China
| | - Yun Shi
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, China
- Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei, China
- Institute of Traditional Chinese Medicine Resources Protection and Development, Anhui Academy of Chinese Medicine, Hefei, China
| | - Daiyin Peng
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, China
- Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei, China
- Institute of Traditional Chinese Medicine Resources Protection and Development, Anhui Academy of Chinese Medicine, Hefei, China
| | - Lei Wang
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, China
- Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei, China
- Anhui Province Key Laboratory of Traditional Chinese Medicine Decoction Pieces of New Manufacturing Technology, Hefei, China
- *Correspondence: Lei Wang,
| | - Nianjun Yu
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, China
- Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei, China
- Institute of Traditional Chinese Medicine Resources Protection and Development, Anhui Academy of Chinese Medicine, Hefei, China
| | - Guokai Wang
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, China
- Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei, China
- Institute of Traditional Chinese Medicine Resources Protection and Development, Anhui Academy of Chinese Medicine, Hefei, China
| | - Weidong Chen
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, China
- Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei, China
- Institute of Traditional Chinese Medicine Resources Protection and Development, Anhui Academy of Chinese Medicine, Hefei, China
- Anhui Province Key Laboratory of Traditional Chinese Medicine Decoction Pieces of New Manufacturing Technology, Hefei, China
- Weidong Chen,
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12
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Xu Y, Geng L, Zhang Y, Jones JA, Zhang M, Chen Y, Tan R, Koffas MAG, Wang Z, Zhao S. De novo Biosynthesis of Salvianolic Acid B in Saccharomyces cerevisiae Engineered with the Rosmarinic Acid Biosynthetic Pathway. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2022; 70:2290-2302. [PMID: 35157428 DOI: 10.1021/acs.jafc.1c06329] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Salvianolic acid B (SAB), also named lithospermic acid B, belongs to a class of water-soluble phenolic acids, originating from plants such as Salvia miltiorrhiza. SAB exhibits a variety of biological activities and has been clinically used to treat cardio- and cerebrovascular diseases and also has great potential as a health care product and medicine for other disorders. However, its biosynthetic pathway has not been completely elucidated. Here, we report the de novo biosynthesis of SAB in Saccharomyces cerevisiae engineered with the heterologous rosmarinic acid (RA) biosynthetic pathway. The created pathway contains seven genes divided into three modules on separate plasmids, pRS424-FjTAL-Sm4CL2, pRS425-SmTAT-SmHPPR or pRS425-SmTAT-CbHPPR, and pRS426-SmRAS-CbCYP-CbCPR. These three modules were cotransformed into S. cerevisiae, resulting in the recombinant strains YW-44 and YW-45. Incubation of the recombinant strains in a basic medium without supplementing any substrates yielded 34 and 30 μg/L of SAB. The findings in this study indicate that the created heterologous RA pathway cooperates with the native metabolism of S. cerevisiae to enable the de novo biosynthesis of SAB. This provides a novel insight into a biosynthesis mechanism of SAB and also lays the foundation for the production of SAB using microbial cell factories.
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Affiliation(s)
- Yingpeng Xu
- The SATCM Key Laboratory for New Resources & Quality Evaluation of Chinese Medicine, The MOE Key Laboratory for Standardization of Chinese Medicines and Shanghai Key Laboratory of Compound Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Lijun Geng
- The SATCM Key Laboratory for New Resources & Quality Evaluation of Chinese Medicine, The MOE Key Laboratory for Standardization of Chinese Medicines and Shanghai Key Laboratory of Compound Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Yiwen Zhang
- The SATCM Key Laboratory for New Resources & Quality Evaluation of Chinese Medicine, The MOE Key Laboratory for Standardization of Chinese Medicines and Shanghai Key Laboratory of Compound Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - J Andrew Jones
- Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, New York 12180, United States
| | - Meihong Zhang
- The SATCM Key Laboratory for New Resources & Quality Evaluation of Chinese Medicine, The MOE Key Laboratory for Standardization of Chinese Medicines and Shanghai Key Laboratory of Compound Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Yuan Chen
- The SATCM Key Laboratory for New Resources & Quality Evaluation of Chinese Medicine, The MOE Key Laboratory for Standardization of Chinese Medicines and Shanghai Key Laboratory of Compound Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Ronghui Tan
- The SATCM Key Laboratory for New Resources & Quality Evaluation of Chinese Medicine, The MOE Key Laboratory for Standardization of Chinese Medicines and Shanghai Key Laboratory of Compound Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Mattheos A G Koffas
- Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, New York 12180, United States
- Department of Biological Sciences, Rensselaer Polytechnic Institutes, Troy, New York 12180, United States
| | - Zhengtao Wang
- The SATCM Key Laboratory for New Resources & Quality Evaluation of Chinese Medicine, The MOE Key Laboratory for Standardization of Chinese Medicines and Shanghai Key Laboratory of Compound Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Shujuan Zhao
- The SATCM Key Laboratory for New Resources & Quality Evaluation of Chinese Medicine, The MOE Key Laboratory for Standardization of Chinese Medicines and Shanghai Key Laboratory of Compound Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
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13
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Chen M, Xing J, Pan D, Gao P. Effect of Chinese Herbal Medicine Mixture 919 Syrup on Regulation of the Ghrelin Pathway and Intestinal Microbiota in Rats With Non-alcoholic Fatty Liver Disease. Front Microbiol 2022; 12:793854. [PMID: 35003024 PMCID: PMC8740226 DOI: 10.3389/fmicb.2021.793854] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Accepted: 11/25/2021] [Indexed: 01/14/2023] Open
Abstract
As a manifestation of metabolic syndrome in the liver, non-alcoholic fatty liver disease (NAFLD) has become the top cause of liver disease in many countries. Recent studies have shown that intestinal microbiota disorder plays an important role in the occurrence and development of NAFLD and that regulating intestinal microbiota provides a new option for NAFLD treatment. In addition, research indicates that risk of NAFLD increases as body mass index rises, and interventions that reduce body weight and change diet can help to lower the incidence of NAFLD. Studies have found that 919 syrup may effectively treat NAFLD in rats by improving liver function and lipid metabolism and regulating body weight and feed intake, however, its potential toxicity and the specific mechanism by which it controls this disease require further exploration. This study assesses both the toxicity of 919 syrup and its regulatory effect on the appetite-related Ghrelin pathway and intestinal microbiota of rats with NAFLD. Results indicate that 919 syrup has no obvious side-effects on body weight, feed intake, blood glucose level, hepatorenal function, and liver tissue structure of normal rats. Moreover, 919 syrup can reverse abnormal changes to expression of Ghrelin pathway genes related to appetite in both the brain and stomach and repair alterations to the intestinal microbiota in rats with NAFLD. This herbal medicine is a safe and promising therapeutic drug for the treatment of NAFLD.
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Affiliation(s)
- Manman Chen
- Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | - Jingwei Xing
- Department of Traditional Chinese Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Danqing Pan
- Department of Traditional Chinese Medicine, Jinshan Hospital, Fudan University, Shanghai, China
| | - Pengfei Gao
- Department of Traditional Chinese Medicine, Jinshan Hospital, Fudan University, Shanghai, China
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14
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Han X, Ding C, Sang X, Peng M, Yang Q, Ning Y, Lv Q, Shan Q, Hao M, Wang K, Wu X, Zhang H, Cao G. Targeting Sirtuin1 to treat aging-related tissue fibrosis: From prevention to therapy. Pharmacol Ther 2021; 229:107983. [PMID: 34480962 DOI: 10.1016/j.pharmthera.2021.107983] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2021] [Revised: 08/18/2021] [Accepted: 08/18/2021] [Indexed: 12/19/2022]
Abstract
Fibrosis, which is characterized by excessive extracellular matrix (ECM) deposition, is a wound-healing response to organ injury and may promote cancer and failure in various organs, such as the heart, liver, lung, and kidney. Aging associated with oxidative stress and inflammation exacerbates cellular dysfunction, tissue failure, and body function disorders, all of which are closely related to fibrosis. Sirtuin-1 (SIRT1) is a class III histone deacetylase that regulates growth, transcription, aging, and metabolism in various organs. This protein is downregulated in organ injury and fibrosis associated with aging. Its expression and distribution change with age in different organs and play critical roles in tissue oxidative stress and inflammation. This review first described the background on fibrosis and regulatory functions of SIRT1. Second, we summarized the relationships of SIRT1 with other proteins and its protective action during fibrosis in the heart, liver, lung and kidney. Third, the activation of SIRT1 in therapies of tissue fibrosis, especially in liver fibrosis and aging-related tissue injury, was analyzed. In conclusion, SIRT1 targeting may be a new therapeutic strategy in fibrosis.
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Affiliation(s)
- Xin Han
- School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, China
| | - Chuan Ding
- School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, China
| | - XiaNan Sang
- School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, China
| | - MengYun Peng
- School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, China
| | - Qiao Yang
- School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, China
| | - Yan Ning
- School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, China
| | - Qiang Lv
- School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, China
| | - QiYuan Shan
- School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, China
| | - Min Hao
- School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, China
| | - KuiLong Wang
- School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, China
| | - Xin Wu
- School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, China
| | - Hongyan Zhang
- Cancer Hospital of The University of Chinese Academy of Sciences, Hangzhou, China
| | - Gang Cao
- School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, China.
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15
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Elebeedy D, Elkhatib WF, Kandeil A, Ghanem A, Kutkat O, Alnajjar R, Saleh MA, Abd El Maksoud AI, Badawy I, Al-Karmalawy AA. Anti-SARS-CoV-2 activities of tanshinone IIA, carnosic acid, rosmarinic acid, salvianolic acid, baicalein, and glycyrrhetinic acid between computational and in vitro insights. RSC Adv 2021; 11:29267-29286. [PMID: 35492070 PMCID: PMC9040650 DOI: 10.1039/d1ra05268c] [Citation(s) in RCA: 80] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Accepted: 08/18/2021] [Indexed: 02/05/2023] Open
Abstract
Six compounds namely, tanshinone IIA (1), carnosic acid (2), rosmarinic acid (3), salvianolic acid B (4), baicalein (5), and glycyrrhetinic acid (6) were screened for their anti-SARS-CoV-2 activities against both the spike (S) and main protease (Mpro) receptors using molecular docking studies. Molecular docking recommended the superior affinities of both salvianolic acid B (4) and glycyrrhetinic acid (6) as the common results from the previously published computational articles. On the other hand, their actual anti-SARS-CoV-2 activities were tested in vitro using plaque reduction assay to calculate their IC50 values after measuring their CC50 values using MTT assay on Vero E6 cells. Surprisingly, tanshinone IIA (1) was the most promising member with IC50 equals 4.08 ng μl-1. Also, both carnosic acid (2) and rosmarinic acid (3) showed promising IC50 values of 15.37 and 25.47 ng μl-1, respectively. However, salvianolic acid (4) showed a weak anti-SARS-CoV-2 activity with an IC50 value equals 58.29 ng μl-1. Furthermore, molecular dynamics simulations for 100 ns were performed for the most active compound from the computational point of view (salvianolic acid 4), besides, the most active one biologically (tanshinone IIA 1) on both the S and Mpro complexes of them (four different molecular dynamics processes) to confirm the docking results and give more insights regarding the stability of both compounds inside the SARS-CoV-2 mentioned receptors, respectively. Also, to understand the mechanism of action for the tested compounds towards SARS-CoV-2 inhibition it was necessary to examine the mode of action for the most two promising compounds, tanshinone IIA (1) and carnosic acid (2). Both compounds (1 and 2) showed very promising virucidal activity with a most prominent inhibitory effect on viral adsorption rather than its replication. This recommended the predicted activity of the two compounds against the S protein of SARS-CoV-2 rather than its Mpro protein. Our results could be very promising to rearrange the previously mentioned compounds based on their actual inhibitory activities towards SARS-CoV-2 and to search for the reasons behind the great differences between their in silico and in vitro results against SARS-CoV-2. Finally, we recommend further advanced preclinical and clinical studies especially for tanshinone IIA (1) to be rapidly applied in COVID-19 management either alone or in combination with carnosic acid (2), rosmarinic acid (3), and/or salvianolic acid (4).
