A Network-Based Pharmacology Study of the Herb-Induced Liver Injury Potential of Traditional Hepatoprotective Chinese Herbal Medicines.

Ming Hong,Yibin Feng,Jihan Huang,Hor Tan,Ning Wang,Fan Cheung,Sha Li

doi:10.3390/molecules22040632

Abstract

Herbal medicines are widely used for treating liver diseases and generally regarded as safe due to their extensive use in Traditional Chinese Medicine practice for thousands of years. However, in recent years, there have been increased concerns regarding the long-term risk of Herb-Induced Liver Injury (HILI) in patients with liver dysfunction. Herein, two representative Chinese herbal medicines: one—Xiao-Chai-Hu-Tang (XCHT)—a composite formula, and the other—Radix Polygoni Multiflori (Heshouwu)—a single herb, were analyzed by network pharmacology study. Based on the network pharmacology framework, we exploited the potential HILI effects of XCHT and Heshouwu by predicting the molecular mechanisms of HILI and identified the potential hepatotoxic ingredients in XCHT and Heshouwu. According to our network results, kaempferol and thymol in XCHT and rhein in Heshouwu exhibit the largest number of liver injury target connections, whereby CASP3, PPARG and MCL1 may be potential liver injury targets for these herbal medicines. This network pharmacology assay might serve as a useful tool to explore the underlying molecular mechanism of HILI. Based on the theoretical predictions, further experimental verification should be performed to validate the accuracy of the predicted interactions between herbal ingredients and protein targets in the future.

Highlights

Herb-Induced Liver injury (HILI) refers to herbal drug-driven liver injuries which are a cause of acute and chronic liver disease
Potential HILI Mechanisms of XCHT Predicted by Network Pharmacological Analysis
We have identified a total of 761 chemicals in XCHT

Summary

Introduction

Herb-Induced Liver injury (HILI) refers to herbal drug-driven liver injuries which are a cause of acute and chronic liver disease. Xiao-chai-hu-tang (XCHT), a Chinese herbal formula, is commonly used for treatment of chronic hepatitis and liver fibrosis in East Asian countries such as China, Japan and Korea. XCHT exhibits various pharmacological properties including anti-inflammation, antioxidant and anti-hepatic fibrosis [2,3]. XCHT has shown strong hepatoprotective effects in both basic and clinical studies by regulating the immune response in the context of hepatitis C viral infection [4,5]. There are currently ongoing clinical trials of XCHT for hepatitis C and liver cirrhosis at the University of California, at San Diego and the Memorial Sloan-Kettering Cancer Center in the Molecules 2017, 22, 632; doi:10.3390/molecules22040632 www.mdpi.com/journal/molecules

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