1. Astragaloside Alleviates Hepatic Fibrosis Function via PAR2 Signaling Pathway in Diabetic Rats.
- Author
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Wang Z, Li Q, Xiang M, Zhang F, Wei D, Wen Z, and Zhou Y
- Subjects
- Alanine Transaminase metabolism, Animals, Aspartate Aminotransferases metabolism, Carbon Tetrachloride, Cyclic AMP-Dependent Protein Kinases genetics, Cyclic AMP-Dependent Protein Kinases metabolism, Diabetes Mellitus, Experimental chemically induced, Diabetes Mellitus, Experimental genetics, Diabetes Mellitus, Experimental pathology, Gene Expression Regulation, Interleukin-1beta genetics, Interleukin-1beta metabolism, Interleukin-6 genetics, Interleukin-6 metabolism, Liver Cirrhosis chemically induced, Liver Cirrhosis genetics, Liver Cirrhosis pathology, Male, Protein Kinase C-epsilon genetics, Protein Kinase C-epsilon metabolism, Rats, Rats, Sprague-Dawley, Receptor, PAR-2 antagonists & inhibitors, Receptor, PAR-2 metabolism, Signal Transduction, Streptozocin, Transforming Growth Factor beta1 metabolism, Tumor Necrosis Factor-alpha genetics, Tumor Necrosis Factor-alpha metabolism, Diabetes Mellitus, Experimental drug therapy, Liver Cirrhosis drug therapy, Receptor, PAR-2 genetics, Saponins pharmacology, Transforming Growth Factor beta1 genetics, Triterpenes pharmacology
- Abstract
Background/aims: Astragaloside (AGS) extracted from radix astragalin (Huangqi) has been considered to be beneficial to liver diseases. In this study, we examined the role played by AGS in alleviating hepatic fibrosis function via protease-activated receptor-2 (PAR2) mechanisms. We hypothesized that AGS affects PAR2 signaling pathway thereby improving hepatic function in rats with hepatic fibrosis induced by carbon tetrachloride (CCl4). We further hypothesized that AGS attenuates impaired hepatic function evoked by CCl4 to a greater degree in diabetic animals., Methods: ELISA and Western Blot analysis were used to examine PAR2 signaling pathway in diabetic CCl4-rats and non-diabetic CCl4-rats., Results: AGS inhibited the protein expression of PAR2 and its downstream pathway PKA and PKCɛ in CCl4-rats. Notably, the effects of AGS were greater in CCl4-rats with diabetes. AGS also significantly attenuated the CCl4-induced upregulations of pro-inflammatory cytokines, namely interleukin-1β, interleukin-6 and tumor necrosis factor-α accompanied with decreases of collagenic parameters such as hexadecenoic acid, laminin and hydroxyproline. Additionally, AGS improved the CCl4-induced exaggerations of liver index and functions including alanine aminotransferase, aspartate aminotransferase. Moreover, TGF-β1, a marker of hepatic fibrosis, was increased in CCl4-rats and AGS inhibited increases in TGF-β1 induced by CCl4., Conclusions: AGS alleviates hepatic fibrosis by inhibiting PAR2 signaling expression and its effects are largely enhanced in diabetic animals. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of hepatic fibrosis; and results of our study are likely to shed light on strategies for application of AGS because it has potentially greater therapeutic effectiveness for hepatic fibrosis in diabetes., (© 2017 The Author(s)Published by S. Karger AG, Basel.)
- Published
- 2017
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