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Affiliation(s)
- Dalia Elebeedy
- College of Biotechnology, Misr University for Science and Technology (MUST) 6th of October City Egypt
| | - Walid F Elkhatib
- Microbiology and Immunology Department, Faculty of Pharmacy, Ain Shams University, African Union Organization St. Abbassia Cairo 11566 Egypt
- Department of Microbiology & Immunology, Faculty of Pharmacy, Galala University New Galala city, Suez Egypt
| | - Ahmed Kandeil
- Center of Scientific Excellence for Influenza Viruses, National Research Centre Giza 12622 Egypt
| | - Aml Ghanem
- Department of Molecular Biology, Genetic Engineering and Biotechnology Research Institute, University of Sadat City Sadat City Egypt
| | - Omnia Kutkat
- Center of Scientific Excellence for Influenza Viruses, National Research Centre Giza 12622 Egypt
| | - Radwan Alnajjar
- Department of Chemistry, Faculty of Science, University of Benghazi Benghazi Libya
- Department of Chemistry, University of Cape Town Rondebosch 7701 South Africa
| | - Marwa A Saleh
- Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy (Girls), Al-Azhar University Nasr City Cairo Egypt
| | - Ahmed I Abd El Maksoud
- Industrial Biotechnology Department, Genetic Engineering and Biotechnology Research Institute, University of Sadat City Sadat City Egypt
| | - Ingy Badawy
- College of Biotechnology, Misr University for Science and Technology (MUST) 6th of October City Egypt
| | - Ahmed A Al-Karmalawy
- Department of Pharmaceutical Medicinal Chemistry, Faculty of Pharmacy, Horus University-Egypt New Damietta 34518 Egypt
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16
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Khanfar MA. Structure-Based Pharmacophore Screening Coupled with QSAR Analysis Identified Potent Natural-Product-Derived IRAK-4 Inhibitors. Mol Inform 2021; 40:e2100025. [PMID: 34427398 DOI: 10.1002/minf.202100025] [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: 01/24/2021] [Accepted: 08/13/2021] [Indexed: 11/10/2022]
Abstract
Interleukin-1 Receptor-Associated Kinase 4 (IRAK-4) has crucial functions in inflammation, innate immunity, and malignancy. Structure-based pharmacophore modeling integrated with validated QSAR analysis was implemented to discover structurally novel IRAK-4 inhibitors from natural products database. The QSAR model combined molecular descriptors with structure-based pharmacophore capable of explaining bioactivity variation of structurally diverse IRAK-4 inhibitors. Manually built pharmacophore model, validated with receiver operating characteristic curve, and selected using the statistically optimum QSAR equation, was applied as a 3D-search query to mine AnalytiCon Discovery database of natural products. Experimental in vitro testing of highest-ranked hits identified uvaretin, saucerneol, and salvianolic acid B as active IRAK-4 inhibitors with IC50 values in low micromolar range.
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Affiliation(s)
- Mohammad A Khanfar
- College of Pharmacy, Alfaisal University, Al Takhassusi Rd, P.O. Box 50927, Riyadh 1, 1533, Saudi Arabia.,Department of Pharmaceutical Sciences, Faculty of Pharmacy, The University of Jordan, P.O Box 13140, Amman, 11942, Jordan
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17
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Role of Silent Information Regulator 1 (SIRT1) in Regulating Oxidative Stress and Inflammation. Inflammation 2021; 43:1589-1598. [PMID: 32410071 DOI: 10.1007/s10753-020-01242-9] [Citation(s) in RCA: 296] [Impact Index Per Article: 74.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Silent information regulator 1 (SIRT1) is a ubiquitously expressed protein and has an intricate role in the pathology, progression, and treatment of several diseases. SIRT1 is a NAD+-dependent deacetylase and regulates gene expression by histone deacetylation. Deletion of SIRT1 in the liver, pancreas, and brain significantly increases the reactive oxygen species (ROS) and inflammatory response. Literature survey on SIRT1 shows the evidence for its role in preventing oxidative stress and inflammation. Oxidative stress and inflammation are closely related pathophysiological processes and are involved in the pathogenesis of a number of chronic disorders such as fatty liver diseases, diabetes, and neurodegenerative diseases. Both oxidative stress and inflammation alter the expression of several genes such as nuclear factor E2 related factor (Nrf2), nuclear factor E2 related factor 2 (Nef2), nuclear factor kappa B (NF-kB), pancreatic and duodenal homeobox factor 1 (PDX1), interleukin-1 (IL1), forkhead box class O (FOXO), and tumour necrosis factor alpha (TNF-α). By annotating this knowledge, we can conclude that modulating the expression of SIRT1 might prevent the onset of diseases inexorably linked to the liver, pancreas, and brain. Graphical Abstract Role of silent information regulator 1 (SIRT1) in the pancreas, brain, and liver.
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18
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Lv B, An T, Wang T, Bao X, Lian J, Wu Y, Hu Y, Zhu J, Zheng C, Hu X, Gao S, Jiang G. Effects of salvianolic acid B on glycometabolism and lipid metabolism in rodents: Meta-analysis. TRADITIONAL MEDICINE AND MODERN MEDICINE 2021. [DOI: 10.1142/s2575900020300040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/09/2022] Open
Abstract
Danshen (Salvia miltiorrhiza) is a herb which has been widely used in China. Salvianolic acid B (SalB) is an aqueous bioactive component derived from Danshen. Here, we aimed to estimate the effect of SalB on glycometabolism and lipid metabolism in rats and mice. We searched four databases until November 2020. The outcome measures were fasting blood glucose (FBG), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDLc), and low-density lipoprotein cholesterol (LDLc). Twenty-four studies involving 547 animals were included. The meta-analysis showed effects of SalB on decreasing the level of FBG, TC, TG, LDLc, and increasing the level of HDLc compared with the control group. In conclusion, the result showed that SalB may regulate the glycometabolism and lipid metabolism in rats or mice, and may be a potential agent for treating metabolic diseases such as diabetes and hyperlipidemia.
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Affiliation(s)
- Bohan Lv
- Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing, P. R. China
| | - Tian An
- Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing, P. R. China
| | - Tingye Wang
- Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing, P. R. China
| | - Xueli Bao
- The Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, P. R. China
| | - Juan Lian
- Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing, P. R. China
| | - Yanxiang Wu
- Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing, P. R. China
| | - Yuanyuan Hu
- Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing, P. R. China
| | - Jiajian Zhu
- Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing, P. R. China
| | - Chunyan Zheng
- Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing, P. R. China
| | - Xuehong Hu
- Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing, P. R. China
| | - Sihua Gao
- Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing, P. R. China
| | - Guangjian Jiang
- Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing, P. R. China
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19
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Chu J, Yan R, Wang S, Li G, Kang X, Hu Y, Lin M, Shan W, Zhao Y, Wang Z, Sun R, Yao J, Zhang N. Sinapic Acid Reduces Oxidative Stress and Pyroptosis via Inhibition of BRD4 in Alcoholic Liver Disease. Front Pharmacol 2021; 12:668708. [PMID: 34149421 PMCID: PMC8212038 DOI: 10.3389/fphar.2021.668708] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Accepted: 05/25/2021] [Indexed: 12/11/2022] Open
Abstract
Alcoholic liver disease (ALD) is one of the main causes of death in chronic liver disease. Oxidative stress and pyroptosis are important factors leading to ALD. Bromodomain-containing protein 4 (BRD4) is a factor that we have confirmed to regulate ALD. As a phenolic acid compound, sinapic acid (SA) has significant effects in antioxidant, anti-inflammatory and liver protection. In this study, we explored whether SA regulates oxidative stress and pyroptosis through BRD4 to play a protective effect in ALD. Male C57BL/6 mice and AML-12 cells were used for experiments. We found that SA treatment largely abolished the up-regulation of BRD4 and key proteins of the canonical pyroptosis signalling in the liver of mice fed with alcohol, while conversely enhanced the antioxidant response. Consistantly, both SA pretreatment and BRD4 knockdown inhibited oxidative stress, pyroptosis, and liver cell damage in vitro. More importantly, the expression levels of BRD4 and pyroptosis indicators increased significantly in ALD patients. Molecule docking analysis revealed a potent binding of SA with BRD4. In conclusion, this study demonstrates that SA reduces ALD through BRD4, which is a valuable lead compound that prevents the ALD process.
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Affiliation(s)
- Junyi Chu
- Department of Pharmacy, The Second Hospital of Dalian Medical University, Dalian, China.,College of Pharmacy, Dalian Medical University, Dalian, China
| | - Ran Yan
- Department of Pharmacy, The Second Hospital of Dalian Medical University, Dalian, China
| | - Sai Wang
- Department of Pharmacy, The Second Hospital of Dalian Medical University, Dalian, China.,College of Pharmacy, Dalian Medical University, Dalian, China
| | - Guoyang Li
- Department of Pharmacy, The Second Hospital of Dalian Medical University, Dalian, China.,College of Pharmacy, Dalian Medical University, Dalian, China
| | - Xiaohui Kang
- College of Pharmacy, Dalian Medical University, Dalian, China
| | - Yan Hu
- Department of Pharmacy, The Second Hospital of Dalian Medical University, Dalian, China.,College of Pharmacy, Dalian Medical University, Dalian, China
| | - Musen Lin
- Department of Pharmacy, The Second Hospital of Dalian Medical University, Dalian, China.,College of Pharmacy, Dalian Medical University, Dalian, China
| | - Wen Shan
- Department of Pharmacy, The Second Hospital of Dalian Medical University, Dalian, China.,Department of Pharmacy, The Third Hospital of Dalian Medical University, Dalian, China
| | - Yan Zhao
- College of Pharmacy, Dalian Medical University, Dalian, China
| | - Zhecheng Wang
- College of Pharmacy, Dalian Medical University, Dalian, China
| | - Ruimin Sun
- College of Pharmacy, Dalian Medical University, Dalian, China
| | - Jihong Yao
- College of Pharmacy, Dalian Medical University, Dalian, China
| | - Ning Zhang
- Department of Pharmacy, The Second Hospital of Dalian Medical University, Dalian, China
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20
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Salvianolic acid B induces browning in 3T3-L1 white adipocytes via activation of β3-AR and ERK signaling pathways. J Funct Foods 2021. [DOI: 10.1016/j.jff.2021.104475] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
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21
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Yan R, Chu J, Zhou Y, Shan W, Hu Y, Lin M, Zhao Y, Sun R, Wang Z, Lv L, Wang L, Yao J, Zhang N. Ubiquitin-specific protease 22 ameliorates chronic alcohol-associated liver disease by regulating BRD4. Pharmacol Res 2021; 168:105594. [PMID: 33826947 DOI: 10.1016/j.phrs.2021.105594] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Revised: 03/19/2021] [Accepted: 03/31/2021] [Indexed: 11/22/2022]
Abstract
Alcohol-associated liver disease (ALD) is a liver system disease caused by alcohol abuse, and it involves complex processes ranging from steatosis to fibrosis, cirrhosis and hepatocellular carcinoma. Steatosis and inflammation are the main phenomena involved in ALD. Ubiquitin-specific protease 22 (USP22) plays an important role in liver steatosis; however, its functional contribution to ALD remains unclear. USP22-silenced mice were fed a Lieber-DeCarli liquid diet. AML-12 and HEK293T cells were used to detect the interaction between USP22 and BRD4. Here, we report that hepatic USP22 expression was dramatically upregulated in mice with ALD. Inflammation and steatosis were significantly ameliorated following USP22 silencing in vivo, as indicated by decreased IL-6 and IL-1β levels. We further showed that the overexpression of USP22 increased inflammation, while knocking down BRD4 suppressed the inflammatory response in AML-12 cells. Notably, USP22 functioned as a BRD4 deubiquitinase to facilitate BRD4 inflammatory functions. More importantly, the expression levels of USP22 and BRD4 in patients with ALD were significantly increased. In conclusion, USP22 acts a key pathogenic factor in ALD by deubiquitinating BRD4, which facilitates the inflammatory response and aggravates ALD.
