Amelioration of non-alcoholic steatohepatitis by Qushi Huayu decoction is associated with inhibition of the intestinal mitogen-activated protein kinase pathway |
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| Institution: | 1. Institute of Liver diseases, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, 528, Zhangheng Road, Shanghai, China;2. Institute of Clinical Pharmacology, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, 528, Zhangheng Road, Shanghai, China;3. Key Laboratory of Liver and Kidney Diseases (Shanghai University of Traditional Chinese Medicine), Ministry of Education, 528, Zhangheng Road, Shanghai, China;4. Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, 528, Zhangheng Road, Shanghai, China;1. Department of Clinical Pharmacology, Nanjing Drum Tower Hospital, Pharmacy Collage of Nanjing Medical University, Nanjing 210000, China;2. Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210000, China;3. Natural Products Unit, Medicinal and Aromatic Plants Department, Desert Research Centre, Cairo, Egypt;4. Department of Pharmacognosy, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt;5. Department of Pathology, Nanjing Drum Tower Hospital of Nanjing University Medical School, Nanjing 210000, China;6. Research Division of Clinical Pharmacology, The First Affiliated Hospital, Pharmacy College of Nanjing Medical University, Nanjing 210000, China;7. Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing 210000, China;1. Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian, Liaoning, China;2. Provincial Key Laboratory for Pharmacokinetics and Transport, Dalian, Liaoning, China |
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| Abstract: | BackgroundGut microbiota is increasingly recognized as the key participant in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) by translocation of its products, such as lipopolysaccharide (LPS), via the dysfunctional intestinal barrier. Qushi Huayu decoction (QHD), a traditional Chinese medicine, is developed specially for NAFLD and used in clinic in China for more than a decade and previously found to ameliorate non-alcoholic steatohepatitis (NASH) induced by high-fat diet (HFD) in mice accompanied with inhibited metabolic endotoxemia and hepatic LPS signalling.PurposeTo investigate the mechanism of LPS gut-leakage inhibition by QHD in NASH.MethodsEffects of QHD on gut microbioa and intestinal barrier were evaluated in NASH induced by HFD in mice. 16S rRNA sequencing is employed to analyse the gut microbiota composition. To identify the potential signalling pathway responsible for tight junction regulation, the colonic phosphoprotein profile is screened via the Phospho Explorer Antibody Array and verified in NASH, intestinal barrier dysfunctional mouse and Caco-2 cells.ResultsQHD ameliorates NASH accompanied with regulating the gut microbiota composition, protecting intestinal tight junctions and inhibiting LPS gut-leakage without decreasing the abundance of identified Gram-negative bacteria. The validated data of phosphorylated proteins suggested that mitogen-activated protein kinase (MAPK) pathway is predominantly responsible for the colonic tight junction regulation by QHD.ConclusionQHD inhibits LPS gut-leakage in NASH, which is associated with downregulation of intestinal MAPK pathway. |
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