Hongxuan Tong , Jiale Zhang , Lijie Jiang , Rendong Qu , Tao Lu , Jingqing Hu
{"title":"花肝解毒汤（HGJDD）通过FOXO4/ERK/HNF4α信号通路对乙型肝炎病毒（HBV）的抗病毒活性","authors":"Hongxuan Tong , Jiale Zhang , Lijie Jiang , Rendong Qu , Tao Lu , Jingqing Hu","doi":"10.1016/j.jep.2024.119238","DOIUrl":null,"url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Chronic hepatitis B virus (HBV) infection is still a widespread global health issue. HuaganJiedu Decoction (HGJDD) is a common prescription for treating HBV in China, which has the effect of enhancing antiviral efficacy and improving clinical efficacy. However, its precise mechanism of action remains unclear, warranting further investigation to elucidate its therapeutic potential and integration into standard medical practices.</div></div><div><h3>Aim of the study</h3><div>This study aims to explore the therapeutic mechanism of HuaganJiedu Decoction (HGJDD) in HBV.</div></div><div><h3>Materials and methods</h3><div>We investigated the therapeutic potential of HGJDD, and LC-MS analysis characterized the chemical profile of HGJDD. In vitro, we utilized HepG2.2.15 cell line to assess cytotoxicity and treatment efficacy of HGJDD compared to Entecavir controls. In vivo, assessments included monitoring HBV-related biomarkers and viral load. Network pharmacology and RNA-seq analyses identified molecular pathways and targets influenced by HGJDD treatment. Immunofluorescence and Western blotting provided further insights into the therapeutic mechanisms underlying HGJDD for HBV.</div></div><div><h3>Results</h3><div>HGJDD showed no toxicity on HepG2.2.15 cells at 10%, 20%, 40%, and 80% serum concentrations. In vitro, HGJDD reduced HBsAg, HBeAg, and HBV DNA levels by dose-dependently and time-dependently. HGJDD can decrease the levels of HBsAg, HBeAg, and HBV DNA in serum and liver levels, meanwhile the therapeutic effect of high-dose HGJDD approach to EVT’s in HBV Tg mice. According to intersection of network pharmacology and transcriptome, FOXO signal pathway was highlighted as potential targets and Immunofluorescence find that FOXO4D protein expression lever was increased in three HGJDD group, especially in high-dose HGJDD group. Western blotting confirmed increased level of FOXO4, ERK, and p-ERK and decreased levels of HNF4α, which reflected that the therapeutic effect was closely to FOXO4/ERK/HNF4α signal pathway.</div></div><div><h3>Conclusions</h3><div>Traditional Chinese medicine (TCM) offers diverse herbal treatments for HBV, with HGJDD showing efficacy in reducing HBsAg, HBeAg, and HBV DNA levels at cellular and animal levels. This study identified that FOXO4/ERK/HNF4α signal pathway played an important role in HGJDD’s therapeutic effects. These findings support HGJDD’s potential in HBV treatment, providing a scientific basis for clinical use.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 119238"},"PeriodicalIF":4.8000,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Antiviral activity of HuaganJiedu decoction (HGJDD) against hepatitis B virus (HBV) through FOXO4/ERK/HNF4α signal pathway\",\"authors\":\"Hongxuan Tong , Jiale Zhang , Lijie Jiang , Rendong Qu , Tao Lu , Jingqing Hu\",\"doi\":\"10.1016/j.jep.2024.119238\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Ethnopharmacological relevance</h3><div>Chronic hepatitis B virus (HBV) infection is still a widespread global health issue. HuaganJiedu Decoction (HGJDD) is a common prescription for treating HBV in China, which has the effect of enhancing antiviral efficacy and improving clinical efficacy. However, its precise mechanism of action remains unclear, warranting further investigation to elucidate its therapeutic potential and integration into standard medical practices.</div></div><div><h3>Aim of the study</h3><div>This study aims to explore the therapeutic mechanism of HuaganJiedu Decoction (HGJDD) in HBV.</div></div><div><h3>Materials and methods</h3><div>We investigated the therapeutic potential of HGJDD, and LC-MS analysis characterized the chemical profile of HGJDD. In vitro, we utilized HepG2.2.15 cell line to assess cytotoxicity and treatment efficacy of HGJDD compared to Entecavir controls. In vivo, assessments included monitoring HBV-related biomarkers and viral load. Network pharmacology and RNA-seq analyses identified molecular pathways and targets influenced by HGJDD treatment. Immunofluorescence and Western blotting provided further insights into the therapeutic mechanisms underlying HGJDD for HBV.