Baihe Wuyao decoction ameliorates CCl4-induced chronic liver injury and liver fibrosis in mice through blocking TGF-β1/Smad2/3 signaling, anti-inflammation and anti-oxidation effects. (5th December 2020)

• Record Type: Journal Article
• Authors: Chen, Yajing; Li, Ruofei; Hu, Nan; Yu, Chunping; Song, Hongyu; Li, Yida; Dai, Yujiao; Guo, Zhao; Li, Meng; Zheng, Yi; Guo, Zhiyi; Qi, Yajuan
• Is Part Of: Journal of ethnopharmacology. Volume 263(2020)
• Publication Date: 2020-12-05
• Subjects: Chronic liver injury -- Liver fibrosis -- Signaling pathway -- Anti-inflammation -- Anti-oxidation; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2020.113227
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: Baihe Wuyao decoction (BWD), a prescription of Traditional Chinese Medicines, composed of Lilium brownii var. viridulum Baker.(Lilii Bulbus) and Lindera aggregata (Sims) Kosterm. (Linderae Radix), has been used to treat epigastric pain and superficial gastritis for hundreds of years in China. Recently, some compounds obtained from Lilii Bulbus and Linderae Radix had active effects of hepatic protection or liver fibrosis alleviation. Thus, we aim to evaluate the effects of BWD on treatment of chronic liver injury and liver fibrosis induced by carbon tetrachloride (CCl4 ) and to elucidate the possible molecular mechanism. Materials and methods: Mice were treated with BWD (low, medium and high dose), diammonium glycyrrhizinate or vehicle by oral gavage once daily, simultaneously intraperitoneal injected with a single dose of CCl4 (1 μl/g body weight) twice a week for consecutive 6 weeks. Next, all mice were sacrificed after fasted 12 h, and serums and liver tissues were harvested for analysis. The hepatic injury was detected by serum biomarker assay, including aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The hepatic histology and collagen were illustrated by hematoxylin-eosin staining and Sirius red staining respectively. The antioxidant capacity of liver tissues was evaluated by the contents of superoxide dismutase (SOD) and malondialdehyde (MDA) in liver homogenization. The mRNA gene or protein expressions related to fibrosis, oxidative stress and inflammation molecules were performed by real-time quantitative PCR (RT-PCR) or Western-blot. Results: BWD exhibited a good hepatic protection with ameliorating liver histological changes, decreasing serum AST and ALT contents, and reducing hepatic fibrosis with stimulation ECMs (such as Collagen1 and Collagen3) degradation. BWD inhibited hepatic stellate cells (HSCs) activation, promoted matrix metalloproteinase-2 (MMP2), MMP9, and MMP12 while suppressing tissue inhibitors of matrix metalloproteinase-1 (TIMP1) expression, and blocked traditional fibrosis TGF-β1/Smad2/3 signal pathway. Moreover, BWD exhibited anti-inflammation effect proved by the reduction of liver Interleukin-1β (IL-1β), TNF-α, IL-11 mRNA levels and promoted anti-oxidation effects determined by inhibition of liver MDA and iNOS levels while promoting liver SOD and Mn-SOD. Conclusion: BWD ameliorates CCl4 -induced CLI and liver fibrosis which is correlated to its blocking TGF-β1/Smad2/3 signaling, anti-inflammation, and anti-oxidation effects. BWD, as a small traditional prescription, is a promising treatment for CLI and liver fibrosis through multiple pharmacological targets. Graphical abstract: Schematic diagram represents the role of BWD protecting against CCl4 -induced chronic liver injury through three pathways: anti-fibrosis, anti-oxidation, and anti-inflammation. Each of the three pathways is dotted, and the results are highlighted in in web version. In addition, the most important factors (the changes of free radicals in reduce oxidative stress pathway and the changes of ECM in anti-fibrosis pathway) are also marked with in web version. In each factor, "↑" represents positive change; "↓" represents negative change. Red represents the change after CCl4 action; blue represents the change after BWD action. Image 1