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

Hong, Ming, Li, Sha, Tan, Hor, Cheung, Fan, Wang, Ning, Huang, Jihan, Feng, Yibin·2017·Molecules
DOI 10.3390/molecules22040632PMC PMC6154655
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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.

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Figure 1 Compound-target hepatotoxicity network of Xiao chai hu tang. This network represents a global view of the potential compounds (red triangles) and targets (blue rectangles) in XCHT, and it comprised 74 nodes (23 potential compounds and 51 potential targets) and 131 edges (compound-target interactions).
Figure 1 Compound-target hepatotoxicity network of Xiao chai hu tang. This network represents a global view of the potential compounds (red triangles) and targets (blue rectangles) in XCHT, and it comprised 74 nodes (23 potential compounds and 51 potential targets) and 131 edges (compound-target interactions).CC BY · PubMed Central
Figure 2 Compound-target network of Heshouwu that are associated with HILI. The red triangles are active compounds from Heshouwu and the blue rectangles represent potential hepatotoxic target genes, the grey lines represent the compound-target interaction. This network comprises 43 nodes (13 candidate compounds and 30 potential targets) and 62 edges (compound-target interactions).
Figure 2 Compound-target network of Heshouwu that are associated with HILI. The red triangles are active compounds from Heshouwu and the blue rectangles represent potential hepatotoxic target genes, the grey lines represent the compound-target interaction. This network comprises 43 nodes (13 candidate compounds and 30 potential targets) and 62 edges (compound-target interactions).CC BY · PubMed Central
Figure 3 Network pharmacology approach workflow in this study.
Figure 3 Network pharmacology approach workflow in this study.CC BY · PubMed Central

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Metadata

Authors
Hong, M., Li, S., Tan, H., Cheung, F., Wang, N., Huang, J., & Feng, Y.
Affiliations
  • School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
  • Shanghai University of Traditional Chinese Medicine, Shanghai, China
ORCID
Huang, Jihan
Venue
Molecules
Publisher
MDPI AG
Published
2017-04-14
Volume
22
Issue
4
Pages
632
ISSN
1420-3049
DOI
10.3390/molecules22040632
PMC
PMC6154655
Cited by
67
References
0
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)

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