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Affiliation(s)
- Ran Yan
- Department of Pharmacy, The Second Hospital of Dalian Medical University, Dalian 116000, China; Department of Pharmacology, Dalian Medical University, Dalian 116044, China
| | - Junyi Chu
- Department of Pharmacy, The Second Hospital of Dalian Medical University, Dalian 116000, China; Department of Pharmacology, Dalian Medical University, Dalian 116044, China
| | - Yuanzhang Zhou
- Department of Pharmacology, Dalian Medical University, Dalian 116044, China
| | - Wen Shan
- Department of Pharmacology, Dalian Medical University, Dalian 116044, China; Department of Pharmacy, The Third Hospital of Dalian Medical University, Dalian 116600, China
| | - Yan Hu
- Department of Pharmacy, The Second Hospital of Dalian Medical University, Dalian 116000, China
| | - Musen Lin
- Department of Pharmacy, The Second Hospital of Dalian Medical University, Dalian 116000, China
| | - Yan Zhao
- Department of Pharmacology, Dalian Medical University, Dalian 116044, China
| | - Ruimin Sun
- Department of Pharmacology, Dalian Medical University, Dalian 116044, China
| | - Zhecheng Wang
- Department of Pharmacology, Dalian Medical University, Dalian 116044, China
| | - Li Lv
- Department of Pathology, The Second Hospital of Dalian Medical University, Dalian 116000, China
| | - Liming Wang
- Department of Hepatopancreatobiliary Surgery, The Second Hospital of Dalian Medical University, Dalian 116000, China
| | - Jihong Yao
- Department of Pharmacology, Dalian Medical University, Dalian 116044, China.
| | - Ning Zhang
- Department of Pharmacy, The Second Hospital of Dalian Medical University, Dalian 116000, China.
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Gong Y, Li D, Li L, Yang J, Ding H, Zhang C, Wen G, Wu C, Fang Z, Hou S, Yang Y. Smad3 C-terminal phosphorylation site mutation attenuates the hepatoprotective effect of salvianolic acid B against hepatocarcinogenesis. Food Chem Toxicol 2021; 147:111912. [DOI: 10.1016/j.fct.2020.111912] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2020] [Revised: 11/28/2020] [Accepted: 12/02/2020] [Indexed: 02/07/2023]
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Li R, Wang L, Wang X, Zhang D, Zhang Y, Li Z, Fang M. Simultaneous Determination of Four Monoamine Neurotransmitters and Seven Effective Components of Zaoren Anshen Prescription in Rat Tissue using UPLC-Ms/Ms. CURR PHARM ANAL 2020. [DOI: 10.2174/1573412915666190709095958] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Background:
Zaoren Anshen Prescription (ZAP) is widely used as a classic Chinese Traditional
Medicine (TCM) prescription for the treatment of palpitations and insomnia in China. Some
studies have identified the main active components for its anti-insomnia effect and observed changes
of some endogenous components that are closely related to its anti-insomnia effect. However, simultaneous
determination of four monoamine neurotransmitters and seven effective components of ZAP and
the investigation of their distribution in tissues by using ultra-performance liquid chromatography
with tandem mass spectrometry (UPLC-MS/MS) have not been reported.
Methods:
An ultra-performance liquid chromatography with tandem mass spectrometry method was
developed and validated for simultaneous quantification of four monoamine neurotransmitters (norepinephrine,
dopamine, 5-hydroxy tryptamine and 5-hydroxyindoleacetic acid) and seven prescription
components (danshensu, protocatechualdehyde, spinosin, 6´´´-feruylspinosin, salviaolic acid B, schisandrin
and deoxyschisandrin) in rats’ tissues. Tissue samples were prepared by protein precipitation
with acetonitrile. Chromatographic separation was carried out on a C18 column with a gradient mobile
phase consisting of acetonitrile and 0.01% formic acid water. An electrospray ionization triple quadrupole
concatenation mass spectrometer was set to switch between positive and negative modes in single
run time. All the components were quantitated by multiple-reaction monitoring scanning.
Results:
: The lower limits of quantitation for all analytical components were 0.78 ng/mL-1.99 ng/mL in
the heart, liver, spleen, lung, kidney and brain. All the calibration curves displayed good linearity (r >
0.99544). The precision was evaluated by intra-day and inter-day assays, and the relative standard
deviation (RSD) values were all within 12.67%. The relative errors of the accuracy were all within ±
19.88%. The recovery ranged from 76.00% to 98.78% and the matrix effects of eleven components
were found to be between 85.10% and 96.40%.
Conclusion:
This method was successfully applied to study the distribution of seven components from
ZAP and the concentration changes of four monoamine neurotransmitters after oral ZAP in six tissues.
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Affiliation(s)
- Rong Li
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi’an 710069, China
| | - Lin Wang
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi’an 710069, China
| | - Xiao Wang
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi’an 710069, China
| | - Dian Zhang
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi’an 710069, China
| | - Yafeng Zhang
- Xi’an Institute for Food and Drug Control, Xi’an 710054, China
| | - Zhuo Li
- Xi’an Institute for Food and Drug Control, Xi’an 710054, China
| | - Minfeng Fang
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi’an 710069, China
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24
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Xiao Z, Liu W, Mu YP, Zhang H, Wang XN, Zhao CQ, Chen JM, Liu P. Pharmacological Effects of Salvianolic Acid B Against Oxidative Damage. Front Pharmacol 2020; 11:572373. [PMID: 33343348 PMCID: PMC7741185 DOI: 10.3389/fphar.2020.572373] [Citation(s) in RCA: 91] [Impact Index Per Article: 18.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Accepted: 09/25/2020] [Indexed: 12/15/2022] Open
Abstract
Salvianolic acid B (Sal B) is one of the main active ingredients of Salvia miltiorrhiza, with strong antioxidant effects. Recent findings have shown that Sal B has anti-inflammatory, anti-apoptotic, anti-fibrotic effects and can promote stem cell proliferation and differentiation, and has a beneficial effect on cardiovascular and cerebrovascular diseases, aging, and liver fibrosis. Reactive oxygen species (ROS) include oxygen free radicals and oxygen-containing non-free radicals. ROS can regulate cell proliferation, survival, death and differentiation to regulate inflammation, and immunity, while Sal B can scavenge oxygen free radicals by providing hydrogen atoms and reduce the production of oxygen free radicals and oxygen-containing non-radicals by regulating the expression of antioxidant enzymes. The many pharmacological effects of Sal B may be closely related to its elimination and inhibition of ROS generation, and Nuclear factor E2-related factor 2/Kelch-like ECH-related protein 1 may be the core link in its regulation of the expression of antioxidant enzyme to exert its antioxidant effect. What is confusing and interesting is that Sal B exhibits the opposite mechanisms in tumors. To clarify the specific target of Sal B and the correlation between its regulation of oxidative stress and energy metabolism homeostasis will help to further understand its role in different pathological conditions, and provide a scientific basis for its further clinical application and new drug development. Although Sal B has broad prospects in clinical application due to its extensive pharmacological effects, the low bioavailability is a serious obstacle to further improving its efficacy in vivo and promoting clinical application. Therefore, how to improve the availability of Sal B in vivo requires the joint efforts of many interdisciplinary subjects.
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Affiliation(s)
- Zhun Xiao
- Institute of Interdisciplinary Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Wei Liu
- Institute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Shanghai Key Laboratory of Traditional Chinese Medicine, Shanghai, China
| | - Yong-ping Mu
- Institute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Shanghai Key Laboratory of Traditional Chinese Medicine, Shanghai, China
| | - Hua Zhang
- Institute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Shanghai Key Laboratory of Traditional Chinese Medicine, Shanghai, China
| | - Xiao-ning Wang
- Institute of Interdisciplinary Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Shanghai Key Laboratory of Traditional Chinese Medicine, Shanghai, China
| | - Chang-qing Zhao
- Institute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Shanghai Key Laboratory of Traditional Chinese Medicine, Shanghai, China
| | - Jia-mei Chen
- Institute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Shanghai Key Laboratory of Traditional Chinese Medicine, Shanghai, China
| | - Ping Liu
- Institute of Interdisciplinary Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Institute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Shanghai Key Laboratory of Traditional Chinese Medicine, Shanghai, China
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25
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An Overview of the Mechanism of Penthorum chinense Pursh on Alcoholic Fatty Liver. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2020; 2020:4875764. [PMID: 33014105 PMCID: PMC7519454 DOI: 10.1155/2020/4875764] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/12/2020] [Revised: 08/13/2020] [Accepted: 08/28/2020] [Indexed: 12/11/2022]
Abstract
Alcohol liver disease (ALD) caused by excessive alcohol consumption is a progressive disease, and alcohol fatty liver disease is the primary stage. Currently, there is no approved drug for its treatment. Abstinence is the best way to heal, but patients' compliance is poor. Unlike other chronic diseases, alcohol fatty liver disease is not caused by nutritional deficiencies; it is caused by the molecular action of ingested alcohol and its metabolites. More and more studies have shown the potential of Penthorum chinense Pursh (PCP) in the clinical use of alcohol fatty liver treatment. The purpose of this paper is to reveal from the essence of PCP treatment of alcohol liver mechanism mainly by the ethanol dehydrogenase (ADH) and microsomal ethanol oxidation system-dependent cytochrome P4502E1 (CYP2E1) to exert antilipogenesis, antioxidant, anti-inflammatory, antiapoptotic, and autophagy effects, with special emphasis on its mechanisms related to SIRT1/AMPK, KEAP-1/Nrf2, and TLR4/NF-κB. Overall, data from the literature shows that PCP appears to be a promising hepatoprotective traditional Chinese medicine (TCM).