</div></div><div><h3>Results</h3><div>HGJDD showed no toxicity on HepG2.2.15 cells at 10%, 20%, 40%, and 80% serum concentrations. In vitro, HGJDD reduced HBsAg, HBeAg, and HBV DNA levels by dose-dependently and time-dependently. HGJDD can decrease the levels of HBsAg, HBeAg, and HBV DNA in serum and liver levels, meanwhile the therapeutic effect of high-dose HGJDD approach to EVT’s in HBV Tg mice. According to intersection of network pharmacology and transcriptome, FOXO signal pathway was highlighted as potential targets and Immunofluorescence find that FOXO4D protein expression lever was increased in three HGJDD group, especially in high-dose HGJDD group. Western blotting confirmed increased level of FOXO4, ERK, and p-ERK and decreased levels of HNF4α, which reflected that the therapeutic effect was closely to FOXO4/ERK/HNF4α signal pathway.</div></div><div><h3>Conclusions</h3><div>Traditional Chinese medicine (TCM) offers diverse herbal treatments for HBV, with HGJDD showing efficacy in reducing HBsAg, HBeAg, and HBV DNA levels at cellular and animal levels. This study identified that FOXO4/ERK/HNF4α signal pathway played an important role in HGJDD’s therapeutic effects. These findings support HGJDD’s potential in HBV treatment, providing a scientific basis for clinical use.</div></div>\",\"PeriodicalId\":15761,\"journal\":{\"name\":\"Journal of ethnopharmacology\",\"volume\":\"340 \",\"pages\":\"Article 119238\"},\"PeriodicalIF\":4.8000,\"publicationDate\":\"2025-01-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of ethnopharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S037887412401537X\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of ethnopharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S037887412401537X","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Antiviral activity of HuaganJiedu decoction (HGJDD) against hepatitis B virus (HBV) through FOXO4/ERK/HNF4α signal pathway
Ethnopharmacological relevance
Chronic hepatitis B virus (HBV) infection is still a widespread global health issue. HuaganJiedu Decoction (HGJDD) is a common prescription for treating HBV in China, which has the effect of enhancing antiviral efficacy and improving clinical efficacy. However, its precise mechanism of action remains unclear, warranting further investigation to elucidate its therapeutic potential and integration into standard medical practices.
Aim of the study
This study aims to explore the therapeutic mechanism of HuaganJiedu Decoction (HGJDD) in HBV.
Materials and methods
We investigated the therapeutic potential of HGJDD, and LC-MS analysis characterized the chemical profile of HGJDD. In vitro, we utilized HepG2.2.15 cell line to assess cytotoxicity and treatment efficacy of HGJDD compared to Entecavir controls. In vivo, assessments included monitoring HBV-related biomarkers and viral load. Network pharmacology and RNA-seq analyses identified molecular pathways and targets influenced by HGJDD treatment. Immunofluorescence and Western blotting provided further insights into the therapeutic mechanisms underlying HGJDD for HBV.
Results
HGJDD showed no toxicity on HepG2.2.15 cells at 10%, 20%, 40%, and 80% serum concentrations. In vitro, HGJDD reduced HBsAg, HBeAg, and HBV DNA levels by dose-dependently and time-dependently. HGJDD can decrease the levels of HBsAg, HBeAg, and HBV DNA in serum and liver levels, meanwhile the therapeutic effect of high-dose HGJDD approach to EVT’s in HBV Tg mice. According to intersection of network pharmacology and transcriptome, FOXO signal pathway was highlighted as potential targets and Immunofluorescence find that FOXO4D protein expression lever was increased in three HGJDD group, especially in high-dose HGJDD group. Western blotting confirmed increased level of FOXO4, ERK, and p-ERK and decreased levels of HNF4α, which reflected that the therapeutic effect was closely to FOXO4/ERK/HNF4α signal pathway.
Conclusions
Traditional Chinese medicine (TCM) offers diverse herbal treatments for HBV, with HGJDD showing efficacy in reducing HBsAg, HBeAg, and HBV DNA levels at cellular and animal levels. This study identified that FOXO4/ERK/HNF4α signal pathway played an important role in HGJDD’s therapeutic effects. These findings support HGJDD’s potential in HBV treatment, providing a scientific basis for clinical use.
期刊介绍：
The Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people''s use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.
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