Salvianic acid A alleviates chronic alcoholic liver disease by inhibiting HMGB1 translocation via down‐regulating BRD4
| العنوان: | Salvianic acid A alleviates chronic alcoholic liver disease by inhibiting HMGB1 translocation via down‐regulating BRD4 |
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| المؤلفون: | Ran Yan, Ruimin Sun, Jihong Yao, Yanwen Lan, Ning Zhang, Yan Zhao, Ruiwen Wang, Zhanyu Wang, Wen Shan, Junyi Chu |
| المصدر: | Journal of Cellular and Molecular Medicine |
| بيانات النشر: | Wiley, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Alcoholic liver disease, Cirrhosis, medicine.medical_treatment, Down-Regulation, chemical and pharmacologic phenomena, Pharmacology, Protective Agents, HMGB1, Chronic liver disease, Pathogenesis, Mice, 03 medical and health sciences, 0302 clinical medicine, medicine, Animals, HMGB1 Protein, Rats, Wistar, Liver Diseases, Alcoholic, Cells, Cultured, Cell Nucleus, Inflammation, Liver injury, biology, business.industry, Nuclear Proteins, Original Articles, Cell Biology, medicine.disease, SAA, Rats, 030104 developmental biology, Cytokine, Liver, 030220 oncology & carcinogenesis, Lactates, biology.protein, Cytokines, BRD4, Molecular Medicine, Original Article, Steatohepatitis, business, Signal Transduction, Transcription Factors, alcoholic liver disease |
| الوصف: | 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. |
| تدمد: | 1582-4934 1582-1838 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::33c09734e9e99faf689470c667172db5 https://doi.org/10.1111/jcmm.15473 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....33c09734e9e99faf689470c667172db5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15824934 15821838 |
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