{"title":"20(S)-Ginsenoside Rg3 Partially Induces Maturation of HepG2 Cells via the AMPK/HNF4A Pathway.","authors":"Li Zheng, Yiheng Ding, Xinhao Li, Jingxuan Jia, Yanning Li, Jinsheng Qi","doi":"10.18502/ijph.v54i6.18904","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>We aimed to investigate whether 20(S)-ginsenoside Rg3 (Rg3) reduced heterogeneity by inducing the maturation of HepG2 cells via the AMP-activated protein kinase (AMPK)/hepatocyte nuclear factor 4A (HNF4A) pathway.</p><p><strong>Methods: </strong>This in vitro cell research study was conducted under the guidance of Hebei Medical University, Hebei, China, from Sep 2022 to Dec 2023. HepG2 cells were treated with varying concentrations of Rg3 in a low glucose microenvironment. The mRNA expression of <i>ALBUMIN</i> (<i>ALB</i>, a marker for hepatocyte function) and <i>HNF4A</i> (a marker for differentiation of HCC cell), and AMPK protein levels were measured after significant changes in cell morphology were observed. Additionally, 5-Aminoimidazole-4-carboxamide1-β-D-ribofuranoside (AICAR) (an AMPK agonist) and Compound C (an AMPK inhibitor) were used to explore further the underlying mechanism.</p><p><strong>Results: </strong>Under treatment of 5 μM, 10 μM, and 20 μM Rg3, some cells became flattened and larger, and there was an increase in the mRNA expression of <i>ALB</i> and <i>HNF4A</i> (<i>P</i><0.05). However, there was a decreasing trend in AMPK protein content with 8 μM Rg3 (<i>P</i><0.05). Compared to the control group, some cells exposed to 8 μM Rg3 exhibited pronounced morphological changes, along with upregulated expression of <i>ALB</i> and <i>HNF4A</i> mRNA. However, no such changes were observed when 8 μM Rg3 was combined with 1.6 mM AICAR. Compared to the control group, 10 μM Compound C or 8 μM Rg3 treatments led to similar changes in cell morphology and showed an increasing trend in <i>HNF4A</i> mRNA expression. Additionally, after treatment with Compound C, pHNF4A was mainly in the nucleus, while after Rg3 treatment, it was mostly in the cytoplasm.</p><p><strong>Conclusion: </strong>Rg3 partially induced the maturation of HepG2 cells through the AMPK/HNF4A pathway.</p>","PeriodicalId":49173,"journal":{"name":"Iranian Journal of Public Health","volume":"54 6","pages":"1263-1271"},"PeriodicalIF":1.6000,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12241739/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Iranian Journal of Public Health","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.18502/ijph.v54i6.18904","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH","Score":null,"Total":0}
引用次数: 0
Abstract
Background: We aimed to investigate whether 20(S)-ginsenoside Rg3 (Rg3) reduced heterogeneity by inducing the maturation of HepG2 cells via the AMP-activated protein kinase (AMPK)/hepatocyte nuclear factor 4A (HNF4A) pathway.
Methods: This in vitro cell research study was conducted under the guidance of Hebei Medical University, Hebei, China, from Sep 2022 to Dec 2023. HepG2 cells were treated with varying concentrations of Rg3 in a low glucose microenvironment. The mRNA expression of ALBUMIN (ALB, a marker for hepatocyte function) and HNF4A (a marker for differentiation of HCC cell), and AMPK protein levels were measured after significant changes in cell morphology were observed. Additionally, 5-Aminoimidazole-4-carboxamide1-β-D-ribofuranoside (AICAR) (an AMPK agonist) and Compound C (an AMPK inhibitor) were used to explore further the underlying mechanism.
Results: Under treatment of 5 μM, 10 μM, and 20 μM Rg3, some cells became flattened and larger, and there was an increase in the mRNA expression of ALB and HNF4A (P<0.05). However, there was a decreasing trend in AMPK protein content with 8 μM Rg3 (P<0.05). Compared to the control group, some cells exposed to 8 μM Rg3 exhibited pronounced morphological changes, along with upregulated expression of ALB and HNF4A mRNA. However, no such changes were observed when 8 μM Rg3 was combined with 1.6 mM AICAR. Compared to the control group, 10 μM Compound C or 8 μM Rg3 treatments led to similar changes in cell morphology and showed an increasing trend in HNF4A mRNA expression. Additionally, after treatment with Compound C, pHNF4A was mainly in the nucleus, while after Rg3 treatment, it was mostly in the cytoplasm.
Conclusion: Rg3 partially induced the maturation of HepG2 cells through the AMPK/HNF4A pathway.
期刊介绍：
Iranian Journal of Public Health has been continuously published since 1971, as the only Journal in all health domains, with wide distribution (including WHO in Geneva and Cairo) in two languages (English and Persian). From 2001 issue, the Journal is published only in English language. During the last 41 years more than 2000 scientific research papers, results of health activities, surveys and services, have been published in this Journal. To meet the increasing demand of respected researchers, as of January 2012, the Journal is published monthly. I wish this will assist to promote the level of global knowledge. The main topics that the Journal would welcome are: Bioethics, Disaster and Health, Entomology, Epidemiology, Health and Environment, Health Economics, Health Services, Immunology, Medical Genetics, Mental Health, Microbiology, Nutrition and Food Safety, Occupational Health, Oral Health. We would be very delighted to receive your Original papers, Review Articles, Short communications, Case reports and Scientific Letters to the Editor on the above mentioned research areas.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