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26
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Pang Y, Zhang PC, Lu RR, Li HL, Li JC, Fu HX, Cao YW, Fang GX, Liu BH, Wu JB, Zhou JY, Zhou Y. Andrade-Oliveira Salvianolic Acid B Modulates Caspase-1-Mediated Pyroptosis in Renal Ischemia-Reperfusion Injury via Nrf2 Pathway. Front Pharmacol 2020; 11:541426. [PMID: 33013384 PMCID: PMC7495093 DOI: 10.3389/fphar.2020.541426] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Accepted: 08/17/2020] [Indexed: 12/19/2022] Open
Abstract
Acute kidney injury (AKI) is a serious disease characterized by a rapid decline in kidney function. Oxidative stress is the primary pathogenesis of AKI. Salvianolic acid B (SalB), a water-soluble compound extracted from Salvia miltiorrhiza, possesses a potent antioxidant activity. Here, we investigated the protective effect of SalB against renal ischemia-reperfusion injury (I/R) in mice. Briefly, by analyzing renal function, oxidative stress markers and inflammatory biomarkers, we found that SalB could improve kidney damage, reduce oxidative stress and inflammatory factor levels. Interestingly, the expression of the NLR family pyrin domain-containing 3 (NLRP3), caspase-1, pyroptosis related proteins gasdermin D (GSDMD) and interleukin (IL)-1β, which were significantly upregulated in the kidney tissues of I/R group, was effectively reversed by SalB. Meanwhile, renal tubular epithelial cells hypoxia and reoxygenation model was used to explore pyroptosis of caspase-1-dependent. Further mechanism study showed that the SalB pretreatment could promote the increase of nuclear factor erythroid-2 related factor 2 (Nrf2) nuclear accumulation, which significantly suppressed oxidative stress, proinflammatory cytokines, NLRP3 inflammasome activation and pyroptosis. These results indicate that SalB can inhibit caspase-1/GSDMD-mediated pyroptosis by activating Nrf2/NLRP3 signaling pathway, resulting in alleviating I/R injury in mice.
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Affiliation(s)
- Yu Pang
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Pei-Chun Zhang
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Rui-Rui Lu
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Hong-Lian Li
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Ji-Cheng Li
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Hong-Xin Fu
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yi-Wen Cao
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Guo-Xing Fang
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Bi-Hao Liu
- Department of Urology, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.,Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Jun-Biao Wu
- Department of Clinical Pharmacy, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Jiu-Yao Zhou
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yuan Zhou
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
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27
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Lan Y, Yan R, Shan W, Chu J, Sun R, Wang R, Zhao Y, Wang Z, Zhang N, Yao J. Salvianic acid A alleviates chronic alcoholic liver disease by inhibiting HMGB1 translocation via down-regulating BRD4. J Cell Mol Med 2020; 24:8518-8531. [PMID: 32596881 PMCID: PMC7412690 DOI: 10.1111/jcmm.15473] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2020] [Revised: 05/05/2020] [Accepted: 05/13/2020] [Indexed: 12/11/2022] Open
Abstract
Alcoholic liver disease (ALD) is the major cause of chronic liver disease and a global health concern. ALD pathogenesis is initiated with liver steatosis, and ALD can progress to steatohepatitis, fibrosis, cirrhosis and even hepatocellular carcinoma. Salvianic acid A (SAA) is a phenolic acid component of Danshen, a Chinese herbal medicine with possible hepatoprotective properties. The purpose of this study was to investigate the effect of SAA on chronic alcoholic liver injury and its molecular mechanism. We found that SAA significantly inhibited alcohol‐induced liver injury and ameliorated ethanol‐induced hepatic inflammation. These protective effects of SAA were likely carried out through its suppression of the BRD4/HMGB1 signalling pathway, because SAA treatment largely diminished alcohol‐induced BRD4 expression and HMGB1 nuclear translocation and release. Importantly, BRD4 knockdown prevented ethanol‐induced HMGB1 release and inflammatory cytokine production in AML‐12 cells. Similarly, alcohol‐induced pro‐inflammatory cytokines were blocked by HMGB1 siRNA. Collectively, our results reveal that activation of the BRD4/HMGB1 pathway is involved in ALD pathogenesis. Therefore, manipulation of the BRD4/HMGB1 pathway through strategies such as SAA treatment holds great therapeutic potential for chronic alcoholic liver disease therapy.
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Affiliation(s)
- Yanwen Lan
- Department of Pharmacy, The Second Hospital of Dalian Medical University, Dalian, China.,Department of Pharmacology, Dalian Medical University, Dalian, China.,Department of Pharmacy, Dalian Seventh People's Hospital, Dalian, China
| | - Ran Yan
- Department of Pharmacy, The Second Hospital of Dalian Medical University, Dalian, China.,Department of Pharmacology, Dalian Medical University, Dalian, China
| | - Wen Shan
- Department of Pharmacy, The Second Hospital of Dalian Medical University, Dalian, China.,Department of Pharmacy, The Third Hospital of Dalian Medical University, Dalian, China
| | - Junyi Chu
- Department of Pharmacy, The Second Hospital of Dalian Medical University, Dalian, China.,Department of Pharmacology, Dalian Medical University, Dalian, China
| | - Ruimin Sun
- Department of Pharmacology, Dalian Medical University, Dalian, China
| | - Ruiwen Wang
- Department of Pharmacology, Dalian Medical University, Dalian, China
| | - Yan Zhao
- Department of Pharmacology, Dalian Medical University, Dalian, China
| | - Zhanyu Wang
- Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Ning Zhang
- Department of Pharmacy, The Second Hospital of Dalian Medical University, Dalian, China
| | - Jihong Yao
- Department of Pharmacology, Dalian Medical University, Dalian, China
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28
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Total Salvianolic Acid Injection Prevents Ischemia/Reperfusion-Induced Myocardial Injury Via Antioxidant Mechanism Involving Mitochondrial Respiratory Chain Through the Upregulation of Sirtuin1 and Sirtuin3. Shock 2020; 51:745-756. [PMID: 29863652 PMCID: PMC6511432 DOI: 10.1097/shk.0000000000001185] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Supplemental Digital Content is available in the text Sirtuin1 (Sirt1) and Sirtuin3 (Sirt3) are known to participate in regulating mitochondrial function. However, whether Total Salvianolic Acid Injection (TSI) protects against myocardial ischemia/reperfusion (I/R) injury through regulating Sirt1, Sirt3, and mitochondrial respiratory chain complexes is unclear. The aim of this study was to explore the effects of TSI on I/R-induced myocardial injury and the underlying mechanism. Male Sprague–Dawley rats were subjected to 30 min occlusion of the left anterior descending coronary artery followed by 90 min reperfusion with or without TSI treatment (8 mg/kg/h). The results demonstrated that TSI attenuated I/R-induced myocardial injury by the reduced infarct size, recovery of myocardial blood flow, and decreased cardiac apoptosis. Moreover, TSI protected heart from oxidative insults, such as elevation of myeloperoxidase, malondialdehyde, hydrogen peroxide, ROS, as well as attenuated I/R-elicited downregulation of Sirt1, Sirt3, NADH dehydrogenase [ubiquinone] 1 alpha subcomplex 10 (NDUFA10), succinate dehydrogenase complex, subunit A, flavoprotein variant (SDHA), and restoring mitochondrial respiratory chain complexes activity. The in vitro study in H9c2 cells using siRNA transfection further confirmed the critical role of Sirt1 and Sirt3 in the effect of TSI on the expression of NDUFA10 and SDHA. These results demonstrated that TSI attenuated I/R-induced myocardial injury via inhibition of oxidative stress, which was related to the activation of NDUFA10 and SDHA through the upregulation of Sirt1 and Sirt3.
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Chen M, Xing J, Pan D, Peng X, Gao P. Chinese herbal medicine mixture 919 syrup alleviates nonalcoholic fatty liver disease in rats by inhibiting the NF-κB pathway. Biomed Pharmacother 2020; 128:110286. [PMID: 32521450 DOI: 10.1016/j.biopha.2020.110286] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2020] [Revised: 05/14/2020] [Accepted: 05/16/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND In many countries, nonalcoholic fatty liver disease (NAFLD) has risen to be the leading cause of liver disease, seriously threatening public health, while effective medical treatments are currently limited. 919 syrup (919 T J) is a Chinese herbal medicine, and both clinical and experimental studies have revealed that it can improve liver function. OBJECTIVE To study whether 919 T J shows a protective effect in a NAFLD rat model and explore its underlying mechanism, with a focus on the NF-κB pathway. METHODS Rats were randomly divided into three groups, including a control group, NAFLD group, and 919 T J group (n = 10 each). The control group received a standard diet, and the other two groups were fed a high-fat diet to establish the NAFLD model. From week 10, rats in the 919 T J group were intragastrically administered 919 T J for 4 weeks, and the NAFLD group was administered the same amount of saline. All rats were anesthetized at the beginning of week 14 to collect blood and liver specimens. Serum lipid levels, serum biochemical markers of liver function, and the gene expression levels of IL-1β, TNF-α, CXCL6, CXCR1, SREBP-1c, PPARγ, and NF-κB in the liver were measured. Oil Red O and hematoxylin and eosin staining of the liver was performed to observe pathological changes in the liver. RESULTS Significant abnormalities in serum lipid levels and serum biochemical markers of liver function were found in the NAFLD group relative to those in the control group. In addition, serious abnormalities were noted in the expression levels of liver inflammatory factors and lipid metabolism-related genes. Treatment of NAFLD rats with 919 T J reduced body weight and food intake and ameliorated the abnormal blood lipid levels and liver function markers. By regulating the NF-κB pathway, 919 T J downregulated the NF-κB-related proinflammatory signals, ameliorating the expression of inflammatory (IL-1β, TNF-α, CXCL6, and CXCR1) and lipid metabolism-related (SREBP-1c) factors in the liver and improving the NAFLD-induced pathological changes in the liver. CONCLUSION 919 T J reduces the liver injury, steatosis, and inflammation caused by NAFLD, thus reversing the disease process.
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Affiliation(s)
- Manman Chen
- Department of TCM, Jinshan Hospital, Fudan University, Shanghai, China
| | - Jingwei Xing
- Department of TCM, Jinshan Hospital, Fudan University, Shanghai, China
| | - Danqing Pan
- Department of TCM, Jinshan Hospital, Fudan University, Shanghai, China
| | - Xiuhua Peng
- Department of Animal Experiments, Shanghai Public Health Clinical Center, Shanghai, China
| | - Pengfei Gao
- Department of TCM, Jinshan Hospital, Fudan University, Shanghai, China.
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Sinha S, Sharma S, Vora J, Shrivastava N. Emerging role of sirtuins in breast cancer metastasis and multidrug resistance: Implication for novel therapeutic strategies targeting sirtuins. Pharmacol Res 2020; 158:104880. [PMID: 32442721 DOI: 10.1016/j.phrs.2020.104880] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2020] [Revised: 04/25/2020] [Accepted: 04/27/2020] [Indexed: 12/13/2022]
Abstract
Sirtuins (SIRTs), a class III histone deacetylases (HDACs) that require NAD+ as a cofactor and include SIRT1-7 proteins in mammals. Accumulative evidence has established that every sirtuin possesses exclusive and poised biology, implicating their role in the regulation of multifaceted biological functions leading to breast cancer initiation, progression, and metastasis. This article provides an outline of recent developments in the role of sirtuins in breast cancer metastasis and development of multidrug resistance (MDR). In addition, we have also highlighted the impending prospects of targeting SIRTs to overcome MDR to bring advancement in breast cancer management. Further, this review will focus on strategies for improving the activity and efficacy of existing cancer therapeutics by combining (adjuvant treatment/therapy) them with sirtuin inhibitors/modulators. All available as well as newly discovered synthetic and dietary sirtuin inhibitors, activators/modulators have been extensively reviewed and compiled to provide a rationale for targeting sirtuins. Further, we discuss their potential in developing future therapeutics against sirtuins proposing their use along with conventional chemotherapeutics to overcome the problem of breast cancer metastasis and MDR.
