Poria Attenuates Idiosyncratic Liver Injury Induced by Polygoni Multiflori Radix Praeparata.

Dan Gao,Jia-Bo Wang,Xiao-He Xiao,Wei-Wei Gao,Can Tu,Kui-Jun Zhao,Hai-Zhu Zhang,Ming Niu,Jing-Yao Pang,Yin Xiong,Chun-Yu Li,Cong-En Zhang

doi:10.3389/fphar.2016.00386

Abstract

The hepatotoxicity induced by Polygoni Multiflori Radix Praeparata (PM) has aroused great concern throughout the world. Hence, it is worthwhile to perform studies on the detoxification with the combined use of medicinal herbs based on the compatibility theory of traditional Chinese medicine. In this work, the rat model of PM/LPS-induced idiosyncratic liver injury was used. The effects of Poria, Licorice, and Panax notoginseng on rats of PM/LPS-induced liver injury were investigated respectively, hoping to find the most effective herbal medicine to reduce the hepatotoxicity. According to results of biochemical and histological tests, PM could induce the idiosyncratic hepatotoxicity of rats which presented modest inflammation triggered by non-injurious dose of lipopolysaccharide (LPS). We also found that the combined use of Poria and PM in the ratio of 1:2 could significantly ameliorate the PM/LPS-induced liver injury and systemic inflammation. Furthermore, UPLC/QTOF-MS-based metabolomics was performed to identify possible biomarkers and underlying biological pathways. Ten metabolites were expressed differentially among LPS, PM/LPS, and detoxification-treated groups in terms of PCA and OPLS-DA analysis, which could be potential biomarkers. MetaboAnalyst and pathway enrichment analysis revealed that alterations of these metabolites were primarily involved in three pathways: arginine and proline metabolism, primary bile acid biosynthesis and sphingolipid metabolism. This research provides systematic experimental evidences for the hepatoprotective effect of Poria against PM/LPS-induced liver injury for the first time. And these findings may help better understand the underlying mechanisms of pathophysiologic changes in PM/LPS-induced liver injury.

Highlights

Due to the limited effectiveness and/or undesirable side effects of standard medical practice, patients often turn to alternative medicines which are often believed to be safer and sometimes better as they are “natural” and “wellness” (Seeff et al, 2001; Bent and Ko, 2004)
Rats consuming these four herbs alone almost did not alter the liver function which was indicated by the similar values of plasma Alanine transaminase (ALT), AST, and total bile acid (TBA) compared to the control group (Ctr)
Afterwards, we further focused on studying the detoxification effect of PM-treated group (PM) + Poria co-treated with LPS (LPP), PM + Licorice with LPS (LPL), and PM + Panax notoginseng with LPS (LPN), respectively

Summary

Introduction

Due to the limited effectiveness and/or undesirable side effects of standard medical practice, patients often turn to alternative medicines which are often believed to be safer and sometimes better as they are “natural” and “wellness” (Seeff et al, 2001; Bent and Ko, 2004). The increasing popularity of traditional Chinese medicine (TCM) becomes a worldwide phenomenon. We found that PM could lead to the failure of liver microcirculation perfusion (Chang et al, 2014), while it is still difficult to establish the direct causal relationship between the hepatic injury and complex constituents even in one single herbal medicine. It might be more practical to find remedies to reduce the toxicity rather than delving too deep into possible causes of hepatic injury

Methods

Results

Conclusion