Inhibition of hepatitis B virus via selective apoptosis modulation by Chinese patent medicine Liuweiwuling Tablet  

作　　者：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 

机构地区：[1]Department of Chinese Medicine,State Key Laboratory of Antiviral Drugs,The First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,Henan Province,China [2]The Fifth Medical Center of Chinese PLA General Hospital,Beijing 100039,China [3]College of Traditional Chinese Medicine,Chongqing Medical University,Chongqing 400010,China [4]Beijing Key Laboratory of Emerging Infectious Diseases,Peking University Ditan Teaching Hospital,Beijing 100015,China [5]Department of Infectious Diseases,State Key Laboratory of Antiviral Drugs,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,Henan Province,China

出　　处：《World Journal of Gastroenterology》2024年第13期1911-1925,共15页世界胃肠病学杂志（英文版）

基　　金：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;National Key Research and Development Program of China,No.2022YFC2303103.

摘　　要：BACKGROUND Liuweiwuling Tablet(LWWL)is a Chinese patent medicine approved for the treatment of chronic inflammation caused by hepatitis B virus(HBV)infection.Previous studies have indicated an anti-HBV effect of LWWL,specifically in terms of antigen inhibition,but the underlying mechanism remains unclear.AIM To investigate the potential mechanism of action of LWWL against HBV.METHODS In vitro experiments utilized three HBV-replicating and three non-HBV-replicating cell lines.The in vivo experiment involved a hydrodynamic injectionmediated mouse model with HBV replication.Transcriptomics and metabolomics were used to investigate the underlying mechanisms of action of LWWL.RESULTS In HepG2.1403F cells,LWWL(0.8 mg/mL)exhibited inhibitory effects on HBV DNA,hepatitis B surface antigen and pregenomic RNA(pgRNA)at rates of 51.36%,24.74%and 50.74%,respectively.The inhibition rates of LWWL(0.8mg/mL)on pgRNA/covalently closed circular DNA in HepG2.1403F,HepG2.2.15 and HepG2.A64 cells were 47.78%,39.51%and 46.74%,respectively.Integration of transcriptomics and metabolomics showed that the anti-HBV effect of LWWL was primarily linked to pathways related to apoptosis(PI3K-AKT,CASP8-CASP3 and P53 pathways).Apoptosis flow analysis revealed that the apoptosis rate in the LWWL-treated group was significantly higher than in the control group(CG)among HBV-replicating cell lines,including HepG2.2.15(2.92%±1.01%vs 6.68%±2.04%,P<0.05),HepG2.A64(4.89%±1.28%vs 8.52%±0.50%,P<0.05)and HepG2.1403F(3.76%±1.40%vs 7.57%±1.35%,P<0.05)(CG vs LWWL-treated group).However,there were no significant differences in apoptosis rates between the non-HBV-replicating HepG2 cells(5.04%±0.74%vs 5.51%±1.57%,P>0.05),L02 cells(5.49%±0.80%vs 5.48%±1.01%,P>0.05)and LX2 cells(6.29%±1.54%vs 6.29%±0.88%,P>0.05).TUNEL staining revealed a significantly higher apoptosis rate in the LWWL-treated group than in the CG in the HBVreplicating mouse model,while no noticeable difference in apoptosis rates between the two groups was observed in the non-HBV-replica

关 键 词：Hepatitis B virus Chinese patent medicine Antiviral activity Antiviral mechanism Selective apoptosis 

分 类 号：R512.62[医药卫生—内科学]