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. 2024 Jun 7;24(1):219.
doi: 10.1186/s12906-024-04517-y.

Unraveling the treatment effects of huanglian jiedu decoction on drug-induced liver injury based on network pharmacology, molecular docking and experimental validation

Yaochen Xie  1 , Shuchen Gong  1   2   3 , Lingkun Wang  1 , Zhaoxu Yang  1 , Chen Yang  1 , Guilin Li  1 , Huiyan Zha  1 , Shuying Lv  1 , Boneng Xiao  1   3 , Xiaoyu Chen  1 , Zhenning Di  4 , Qiaojun He  1   5   6 , Jincheng Wang  7   8   9 , Qinjie Weng  10   11   12   13
Affiliations

Unraveling the treatment effects of huanglian jiedu decoction on drug-induced liver injury based on network pharmacology, molecular docking and experimental validation

Yaochen Xie et al. BMC Complement Med Ther. .

Abstract

Huanglian Jiedu Decoction (HJD) is a well-known Traditional Chinese Medicine formula that has been used for liver protection in thousands of years. However, the therapeutic effects and mechanisms of HJD in treating drug-induced liver injury (DILI) remain unknown. In this study, a total of 26 genes related to both HJD and DILI were identified, which are corresponding to a total of 41 potential active compounds in HJD. KEGG analysis revealed that Tryptophan metabolism pathway is particularly important. The overlapped genes from KEGG and GO analysis indicated the significance of CYP1A1, CYP1A2, and CYP1B1. Experimental results confirmed that HJD has a protective effect on DILI through Tryptophan metabolism pathway. In addition, the active ingredients Corymbosin, and Moslosooflavone were found to have relative strong intensity in UPLC-Q-TOF-MS/MS analysis, showing interactions with CYP1A1, CYP1A2, and CYP1B1 through molecule docking. These findings could provide insights into the treatment effects of HJD on DILI.

Keywords: Drug-induced liver injury; Huanglian Jiedu Decoction; Molecule docking; Network pharmacology; Q-TOF; Tryptophan metabolism.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Fig. 1
Fig. 1
The relationship between DILI targets and active ingredients in HJD. (A) The Venn diagram of drug targets, disease targets and their overlapping during network construction process of HJD and DILI. (B) The network between the overlapped targets and their related active compounds in HJD
Fig. 2
Fig. 2
PPI network of the overlapped 26 potential targets that could be used in HJD for treating DILI
Fig. 3
Fig. 3
Pathway analysis of the protective effects HJD against DILI. (A) The most enriched pathways for KEGG; (B) The signaling transduction pathway of Tryptophan metabolism signaling pathway
Fig. 4
Fig. 4
GO enrichment analysis for the top 10 most significant terms in BP (A), CC (B), and MF (C)
Fig. 5
Fig. 5
Flow cytometry analysis for CYP1A1 (A-B), CYP1A2 (C-D), and CYP1B1 (E-F). Data are presented as **, p < 0.01; and ***, p < 0.001
Fig. 6
Fig. 6
Experimental validations of HJD treatment against DILI with three identical groups (Control, APAP, and APAP + HJD). (A) and (B) ALT and AST levels (n = 6 animals/group). (C) Representative H&E staining of liver where circled place indicates places of injury, scale bar: 300 μm. (D) Statistics of liver injury area (n = 3 animals/group); (E) Representative western blotting analysis of liver CYP1A1, CYP1A2, and CYP1B1 expression levels in mice liver (n = 3 animals/group), Original images of blots are shown in Fig. S1.; (F) Liver 5-HT level (n = 3 animals/group); (G-H) qRT-PCR analysis of Maoa and Maob in mice liver (n = 3 animals/group). Data are presented as ns, p > 0.05; *, p < 0.05; **,  p < 0.01; ***, p < 0.001 compared with Control group; #, p < 0.05; ##, p < 0.01; ###, p < 0.001 compared with APAP group
Fig. 7
Fig. 7
Molecule docking of active ingredients with potential targets. (A) The binding of CYP1A1 with Compound 70; (B) The binding of CYP1A2 with Compound 70; (C) The binding of CYP1B1 with Compound 83
Fig. 8
Fig. 8
UPLC-Q-TOF-MS/MS analysis of active ingredients in HJD. (A) and (B) The intensity of Compound 70 and 83, and its retention time in UPLC-Q-TOF-MS/MS analysis; (C) and (D) Corresponding secondary mass spectra of Compound 70 and 83
Fig. 9
Fig. 9
Graphical abstract of HJD treatment effect against APAP-induced liver injury
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