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Affiliation(s)
- Sonam Sinha
- Department of Pharmacognosy and Phytochemistry, B. V. Patel Pharmaceutical Education and Research Development (PERD) Centre, Ahmedabad, 380054, Gujarat, India; School of Science, Gujarat University, Ahmedabad, Gujarat, India
| | - Sonal Sharma
- Department of Pharmacognosy and Phytochemistry, B. V. Patel Pharmaceutical Education and Research Development (PERD) Centre, Ahmedabad, 380054, Gujarat, India
| | - Jaykant Vora
- Department of Pharmacognosy and Phytochemistry, B. V. Patel Pharmaceutical Education and Research Development (PERD) Centre, Ahmedabad, 380054, Gujarat, India; School of Science, Gujarat University, Ahmedabad, Gujarat, India
| | - Neeta Shrivastava
- Department of Pharmacognosy and Phytochemistry, B. V. Patel Pharmaceutical Education and Research Development (PERD) Centre, Ahmedabad, 380054, Gujarat, India.
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Jin S, Yang L, Fan X, Wu M, Xu Y, Chen X, Lin Z, Geng Z. Effect of divergence in residual feed intake on expression of lipid metabolism-related genes in the liver of meat-type ducks1. J Anim Sci 2019; 97:3947-3957. [PMID: 31325379 DOI: 10.1093/jas/skz241] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2019] [Accepted: 07/17/2019] [Indexed: 12/13/2022] Open
Abstract
Lipid metabolism is considered one of the important factors affecting residual feed intake (RFI). However, the relationship between RFI and expression of lipid metabolism-related genes is unknown in meat-type ducks. To address this issue, a total of 1,000 male meat-type ducks with similar body weight were randomly selected to measure body weight gain and feed intake from 21 to 42 d of age to estimate RFI. The 8 greatest- (high RFI [HRFI]) and lowest- (low RFI [LRFI]) ranking birds were then selected for the present study. Relative expressions of key genes, namely sirtuin 1 (Sirt1), forkhead box O1 (Foxo1), peroxisome proliferator-activated receptor gamma (PPARγ), sterol regulatory element-binding transcription factor 1c (SREBP-1c), fas cell surface death receptor (FAS), acetyl-CoA carboxylase alpha (ACC), carnitine palmitoyltransferase 1A (CPT1A), and acyl-CoA oxidase 1 (ACOX1), were then determined in the HRFI and LRFI ducks by quantitative PCR. The results showed that RFI, feed conversion ratio (FCR), and average daily feed intake (ADFI) were significantly lower (P < 0.05) in LRFI ducks than in HRFI ducks. In addition, expression of Sirt1, Foxo1, CPT1A, and ACOX1 were significantly higher in LRFI ducks than in HRFI ducks (P < 0.05), whereas PPARγ and FAS expression levels were significantly lower in LRFI ducks than in HRFI ducks (P < 0.01). Correlation analysis showed that Sirt1, CPT1A, and ACOX1 expressions were significantly negatively correlated with FCR (r = -0.81 to -0.93; P < 0.01), whereas PPARγ and FAS expressions were significantly positively correlated with FCR (r = 0.74 to 0.87; P < 0.01). PPARγ expression was significantly positively correlated with RFI (r = 0.83; P < 0.01), whereas CPT1A and ACOX1 expressions were significantly negatively correlated with RFI (r = -0.84 to -0.89; P < 0.01). Sirt1 mRNA expression was positively correlated with Foxo1, CPT1A, and ACOX1 mRNA expression (r = 0.78 to 0.92; P < 0.01). Association of Foxo1 with CPT1A and ACOX1 was positive (r = 0.88 to 0.96; P < 0.01). These results suggest that genes related to fatty acid oxidation are upregulated in the liver of ducks with high feed efficiency, while genes associated with lipid synthesis are downregulated. Furthermore, the inclusion of lipid metabolism-related genes in future breeding programs might be beneficial for selecting ducks with greater feed efficiency phenotype.
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Affiliation(s)
- Sihua Jin
- College of Animal Science and Technology, Anhui Agricultural University, Hefei, China
| | - Lei Yang
- College of Animal Science and Technology, Anhui Agricultural University, Hefei, China
| | - Xinfeng Fan
- College of Animal Science and Technology, Anhui Agricultural University, Hefei, China
| | - Minghui Wu
- College of Animal Science and Technology, Anhui Agricultural University, Hefei, China
| | - Yuan Xu
- College of Animal Science and Technology, Anhui Agricultural University, Hefei, China
| | - Xianzen Chen
- Anhui Provincial Key Laboratory of Local Animal Genetic Resources Conservation and Biobreeding, Hefei, China
| | - Zhiqiang Lin
- Huangshan Qiangying Duck Breeding Co. Ltd., Huangshan, China
| | - Zhaoyu Geng
- College of Animal Science and Technology, Anhui Agricultural University, Hefei, China
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Zhang J, Bi R, Meng Q, Wang C, Huo X, Liu Z, Wang C, Sun P, Sun H, Ma X, Wu J, Liu K. Catalpol alleviates adriamycin-induced nephropathy by activating the SIRT1 signalling pathway in vivo and in vitro. Br J Pharmacol 2019; 176:4558-4573. [PMID: 31378931 DOI: 10.1111/bph.14822] [Citation(s) in RCA: 66] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2018] [Revised: 06/28/2019] [Accepted: 07/26/2019] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND AND PURPOSE Catalpol, a water-soluble active ingredient isolated from Rehmannia glutinosa, exhibits multiple pharmacological activities. However, the mechanism(s) underlying protection against renal injury by catalpol remains unknown. EXPERIMENTAL APPROACH Adriamycin-induced kidney injury models associated with podocyte damage were employed to investigate the nephroprotective effects of catalpol. In vivo, TUNEL and haematoxylin-eosin staining was used to evaluate the effect of catalpol on kidney injury in mice. In vitro, effects of catalpol on podocyte damage induced by adriamycin was determined by elisa kit, flow cytometry, Hoechst 33342, and TUNEL staining. The mechanism was investigated by siRNA, EX527, and docking simulations. KEY RESULTS In vivo, catalpol treatment significantly improved adriamycin-induced kidney pathological changes and decreased the number of apoptotic cells. In vitro, catalpol markedly decreased the intracellular accumulation of adriamycin and reduced the calcium ion level in podocytes and then attenuated apoptosis. Importantly, the regulatory effects of catalpol on sirtuin 1 (SIRT1), multidrug resistance-associated protein 2 (MRP2), and the TRPC6 channel were mostly abolished after incubation with SIRT1 siRNA or the SIRT1-specific inhibitor EX527. Furthermore, docking simulations showed that catalpol efficiently oriented itself in the active site of SIRT1, indicating a higher total binding affinity score than that of other SIRT1 activators, such as resveratrol, SRT2104, and quercetin. CONCLUSION AND IMPLICATIONS Taken together, our results suggest that catalpol exhibits strong protective effects against adriamycin-induced nephropathy by inducing SIRT1-mediated inhibition of TRPC6 expression and enhancing MRP2 expression.
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Affiliation(s)
- Jiangnan Zhang
- Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning, China
| | - Ran Bi
- Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning, China
| | - Qiang Meng
- Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning, China.,Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning Dalian Medical University, Dalian, Liaoning, China
| | - Changyuan Wang
- Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning, China.,Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning Dalian Medical University, Dalian, Liaoning, China
| | - Xiaokui Huo
- Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning, China.,Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning Dalian Medical University, Dalian, Liaoning, China
| | - Zhihao Liu
- Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning, China.,Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning Dalian Medical University, Dalian, Liaoning, China
| | - Chong Wang
- Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning, China.,Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning Dalian Medical University, Dalian, Liaoning, China
| | - Pengyuan Sun
- Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning, China.,Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning Dalian Medical University, Dalian, Liaoning, China
| | - Huijun Sun
- Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning, China.,Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning Dalian Medical University, Dalian, Liaoning, China
| | - Xiaodong Ma
- Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning, China.,Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning Dalian Medical University, Dalian, Liaoning, China
| | - Jingjing Wu
- Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning, China.,Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning Dalian Medical University, Dalian, Liaoning, China
| | - Kexin Liu
- Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning, China.,Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning Dalian Medical University, Dalian, Liaoning, China
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Wang Y, Xu X, Hu P, Jia N, Ji S, Yuan H. Effect of Toll-Like Receptor 4/Myeloid Differentiation Factor 88 Inhibition by Salvianolic Acid B on Neuropathic Pain After Spinal Cord Injury in Mice. World Neurosurg 2019; 132:e529-e534. [PMID: 31449993 DOI: 10.1016/j.wneu.2019.08.086] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2019] [Revised: 08/12/2019] [Accepted: 08/14/2019] [Indexed: 01/23/2023]
Abstract
BACKGROUND Spinal cord injury (SCI) is a common type of injury, and about half of patients affected by SCI will suffer from neuropathic pain within a year after injury. However, the treatment effect of neuropathic pain is far from satisfactory. Our study attempted to reveal whether salvianolic acid B (SalB) could relieve the neuropathic pain caused by SCI in mice by inhibiting the Toll-like receptor 4 (TLR4)/Myeloid differentiation factor 88 (MyD88) pathway. METHODS The mice were randomly divided into a sham group, model group, high-dose treatment group, and low-dose treatment group. The high- and low-dose groups received varying doses of SalB after modeling. RESULTS The increase of pain sensitivity was evaluated by detecting paw withdrawal mechanical threshold and withdrawal thermal latency. Messenger RNA and protein expression levels of TLR4 and myD88 were detected by using quantitative reverse-transcription polymerase chain reaction and western blot, respectively. Compared with the model group, there was a significant reduction in paw withdrawal mechanical threshold and withdrawal thermal latency after SalB treatment. CONCLUSIONS SalB reduced the release of tumor necrosis factor-α and substance P by inhibiting the TLR4/MyD88 pathway in the SCI mouse model. This not only resulted in lower pain, but also contributed to long-term relief of mechanical hyperalgesia.
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Affiliation(s)
- Yufeng Wang
- Department of Radiology, Nantong Hospital of Traditional Chinese Medicine, Jiangsu, China
| | - Xiaoqing Xu
- Department of Pain Medicine, Nantong Hospital of Traditional Chinese Medicine, Jiangsu, China
| | - Peipei Hu
- Department of Pain Medicine, Nantong Hospital of Traditional Chinese Medicine, Jiangsu, China
| | - Ning Jia
- Department of Acupuncture, Qidong People's Hospital, Jiangsu, China
| | - Shiliang Ji
- Department of Pharmacy, The Affiliated Suzhou Science and Technology Town Hospital of Nanjing Medical University, Suzhou, China
| | - Hongjie Yuan
- Department of Pain Medicine, Nantong Hospital of Traditional Chinese Medicine, Jiangsu, China.
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Luo Y, Feng Y, Song L, He GQ, Li S, Bai SS, Huang YJ, Li SY, Almutairi MM, Shi HL, Wang Q, Hong M. A network pharmacology-based study on the anti-hepatoma effect of Radix Salviae Miltiorrhizae. Chin Med 2019; 14:27. [PMID: 31406500 PMCID: PMC6685170 DOI: 10.1186/s13020-019-0249-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2019] [Accepted: 07/26/2019] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Radix Salviae Miltiorrhizae (RSM), a well-known traditional Chinese medicine, has been shown to inhibit tumorigenesis in various human cancers. However, the anticancer effects of RSM on human hepatocellular carcinoma (HCC) and the underlying mechanisms of action remain to be fully elucidated. METHODS In this study, we aimed to elucidate the underlying molecular mechanisms of RSM in the treatment of HCC using a network pharmacology approach. In vivo and in vitro experiments were also performed to validate the therapeutic effects of RSM on HCC. RESULTS In total, 62 active compounds from RSM and 72 HCC-related targets were identified through network pharmacological analysis. RSM was found to play a critical role in HCC via multiple targets and pathways, especially the EGFR and PI3K/AKT signaling pathways. In addition, RSM was found to suppress HCC cell proliferation, and impair cancer cell migration and invasion in vitro. Flow cytometry analysis revealed that RSM induced cell cycle G2/M arrest and apoptosis, and western blot analysis showed that RSM up-regulated the expression of BAX and down-regulated the expression of Bcl-2 in MHCC97-H and HepG2 cells. Furthermore, RSM administration down-regulated the expression of EGFR, PI3K, and p-AKT proteins, whereas the total AKT level was not altered. Finally, the results of our in vivo experiments confirmed the therapeutic effects of RSM on HCC in nude mice. CONCLUSIONS We provide an integrative network pharmacology approach, in combination with in vitro and in vivo experiments, to illustrate the underlying therapeutic mechanisms of RSM action on HCC.
