Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 7, 2024; 30(13): 1911-1925
Published online Apr 7, 2024. doi: 10.3748/wjg.v30.i13.1911
Inhibition of hepatitis B virus via selective apoptosis modulation by Chinese patent medicine Liuweiwuling Tablet
Fei-Lin Ge, Yan Yang, Lan-Lan Si, Yuan-Hua Li, Meng-Zhen Cao, Jun Wang, Zhao-Fang Bai, Zhi-Gang Ren, Xiao-He Xiao, Yan Liu
Fei-Lin Ge, Department of Chinese Medicine, State Key Laboratory of Antiviral Drugs, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
Fei-Lin Ge, Lan-Lan Si, Yuan-Hua Li, Meng-Zhen Cao, Zhao-Fang Bai, Xiao-He Xiao, Yan Liu, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
Yan Yang, College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400010, China
Jun Wang, Beijing Key Laboratory of Emerging Infectious Diseases, Peking University Ditan Teaching Hospital, Beijing 100015, China
Zhi-Gang Ren, Department of Infectious Diseases, State Key Laboratory of Antiviral Drugs, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
Co-first authors: Fei-Lin Ge and Yan Yang.
Co-corresponding authors: Yan Liu and Xiao-He Xiao.
Author contributions: Liu Y and Xiao XH made substantial contributions to the conception or design of the study; Ge FL and Yang Y were in charge of the acquisition, analysis and interpretation of data, and wrote the manuscript; Li YH, Cao MZ and Wang J participated in experiments related to cell and animal models; Bai ZF, Ren ZG and Si LL were responsible for revision of the manuscript. All authors finally read and approved the version to be published. Ge FL and Yang Y contributed equally to this work as co-first authors. The reasons are the following. First, the research was performed as a collaborative effort, and the designation of co-first authors authorship accurately reflects the distribution of responsibilities and burdens associated with the time and effort required to complete the study and the resultant paper. Second, co-first authors contributed efforts of equal substance throughout the research process. Liu Y and Xiao XH contributed equally to this work as co-corresponding authors. The reasons are the following. First, they played a key role in coordinating the research team. Second, they made a great contribution to the original innovation of the article. In summary, we believe that designating Ge FL and Yang Y as co-first authors, Liu Y and Xiao XH as co-corresponding authors is fitting for our manuscript as it accurately reflects our team’s collaborative spirit, equal contributions, and diversity.
Supported by National Natural Science Foundation of China, No. 81930110; The National Funded Postdoctoral Researcher Program of China, No. GZC20232406; Henan Province Traditional Chinese Medicine Science Research Project, No. 2023ZY3040; Henan Province Medical Science and Technology Research Plan Joint Construction Project, No. LHGJ20230233; and National Key Research and Development Program of China, No. 2022YFC2303103.
Institutional animal care and use committee statement: Our research had been approved by the Committee on the Ethics of Animal Experiments of the Fifth Medical Center of Chinese PLA General Hospital (Permit number: IACUC-2021-0009).
Conflict-of-interest statement: The authors of this manuscript having no conflicts of interest to disclose.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yan Liu, PhD, The Fifth Medical Center of Chinese PLA General Hospital, No. 100 Xisihuan Middle Road, Beijing 100039, China. liuyan5360@163.com
Received: October 10, 2023
Peer-review started: October 10, 2023
First decision: December 27, 2023
Revised: January 7, 2024
Accepted: February 25, 2024
Article in press: February 25, 2024
Published online: April 7, 2024
ARTICLE HIGHLIGHTS
Research background

Nucleoside/nucleotide analogs (NAs) are the most commonly-used anti-hepatitis B virus (HBV) agents. They effectively inhibit viral replication, whereas the suppressive effects are much weaker on HBV antigen and drug-resistant HBV. Therefore, it is very important and meaningful to find new drugs to make up for the deficiency of NAs. Liuweiwuling Tablet (LWWL) is a licensed Chinese patent medicine for anti-inflammation of chronic HBV infection. We previous found that LWWL has an anti-HBV effect in wild-type HBV model for the first time, but the mechanism is still unclear.

Research motivation

The objective of this study was to elucidate the scientific significance of LWWL’s antiviral advantages, in order to provide a reference for the clinical application of LWWL against HBV.

Research objectives

The study aimed to explore the potential mechanism of anti-HBV, and further comprehensively evaluate its anti-HBV effect in drug-resistant HBV model.

Research methods

In vitro experiments utilized three HBV-replicating cell lines and three non-HBV-replicating cell lines, while an in vivo experiment involved a hydrodynamic injection-mediated mouse model with HBV replication. Transcriptomics and metabolomics were employed to investigate the underlying mechanisms.

Research results

Our study establishes the potent HBV-suppressive capability of the Chinese patent medicine LWWL. Furthermore, these suppressive effects surpassed those of tenofovir disoproxil fumarate in terms of antigen expression in both in vitro and in vivo. A foundational insight into the mechanism of LWWL’s anti-HBV action suggests its involvement in the regulation of selective apoptosis, selectively inducing apoptosis in HBV-replicating hepatic cells while not affecting non-HBV-replicating hepatic cells.

Research conclusions

The preliminary revelation in the anti-HBV pharmacological mechanism is that LWWL exerts a potent inhibitory impact on both wild-type and drug-resistant HBV, potentially involving a selective regulation of apoptosis. These findings offer novel insights into the anti-HBV activities of LWWL and present a novel mechanism for the development of anti-HBV medications.

Research perspectives

Novel anti-HBV drugs were developed by using a selective regulation of apoptosis mechanism.