{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T14:59:12Z","timestamp":1792162752162,"version":"4.4.0"},"reference-count":47,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T00:00:00Z","timestamp":1747267200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Endoplasmic reticulum stress (ERS) contributes to hepatocyte inflammation, triggered by prolonged exposure to lipotoxicity, and promotes non-alcoholic fatty liver disease (NAFLD) progression by recruiting and activating hepatic macrophages, which accelerate fibrosis and exacerbate disease progression. Here, we aimed to evaluate the therapeutic potential of ginsenoside Rh2 (Rh2) in a cell model of NAFLD induced by the ERS inducer thapsigargin (THA). Methods: HepG2 cells were treated with THA to induce ERS and mimic NAFLD conditions. The effects of Rh2 on ERS, lipid accumulation, and apoptosis were assessed in HepG2 cells. Additionally, THP-1 cells were used to investigate macrophage activation upon exposure to conditioned medium (CM) from THA- and Rh2-treated HepG2 cells. Gene and protein expression of inflammatory and lipid synthesis markers were analyzed, as well as M1\/M2 macrophage polarization markers. Results: Rh2 inhibited THA-induced apoptosis, ERS, and lipid accumulation in HepG2 cells. It also reduced the expression of lipid synthesis genes (SREBF1, FAS) and inflammatory markers (IL-6, IL-1\u03b2, TNF-\u03b1, MCP-1). CM from Rh2-treated HepG2 cells suppressed macrophage activation in THP-1 cells, decreased M1 polarization markers (CD80, CD86), and increased M2 markers (CD163, Arg1, MRC-1). Conclusions: These results suggest that Rh2 effectively suppresses inflammation and lipid storage in ERS-induced HepG2 cells while modulating the crosstalk between hepatocytes and macrophages. These findings underscore the potential of Rh2 as a promising therapeutic agent for the prevention and early intervention of NAFLD progression.<\/jats:p>","DOI":"10.3390\/nu17101682","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T06:10:44Z","timestamp":1747289444000},"page":"1682","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Ginsenoside Rh2 Mitigates Endoplasmic Reticulum Stress-Induced Apoptosis and Inflammation and Through Inhibition of Hepatocyte\u2013Macrophage Inflammatory Crosstalk"],"prefix":"10.3390","volume":"17","author":[{"given":"Shinjung","family":"Park","sequence":"first","affiliation":[{"name":"Division of Food and Nutrition, Chonnam National University, Gwangju 61186, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1239-0611","authenticated-orcid":false,"given":"Inae","family":"Jeong","sequence":"additional","affiliation":[{"name":"Division of Food and Nutrition, Chonnam National University, Gwangju 61186, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8338-2571","authenticated-orcid":false,"given":"Ok-Kyung","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Food and Nutrition, Chonnam National University, Gwangju 61186, Republic of Korea"},{"name":"Human Ecology Research Institute, Chonnam National University, Gwangju 61186, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"103043","DOI":"10.1016\/j.arcmed.2024.103043","article-title":"Global Prevalence of Nonalcoholic Fatty Liver Disease: An Updated Review Meta-Analysis comprising a Population of 78 million from 38 Countries","volume":"55","author":"Letafatkar","year":"2024","journal-title":"Arch. 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