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Affiliation(s)
- Yi Luo
- Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, 510405 China
| | - Yu Feng
- Department of Traumatology, General Hospital of Ningxia Medical University, Yinchuan, 750004 China
- Department of Orthopaedics and Traumatology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Lei Song
- Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, 510405 China
| | - Gan-Qing He
- Department of Gastroenterology, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 501260 China
| | - Sha Li
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Sha-Sha Bai
- Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, 510405 China
| | - Yu-Jie Huang
- Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, 510405 China
| | - Si-Ying Li
- Department of Pharmacology & Toxicology, University of Kansas, Lawrence, KS USA
| | | | - Hong-Lian Shi
- Department of Pharmacology & Toxicology, University of Kansas, Lawrence, KS USA
| | - Qi Wang
- Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, 510405 China
| | - Ming Hong
- Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, 510405 China
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Ma Z, Zhang B, Fan Y, Wang M, Kebebe D, Li J, Liu Z. Traditional Chinese medicine combined with hepatic targeted drug delivery systems: A new strategy for the treatment of liver diseases. Biomed Pharmacother 2019; 117:109128. [PMID: 31234023 DOI: 10.1016/j.biopha.2019.109128] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2019] [Revised: 06/12/2019] [Accepted: 06/12/2019] [Indexed: 12/18/2022] Open
Abstract
Liver diseases are clinically common and present a substantial public health issue. Many of the currently available drugs for the treatment of liver diseases suffer from limitations that include low hepatic distribution, lack of target effects, poor in vivo stability and adverse effects on other organs. Consequently, conventional treatment of hepatic diseases is ineffective. TCM is commonly used in the treatment of liver diseases worldwide, particularly in China, and has advantages over conventional therapy. HTDDS can be designed to enhance clinical efficacy in the treatment of liver diseases. We have conducted an extensive review of 335 studies reported since 1964. These included about 166 references involving the treatment of liver diseases with TCM (covering active components of TCM, single TCM and Chinese medicine formulas), 169 reports on HTDDS and background studies on liver-related diseases. Here we review the long history of TCM in the treatment of liver diseases.We have also reviewed the status of studies on active components of TCM using nanotechnology-based targeted delivery systems to provide support for further research and development of TCM-based targeted preparations for the treatment of liver disease.
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Affiliation(s)
- Zhe Ma
- Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China; Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China
| | - Bing Zhang
- Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China; Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China
| | - Yuqi Fan
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China; School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China
| | - Meng Wang
- Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China; Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China
| | - Dereje Kebebe
- Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China; Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China; School of Pharmacy, Institute of Health Sciences, Jimma University, Jimma, Ethiopia
| | - Jiawei Li
- Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China; Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China; School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China.
| | - Zhidong Liu
- Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China; Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China.
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Kong LZ, Chandimali N, Han YH, Lee DH, Kim JS, Kim SU, Kim TD, Jeong DK, Sun HN, Lee DS, Kwon T. Pathogenesis, Early Diagnosis, and Therapeutic Management of Alcoholic Liver Disease. Int J Mol Sci 2019; 20:ijms20112712. [PMID: 31159489 PMCID: PMC6600448 DOI: 10.3390/ijms20112712] [Citation(s) in RCA: 127] [Impact Index Per Article: 21.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2019] [Revised: 05/30/2019] [Accepted: 05/31/2019] [Indexed: 02/08/2023] Open
Abstract
Alcoholic liver disease (ALD) refers to the damages to the liver and its functions due to alcohol overconsumption. It consists of fatty liver/steatosis, alcoholic hepatitis, steatohepatitis, chronic hepatitis with liver fibrosis or cirrhosis, and hepatocellular carcinoma. However, the mechanisms behind the pathogenesis of alcoholic liver disease are extremely complicated due to the involvement of immune cells, adipose tissues, and genetic diversity. Clinically, the diagnosis of ALD is not yet well developed. Therefore, the number of patients in advanced stages has increased due to the failure of proper early detection and treatment. At present, abstinence and nutritional therapy remain the conventional therapeutic interventions for ALD. Moreover, the therapies which target the TNF receptor superfamily, hormones, antioxidant signals, and MicroRNAs are used as treatments for ALD. In particular, mesenchymal stem cells (MSCs) are gaining attention as a potential therapeutic target of ALD. Therefore, in this review, we have summarized the current understandings of the pathogenesis and diagnosis of ALD. Moreover, we also discuss the various existing treatment strategies while focusing on promising therapeutic approaches for ALD.
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Affiliation(s)
- Ling-Zu Kong
- Laboratory of Animal Genetic Engineering and Stem Cell Biology, Advanced Convergence Technology and Science, Jeju National University, Jeju 63243, Korea.
- Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea.
| | - Nisansala Chandimali
- Laboratory of Animal Genetic Engineering and Stem Cell Biology, Advanced Convergence Technology and Science, Jeju National University, Jeju 63243, Korea.
- Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea.
| | - Ying-Hao Han
- Department of Disease Model Animal Research Center, College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing 163319, China.
| | - Dong-Ho Lee
- Primate Resources Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Jeongeup-si, Jeonbuk 56216, Korea.
| | - Ji-Su Kim
- Primate Resources Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Jeongeup-si, Jeonbuk 56216, Korea.
| | - Sun-Uk Kim
- Futuristic Animal Resource & Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju-si, Chungcheongbuk-do 28116, Korea.
| | - Tae-Don Kim
- Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea.
| | - Dong Kee Jeong
- Laboratory of Animal Genetic Engineering and Stem Cell Biology, Advanced Convergence Technology and Science, Jeju National University, Jeju 63243, Korea.
- Subtropical/Tropical Organism Gene Bank, Jeju National University, Jeju 63243, Korea.
| | - Hu-Nan Sun
- Department of Disease Model Animal Research Center, College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing 163319, China.
- Subtropical/Tropical Organism Gene Bank, Jeju National University, Jeju 63243, Korea.
| | - Dong Sun Lee
- Subtropical/Tropical Organism Gene Bank, Jeju National University, Jeju 63243, Korea.
- Department of Biotechnology, College of Applied Life Science, Jeju National University, Jeju 63243, Korea.
| | - Taeho Kwon
- Primate Resources Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Jeongeup-si, Jeonbuk 56216, Korea.
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Li X, Liu Y, Yue W, Tan Y, Wang H, Zhang L, Chen J. A Compound of Chinese Herbs Protects against Alcoholic Liver Fibrosis in Rats via the TGF- β1/Smad Signaling Pathway. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2019; 2019:9121347. [PMID: 31118972 PMCID: PMC6500606 DOI: 10.1155/2019/9121347] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/08/2019] [Revised: 03/11/2019] [Accepted: 03/31/2019] [Indexed: 02/06/2023]
Abstract
Alcoholic liver fibrosis (ALF) has become a major public health concern owing to its health impacts and the lack of effective treatment strategies for the disease. In this study, we investigated the effect of a compound composed of Chinese herbs Pueraria lobata (Willd.), Salvia miltiorrhiza, Schisandra chinensis, and Silybum marianum on ALF. An ALF model was established. Rats were fed with modified Lieber-Decarli alcohol liquid diet and injected with trace CCl4 at late stage. The rats were then treated with several doses of the compound. Biochemical and fibrosis-relevant parameters were measured from the sera obtained from the rats. Liver tissues were obtained for hematoxylin and eosin and Masson's trichrome staining. Matrix metalloproteinase-13 and tissue inhibitor of metalloproteinase-1 were determined by immunohistochemistry assays. The mRNA and protein expression levels of transforming growth factor-β1 (TGF-β1), Smad2, Smad3, and Smad7 on the livers were also measured by quantitative polymerase chain reaction and Western blot. Results showed that the compound treatment alleviated pathological lesions in the liver, decreased the serum levels of hyaluronan, laminin, and hydroxyproline, and diminished the expression of hepatic tissue inhibitor of metalloproteinase-1. Compound treatment also increased hepatic matrix metalloproteinase-13 expression and inhibited the TGF-β1/Smad signaling pathway. In conclusion, the compound has a protective effect against ALF in rats, and an underlying mechanism is involved in the TGF-β1/Smad signaling pathway.
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Affiliation(s)
- Xiaomeng Li
- West China School of Public Health and West China fourth Hospital, Sichuan University, Chengdu, China
- Food Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province, Chengdu, China
| | - Yunjie Liu
- West China School of Public Health and West China fourth Hospital, Sichuan University, Chengdu, China
- Food Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province, Chengdu, China
| | - Wuyang Yue
- West China School of Public Health and West China fourth Hospital, Sichuan University, Chengdu, China
- Food Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province, Chengdu, China
| | - Yuefeng Tan
- West China School of Public Health and West China fourth Hospital, Sichuan University, Chengdu, China
- Food Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province, Chengdu, China
| | - He Wang
- West China School of Public Health and West China fourth Hospital, Sichuan University, Chengdu, China
- Food Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province, Chengdu, China
| | - Lishi Zhang
- West China School of Public Health and West China fourth Hospital, Sichuan University, Chengdu, China
- Food Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province, Chengdu, China
| | - Jinyao Chen
- West China School of Public Health and West China fourth Hospital, Sichuan University, Chengdu, China
- Food Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province, Chengdu, China
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Zhang HY, Wang HL, Zhong GY, Zhu JX. Molecular mechanism and research progress on pharmacology of traditional Chinese medicine in liver injury. PHARMACEUTICAL BIOLOGY 2018; 56:594-611. [PMID: 31070528 PMCID: PMC6282438 DOI: 10.1080/13880209.2018.1517185] [Citation(s) in RCA: 53] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/29/2018] [Revised: 07/27/2018] [Accepted: 08/21/2018] [Indexed: 05/09/2023]
Abstract
CONTEXT Liver disease is a common threat to human health, caused by a variety of factors that damage the liver. Recent studies have shown that active ingredients (for example: flavonoids, saponins, acids, phenols, and alkaloids) from Traditional Chinese Medicine (TCM) can have hepatoprotective benefits, which represents an attractive source of drug discovery for treating liver injury. OBJECTIVE We reviewed recent contributions on the chemically induced liver injury, immunological liver damage, alcoholic liver injury, and drug-induced liver injury, in order to summarize the research progress in molecular mechanism and pharmacology of TCM, and provides a comprehensive overview of new TCM treatment strategies for liver disease. MATERIALS AND METHODS Relevant literature was obtained from scientific databases such as Pubmed, Web of Science. and CNKI databases on ethnobotany and ethnomedicines (from January 1980 to the end of May 2018). The experimental studies involving the antihepatic injury role of the active agents from TCM and the underlying mechanisms were identified. The search terms included 'liver injury' or 'hepatic injury', and 'traditional Chinese medicine', or 'herb'. RESULTS A number of studies revealed that the active ingredients of TCM exhibit potential therapeutic benefits against liver injury, while the underlying mechanisms appear to contribute to the regulation of inflammation, oxidant stress, and pro-apoptosis signaling pathways. DISCUSSION AND CONCLUSIONS The insights provided in this review will help further exploration of botanical drugs in the development of liver injury therapy via study on the effective components of TCM.
