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. 2024 Dec:135:155915.
doi: 10.1016/j.phymed.2024.155915. Epub 2024 Aug 10.

Mechanism Research of QingReJieDu Formula for Treating Hepatitis B Virus Based on Network Pharmacology

Caixia Jia  1 , Hongxing Wu  1 , Aiqing Yang  2 , Aiping Chen  1 , Xueting Wang  3 , Shuqin Ding  4 , Baofeng Fan  1 , Gangqiao Zhou  5 , Zhihong Li  6 , Jianxin Chen  7
Affiliations

Mechanism Research of QingReJieDu Formula for Treating Hepatitis B Virus Based on Network Pharmacology

Caixia Jia et al. Phytomedicine. 2024 Dec.

Abstract

Background: Hepatitis B virus (HBV) is a DNA virus known to induce hepatitis and liver dysfunction, and is one of the main causes of liver cirrhosis and liver cancer. At present, there lacks a satisfactory optimal treatment plan for HBV in clinical practice, promoting the development of a novel Chinese formula, QingReJieDu Formula (QRJDF), as a potential solution.

Purpose: This study aims to explore the underlying mechanisms of QRJDF in the treatment of Hepatitis B virus (HBV) through a combination of network pharmacology and experimental validation.

Methods/study design: HepG2.2.15 cells were used to study the efficacy of QRJDF against HBV in vitro. Entecavir (ETV) was used as a positive control. Additionally, HBV transgenic mice served as subjects to study the in vivo efficacy of QRJDF against HBV, with serum and tissue samples analyzed post-euthanasia at 12 weeks to observe relevant indicators. UPLC-Q-TOF-MS technology was utilized to obtain the main ingredients in QRJDF. Network pharmacology was used to explore the potential ingredients and targets of QRJDF against HBV. Transcriptome sequencing was used to further explore the potential targets of QRJDF against HBV. Finally, integration of network pharmacology and transcriptomics results facilitated the screening of potential key targets and identification of potential pathways.

Results: QRJDF demonstrated anti-HBV effects in HepG2.2.15 cells, compared to ETV control, QRJDF was more efficient in inhibiting HBV antigen levels, although it was less efficient in inhibiting HBV DNA level. In addition, the antiviral effect was verified in HBV transgenic mice. Network pharmacology results found three major active anti-HBV ingredients from QRJDF. Network pharmacology and transcriptomics revealed that QRJDF could act on the TGFβ1/Smad4 signaling pathway.

Conclusion: The study comprehensively evaluated the efficacy in vivo and in vitro, and fully confirmed that QRJDF was a potential therapeutic agent for HBV. In addition, the transcriptome technology was verified, and the key targets and approaches of QRJDF against hepatitis B were screened in combination with network pharmacology, which provided research ideas for the follow-up research of antiviral Chinese medicine.

Keywords: Hepatitis B virus; Mechanism; Network pharmacology; QingReJieDu Formula; Transcriptome.

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Conflict of interest statement

Declaration of competing interest This manuscript has not been published or presented elsewhere in part or in entirety and is not under consideration by another journal. We have read and understood your journal's policies, and we believe that neither the manuscript nor the study violates any of these. All authors declare no conflicts of interest.

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