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Affiliation(s)
- Hong Yang Zhang
- Research Center of Traditional Chinese Medicine Resources and Minority Medicine, Jiangxi University of Traditional Chinese Medicine, Nan Chang, China
| | - Hong Ling Wang
- Research Center of Traditional Chinese Medicine Resources and Minority Medicine, Jiangxi University of Traditional Chinese Medicine, Nan Chang, China
| | - Guo Yue Zhong
- Research Center of Traditional Chinese Medicine Resources and Minority Medicine, Jiangxi University of Traditional Chinese Medicine, Nan Chang, China
| | - Ji Xiao Zhu
- Research Center of Traditional Chinese Medicine Resources and Minority Medicine, Jiangxi University of Traditional Chinese Medicine, Nan Chang, China
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Piao C, Li Z, Ding J, Kong D. Analysis of BMSCs-intervened viscoelasticity of sciatic nerve in rats with chronic alcoholic intoxication 1. Acta Cir Bras 2018; 33:935-944. [PMID: 30484503 DOI: 10.1590/s0102-865020180100000008] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2018] [Accepted: 09/10/2018] [Indexed: 12/13/2022] Open
Abstract
PURPOSE To investigate the impact of bone mesenchymal stem cells (BMSCs) intervention on the viscoelasticity of sciatic nerve in rats with chronic alcohol intoxication (CAI). METHODS The CAI rat models were prepared, divided into model groups, and treated with either BMSCs or basic fibroblast growth factor (bFGF). Then the rats underwent electrophysiological test and the serum levels of malondialdehyde (MDA), superoxide dismutase (SOD), and metallothionein (MT) were measured. Histological observation, stress relaxation test, and creep test were performed for the sciatic nerve of the CAI model in each group. RESULTS The MDA level of group BMSC was significantly lower (p<0.05) than that of groups MOD (the CIA model) and bFGF. The SOD and MT levels were higher in group BMSC than in groups MOD and bFGF (p<0.05). The motor nerve conduction velocity and amplitude were higher in group BMSC than in groups MOD and bFGF (p<0.05). The amounts of 7200s stress reduction and 7200 s strain increase of the sciatic nerve in group BMSC were greater than those in groups bFGF and MOD (p<0.05). CONCLUSION Bone mesenchymal stem cells can improve the metabolism of free radicals, restore the tissue morphology and viscoelasticity of the chronic alcohol intoxication animal model, and positively affect the repairing of the injured sciatic nerve.
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Affiliation(s)
- Chengdong Piao
- PhD, Department of Orthopaedics, Second Hospital of Jilin University, China. Conception and design of the study
| | - Zhengwei Li
- PhD, Department of Orthopaedics, Second Hospital of Jilin University, China. Histopathological examinations
| | - Jie Ding
- Master, Department of Stomatology, Affiliated Hospital of Changchun University of Chinese Medicine, China. Acquisition of data
| | - Daliang Kong
- PhD, Department of Orthopaedics, China-Japan Union Hospital, Jilin University, China. Technical procedures, analysis of data
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Protective Effects of Taraxasterol against Ethanol-Induced Liver Injury by Regulating CYP2E1/Nrf2/HO-1 and NF- κB Signaling Pathways in Mice. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2018; 2018:8284107. [PMID: 30344887 PMCID: PMC6174809 DOI: 10.1155/2018/8284107] [Citation(s) in RCA: 134] [Impact Index Per Article: 19.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/26/2018] [Revised: 08/07/2018] [Accepted: 08/15/2018] [Indexed: 01/01/2023]
Abstract
Taraxasterol, a pentacyclic-triterpene compound, is one of the main active components isolated from the traditional Chinese medicinal herb Taraxacum. The objective of this study is to evaluate the protective effects of taraxasterol and its possible underlying mechanisms against ethanol-induced liver injury in mice. ICR mice were fed with Lieber-DeCarli diet containing 5% ethanol for 10 d and then challenged with a single dose of 20% ethanol (5 g/kg BW) by intragastric administration. The mice were intragastrically treated daily with taraxasterol (2.5, 5, and 10 mg/kg). Tiopronin was used as a positive control. The liver index was calculated, and the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in sera were detected. The contents of reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) and the activity of superoxide dismutase (SOD) in the livers were measured. The histopathological changes of liver tissues were observed by hematoxylin and eosin (H&E) staining. The protein expression levels of hepatic cytochrome P450 2E1 (CYP2E1), nuclear factor erythroid 2-related factor 2 (Nrf2), antioxidant protein heme oxygenase-1 (HO-1), and nuclear factor-kappa B (NF-κB) signaling pathway in liver tissues were detected by immunohistochemistry and Western blot methods. Taraxasterol significantly reduced the ethanol-induced increases of liver index, ALT, AST, and TG levels in sera and TG and MDA contents in the livers and hepatic ROS production and suppressed the ethanol-induced decreases of hepatic GSH level and SOD activity. Taraxasterol also significantly inhibited the secretion of proinflammatory cytokines TNF-α and IL-6 induced by ethanol. In addition, taraxasterol improved the liver histopathological changes in mice with ethanol-induced liver injury. Further studies revealed that taraxasterol significantly inhibited the ethanol-induced upregulation of CYP2E1, increased the ethanol-induced downregulation of Nrf2 and HO-1, and inhibited the degradation of inhibitory kappa Bα (IκBα) and the expression level of NF-κB p65 in liver tissues of ethanol-induced mice. These findings suggest that taraxasterol possesses the potential protective effects against ethanol-induced liver injury in mice by exerting antioxidative stress and anti-inflammatory response via CYP2E1/Nrf2/HO-1 and NF-κB signaling pathways.
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Qin FY, Cheng LZ, Yan YM, Liu BH, Cheng YX. Choushenosides A-C, three dimeric catechin glucosides from Codonopsis pilosula collected in Yunnan province, China. PHYTOCHEMISTRY 2018; 153:53-57. [PMID: 29864628 DOI: 10.1016/j.phytochem.2018.05.012] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/07/2017] [Revised: 05/12/2018] [Accepted: 05/17/2018] [Indexed: 06/08/2023]
Abstract
Choushenosides A-C, three dimeric catechin glucosides, were isolated from the roots of Codonopsis pilosula cultivated at high elevations in Yunnan province of the People's Republic of China. The structures of these substances were determined by using spectroscopic and chemical methods. Biological evaluation showed that choushenoside C is a dose-dependent inhibitor of SIRT1.
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Affiliation(s)
- Fu-Ying Qin
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, People's Republic of China; University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China
| | - Li-Zhi Cheng
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, People's Republic of China; Guangdong Key Laboratory for Genome Stability & Disease Prevention, School of Pharmaceutical Sciences, School of Medicine, Shenzhen University Health Science Center, Shenzhen 518060, People's Republic of China
| | - Yong-Ming Yan
- Guangdong Key Laboratory for Genome Stability & Disease Prevention, School of Pharmaceutical Sciences, School of Medicine, Shenzhen University Health Science Center, Shenzhen 518060, People's Republic of China
| | - Bao-Hua Liu
- Guangdong Key Laboratory for Genome Stability & Disease Prevention, School of Pharmaceutical Sciences, School of Medicine, Shenzhen University Health Science Center, Shenzhen 518060, People's Republic of China.
| | - Yong-Xian Cheng
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, People's Republic of China; Guangdong Key Laboratory for Genome Stability & Disease Prevention, School of Pharmaceutical Sciences, School of Medicine, Shenzhen University Health Science Center, Shenzhen 518060, People's Republic of China; School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450008, People's Republic of China.
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Song J, Zhang W, Wang J, Yang H, Zhao X, Zhou Q, Wang H, Li L, Du G. Activation of Nrf2 signaling by salvianolic acid C attenuates NF‑κB mediated inflammatory response both in vivo and in vitro. Int Immunopharmacol 2018; 63:299-310. [PMID: 30142530 DOI: 10.1016/j.intimp.2018.08.004] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2018] [Revised: 08/03/2018] [Accepted: 08/03/2018] [Indexed: 01/13/2023]
Abstract
Neurodegenerative diseases are closely related to neuroinflammation. Drugs targeting inflammation have been proved to be effective in many animal models. Salvianolic acid C (SalC) is a compound isolated from Salvia miltiorrhiza Bunge, a plant with reported effects of inhibiting inflammation. However, the anti-inflammation effects and biological mechanisms of SalC on LPS-stimulated neuroinflammation remain unknown. The aim of this paper was to study its protective effects and its anti-inflammation mechanisms. LPS was used both in vivo and in vitro to induce neuroinflammation in SD rats and microglia cells. MTT assay was carried out to detect cell viability. The levels of TNF‑α, IL‑1β, IL‑6, IL‑10 and PGE2 were detected by ELISA method. The expressions of p‑AMPK, p‑NF‑κB p65, p‑IκBα, Nrf2, HO‑1 and NQO1 proteins were examined by Western blot analysis. The nuclear translocation of NF‑κB p65 was studied by immunofluorescence assay. The specific Nrf2 siRNA was used to clarify the interaction between Nrf2 and NF‑κB p65. The AMPK inhibitor Compound C was used study the upstream protein of Nrf2. Results showed that LPS induced the overexpression of inflammatory cytokines and mediated the phosphorylation and nuclear translocation of NF‑κB p65 in rat brains and microglia cells. SalC reversed the inflammatory response induced by LPS and inhibited the NF‑κB activation. SalC also upregulated the expression of p‑AMPK, Nrf2, HO‑1 and NQO1. But the anti-inflammation and NF‑κB inhibition effects of SalC were attenuated by transfection with specific Nrf2 siRNA or interference with the potent AMPK inhibitor Compound C. In conclusion, SalC inhibited LPS-induced inflammatory response and NF‑κB activation through the activation of AMPK/Nrf2 signaling both in vivo and in vitro.
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Affiliation(s)
- Junke Song
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Beijing Key Laboratory of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wen Zhang
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Beijing Key Laboratory of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jinhua Wang
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Beijing Key Laboratory of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Haiguang Yang
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Beijing Key Laboratory of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiaoyue Zhao
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Beijing Key Laboratory of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Qimeng Zhou
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Beijing Key Laboratory of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Haigang Wang
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Beijing Key Laboratory of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Li Li
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Beijing Key Laboratory of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Guanhua Du
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Beijing Key Laboratory of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
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Zhang T, Zhong S, Wang Y, Dong S, Guan T, Hou L, Xing X, Zhang J, Li T. In vitro and in silico perspectives on estrogenicity of tanshinones from Salvia miltiorrhiza. Food Chem 2018; 270:281-286. [PMID: 30174047 DOI: 10.1016/j.foodchem.2018.07.098] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2018] [Revised: 07/14/2018] [Accepted: 07/16/2018] [Indexed: 12/30/2022]
Abstract
This work aims to investigate the structure-activity relationship for binding and activation of human estrogen receptor α ligand binding domain (hERα-LBD) with tanshinones by a combination of in vitro and in silico approaches. The recombinant hERα-LBD was expressed in E. coli strain. The direct binding interactions of tanshinones with hERα-LBD and their ERα agonistic potency were investigated by fluorescence polarization (FP) and reporter gene assays, respectively. FP assay suggested that the tested tanshinones can bind to hERα-LBD as affinity ligands. Tanshinones acted as agonists of hERα as demonstrated by transactivation of estrogen response element (ERE) in transiently transfected MCF-7 cells and by molecular docking of these compounds into the hydrophobic binding pocket of hERα-LBD. Interestingly, comparison of the calculated binding energies versus Connolly solvent-excluded volume and experimental binding affinities showed a good correlation. This work may provide insight into chemical and pharmacological characterization of novel bioactive compounds from Salvia miltiorrhiza.
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Affiliation(s)
- Tiehua Zhang
- College of Food Science and Engineering, Jilin University, Changchun 130062, China
| | - Shuning Zhong
- College of Food Science and Engineering, Jilin University, Changchun 130062, China
| | - Yongjun Wang
- Institute of Agricultural Resources and Environment, Jilin Academy of Agricultural Sciences, Changchun 130033, China
| | - Shuyue Dong
- College of Food Science and Engineering, Jilin University, Changchun 130062, China
| | - Tianzhu Guan
- College of Food Science and Engineering, Jilin University, Changchun 130062, China
| | - Ligang Hou
- Institute of Agricultural Resources and Environment, Jilin Academy of Agricultural Sciences, Changchun 130033, China
| | - XiaoJia Xing
- Institute of Agricultural Resources and Environment, Jilin Academy of Agricultural Sciences, Changchun 130033, China
| | - Jie Zhang
- College of Food Science and Engineering, Jilin University, Changchun 130062, China.
| | - Tiezhu Li
- College of Food Science and Engineering, Jilin University, Changchun 130062, China.
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Shi M, Huang F, Deng C, Wang Y, Kai G. Bioactivities, biosynthesis and biotechnological production of phenolic acids in Salvia miltiorrhiza. Crit Rev Food Sci Nutr 2018; 59:953-964. [PMID: 29746788 DOI: 10.1080/10408398.2018.1474170] [Citation(s) in RCA: 167] [Impact Index Per Article: 23.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Salvia miltiorrhiza (Danshen in Chinese), is a well-known traditional Chinese medicinal plant, which is used as not only human medicine but also health-promotion food. Danshen has been extensively used for the treatment of various cardiovascular and cerebrovascular diseases. As a major group of bioactive constituents from S. miltiorrhiza, water-soluble phenolic acids such as salvianolic acid B possessed good bioactivities including antioxidant, anti-inflammatory, anti-cancer and other health-promoting activities. It is of significance to improve the production of phenolic acids by modern biotechnology approaches to meet the increasing market demand. Significant progresses have been made in understanding the biosynthetic pathway and regulation mechanism of phenolic acids in S.miltiorrhiza, which will facilitate the process of targeted metabolic engineering or synthetic biology. Furthermore, multiple biotechnology methods such as in vitro culture, elicitation, hairy roots, endophytic fungi and bioreactors have been also used to obtain pharmaceutically active phenolic acids from S. miltiorrhiza. In this review, recent advances in bioactivities, biosynthetic pathway and biotechnological production of phenolic acid ingredients were summarized and future prospective was also discussed.
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Affiliation(s)
- Min Shi
- a Laboratory of Medicinal Plant Biotechnology, College of pharmacy, Zhejiang Chinese Medical University , Hangzhou , Zhejiang , People's Republic of China
| | - Fenfen Huang
- b Institute of Plant Biotechnology, Development Center of Plant Germplasm Resources, College of Life and Environment Sciences, Shanghai Normal University , Shanghai , People's Republic of China
| | - Changping Deng
- b Institute of Plant Biotechnology, Development Center of Plant Germplasm Resources, College of Life and Environment Sciences, Shanghai Normal University , Shanghai , People's Republic of China
| | - Yao Wang
- b Institute of Plant Biotechnology, Development Center of Plant Germplasm Resources, College of Life and Environment Sciences, Shanghai Normal University , Shanghai , People's Republic of China
| | - Guoyin Kai
- a Laboratory of Medicinal Plant Biotechnology, College of pharmacy, Zhejiang Chinese Medical University , Hangzhou , Zhejiang , People's Republic of China.,b Institute of Plant Biotechnology, Development Center of Plant Germplasm Resources, College of Life and Environment Sciences, Shanghai Normal University , Shanghai , People's Republic of China
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Li J, Liu M, Yu H, Wang W, Han L, Chen Q, Ruan J, Wen S, Zhang Y, Wang T. Mangiferin Improves Hepatic Lipid Metabolism Mainly Through Its Metabolite-Norathyriol by Modulating SIRT-1/AMPK/SREBP-1c Signaling. Front Pharmacol 2018; 9:201. [PMID: 29563875 PMCID: PMC5850072 DOI: 10.3389/fphar.2018.00201] [Citation(s) in RCA: 55] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2018] [Accepted: 02/22/2018] [Indexed: 12/30/2022] Open
Abstract
Objective: Mangiferin (MGF) is a natural xanthone, with regulation effect on lipid metabolism. However, the molecular mechanism remains unclear. We purposed after oral administration, MGF is converted to its active metabolite(s), which contributes to the effects on lipid metabolism. Methods: KK-Ay mice were used to validate the effects of MGF on lipid metabolic disorders. Liver biochemical indices and gene expressions were determined. MGF metabolites were isolated from MGF administrated rat urine. Mechanism studies were carried out using HepG2 cells treated by MGF and its metabolite with or without inhibitors or small interfering RNA (siRNA). Western blot and immunoprecipitation methods were used to determine the lipid metabolism related gene expression. AMP/ATP ratios were measured by HPLC. AMP-activated protein kinase (AMPK) activation were identified by homogeneous time resolved fluorescence (HTRF) assays. Results: MGF significantly decreased liver triglyceride and free fatty acid levels, increased sirtuin-1 (SIRT-1) and AMPK phosphorylation in KK-Ay mice. HTRF studies indicated that MGF and its metabolites were not direct AMPK activators. Norathyriol, one of MGF's metabolite, possess stronger regulating effect on hepatic lipid metabolism than MGF. The mechanism was mediated by activation of SIRT-1, liver kinase B1, and increasing the intracellular AMP level and AMP/ATP ratio, followed by AMPK phosphorylation, lead to increased phosphorylation level of sterol regulatory element-binding protein-1c. Conclusion: These results provided new insight into the molecular mechanisms of MGF in protecting against hepatic lipid metabolic disorders via regulating SIRT-1/AMPK pathway. Norathyriol showed potential therapeutic in treatment of non-alcoholic fatty liver disease.
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Affiliation(s)
- Jian Li
- Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Mengyang Liu
- Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Haiyang Yu
- Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Wei Wang
- Houston Methodist Hospital, Houston, TX, United States
| | - Lifeng Han
- Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Qian Chen
- Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Jingya Ruan
- Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Shaoshi Wen
- Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Yi Zhang
- Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Tao Wang
- Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
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Trifan A, Opitz SE, Josuran R, Grubelnik A, Esslinger N, Peter S, Bräm S, Meier N, Wolfram E. Is comfrey root more than toxic pyrrolizidine alkaloids? Salvianolic acids among antioxidant polyphenols in comfrey (Symphytum officinale L.) roots. Food Chem Toxicol 2018; 112:178-187. [DOI: 10.1016/j.fct.2017.12.051] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2017] [Revised: 12/21/2017] [Accepted: 12/22/2017] [Indexed: 12/28/2022]
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Shi X, Sun R, Zhao Y, Fu R, Wang R, Zhao H, Wang Z, Tang F, Zhang N, Tian X, Yao J. Promotion of autophagosome–lysosome fusion via salvianolic acid A-mediated SIRT1 up-regulation ameliorates alcoholic liver disease. RSC Adv 2018; 8:20411-20422. [PMID: 35541657 PMCID: PMC9080827 DOI: 10.1039/c8ra00798e] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2018] [Accepted: 05/17/2018] [Indexed: 12/20/2022] Open
Abstract
Autophagosome and lysosome fusion was restored by salvianolic acid A-mediated SIRT1 up-regulation and protected against chronic ethanol-induced liver injury.
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Yan XF, Zhao P, Ma DY, Jiang YL, Luo JJ, Liu L, Wang XL. Salvianolic acid B protects hepatocytes from H 2O 2 injury by stabilizing the lysosomal membrane. World J Gastroenterol 2017; 23:5333-5344. [PMID: 28839433 PMCID: PMC5550782 DOI: 10.3748/wjg.v23.i29.5333] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2017] [Revised: 03/27/2017] [Accepted: 05/09/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the capability of salvianolic acid B (Sal B) to protect hepatocytes from hydrogen peroxide (H2O2)/carbon tetrachloride (CCl4)-induced lysosomal membrane permeabilization. METHODS Cell Counting Kit-8 assay was used to measure cell viability. Apoptosis and death were assayed through flow cytometry. BrdU incorporation was used to detect cell proliferation. Serum alanine aminotransferase activity and liver malondialdehyde (MDA) content were measured. Liver histopathological changes were evaluated using hematoxylin-eosin staining. Lysosomal membrane permeability was detected with LysoTracker Green-labeled probes and acridine orange staining. The levels of protein carbonyl content (PCC), cathepsins (Cat)B/D, and lysosome-associated membrane protein 1 (LAMP1) were evaluated through western blotting. Cytosol CatB activity analysis was performed with chemiluminescence detection. The mRNA level of LAMP1 was evaluated through quantitative real-time polymerase chain reaction. RESULTS Results indicated that H2O2 induced cell injury/death. Sal B attenuated H2O2-induced cell apoptosis and death, restored the inhibition of proliferation, decreased the amount of PCC, and stabilized the lysosome membrane by increasing the LAMP1 protein level and antagonizing CatB/D leakage into the cytosol. CCl4 also triggered hepatocyte death. Furthermore, Sal B effectively rescued hepatocytes by increasing LAMP1 expression and by reducing lysosomal enzyme translocation to the cytosol. CONCLUSION Sal B protected mouse embryonic hepatocytes from H2O2/CCl4-induced injury/death by stabilizing the lysosomal membrane.
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Ding RB, Bao J, Deng CX. Emerging roles of SIRT1 in fatty liver diseases. Int J Biol Sci 2017; 13:852-867. [PMID: 28808418 PMCID: PMC5555103 DOI: 10.7150/ijbs.19370] [Citation(s) in RCA: 256] [Impact Index Per Article: 32.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2017] [Accepted: 04/19/2017] [Indexed: 12/11/2022] Open
Abstract
Fatty liver diseases, which are commonly associated with high-fat/calorie diet, heavy alcohol consumption and/or other metabolic disorder causes, lead to serious medical concerns worldwide in recent years. It has been demonstrated that metabolic homeostasis disruption is most likely to be responsible for this global epidemic. Sirtuins are a group of conserved nicotinamide adenine dinucleotide (NAD+) dependent histone and/or protein deacetylases belonging to the silent information regulator 2 (Sir2) family. Among seven mammalian sirtuins, sirtuin 1 (SIRT 1) is the most extensively studied one and is involved in both alcoholic and nonalcoholic fatty liver diseases. SIRT1 plays beneficial roles in regulating hepatic lipid metabolism, controlling hepatic oxidative stress and mediating hepatic inflammation through deacetylating some transcriptional regulators against the progression of fatty liver diseases. Here we summarize the latest advances of the biological roles of SIRT1 in regulating lipid metabolism, oxidative stress and inflammation in the liver, and discuss the potential of SIRT1 as a therapeutic target for treating alcoholic and nonalcoholic fatty liver diseases.
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Affiliation(s)
- Ren-Bo Ding
- Cancer Centre, Faculty of Health Sciences, University of Macau, Macau SAR 999078, China
| | - Jiaolin Bao
- Cancer Centre, Faculty of Health Sciences, University of Macau, Macau SAR 999078, China
| | - Chu-Xia Deng
- Cancer Centre, Faculty of Health Sciences, University of Macau, Macau SAR 999078, China
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