{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T21:36:15Z","timestamp":1778276175899,"version":"3.51.4"},"reference-count":26,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T00:00:00Z","timestamp":1717977600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Lanzhou University First Hospital","award":["ldyyyn2020-02"],"award-info":[{"award-number":["ldyyyn2020-02"]}]},{"name":"Lanzhou University First Hospital","award":["ldyyyn2020-14"],"award-info":[{"award-number":["ldyyyn2020-14"]}]},{"name":"Gansu Clinical Medical Research Center","award":["21JR7RA392"],"award-info":[{"award-number":["21JR7RA392"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Objective<\/jats:title>\n<jats:p>The present study aims to investigate the specific protective effects and underlying mechanisms of Ganshuang granule (GSG) on dimethylnitrosamine (DMN)-induced hepatic fibrosis in rat models.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Hepatic fibrosis was experimentally evoked in rats by DMN administration, and varying dosages of GSG were employed as an intervention. Hepatocellular damage was assessed by measuring serum levels of aminotransferase and bilirubin, accompanied by histopathological examinations of hepatic tissue. The hepatic concentrations of platelet-derived growth factor (PDGF) and transforming growth factor-\u03b21 (TGF-\u03b21) were quantitated via enzyme-linked immunosorbent assay (ELISA). The expression of \u03b1-smooth muscle actin (\u03b1-SMA) within hepatic tissue was evaluated using immunohistochemical techniques. The levels of hepatic interferon-\u03b3 (IFN-\u03b3), tumor necrosis factor-\u03b1 (TNF-\u03b1), and a spectrum of interleukins (IL-2, IL-4, IL-6, IL-10) were quantified by quantitative real-time PCR (qRT-PCR). Additionally, hepatic stellate cells (HSCs) were cultured <jats:italic>in vitro<\/jats:italic> and exposed to TNF-\u03b1 in the presence of naringin, a principal component of GSG. The gene expression levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) and matrix metallopeptidase-1 (MMP-1) in these cells were also quantified by qRT-PCR. Proliferative activity of HSCs was evaluated by the Cell Counting Kit-8 assay. Finally, alterations in Smad protein expression were analyzed through Western blotting.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Administration of GSG in rats with fibrosis resulted in reduced levels of serum aminotransferases and bilirubin, along with alleviation of histopathological liver injury. Furthermore, the fibrosis rats treated with GSG exhibited significant downregulation of hepatic TGF-\u03b21, PDGF, and TNF-\u03b1 levels. Additionally, GSG treatment led to increased mRNA levels of IFN-\u03b3, IL-2, and IL-4, as well as decreased expression of \u03b1-SMA in the liver. Furthermore, treatment with naringin, a pivotal extract of GSG, resulted in elevated expression of MMP-1 and decreased levels of TIMP-1 in TNF-\u03b1-stimulated HSCs when compared to the control group. Additionally, naringin administration led to a reduction in Smad expression within the HSCs.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>GSG has the potential to mitigate fibrosis induced by DMN in rat models through the regulation of inflammatory and fibrosis factors. Notably, naringin, the primary extract of GSG, may exert a pivotal role in modulating the TGF-\u03b2-Smad signaling pathway.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0304185","type":"journal-article","created":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T17:33:51Z","timestamp":1718040831000},"page":"e0304185","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Naringin from Ganshuang granule inhibits inflammatory to relieve liver fibrosis through TGF-\u03b2-Smad signaling pathway"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8043-2158","authenticated-orcid":true,"given":"Fuchun","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Gan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaorong","family":"Mao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongping","family":"Duan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junfeng","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,6,10]]},"reference":[{"issue":"3","key":"pone.0304185.ref001","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/s41575-020-00372-7","article-title":"Molecular and cellular mechanisms of liver fibrosis and its regression","volume":"18","author":"T Kisseleva","year":"2021","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"5","key":"pone.0304185.ref002","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1136\/gutjnl-2019-318372","article-title":"Rilpivirine attenuates liver fibrosis through selective STAT1-mediated apoptosis in hepatic stellate cells","volume":"69","author":"A Mart\u00ed-Rodrigo","year":"2020","journal-title":"Gut"},{"issue":"4","key":"pone.0304185.ref003","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1002\/hep.30590","article-title":"NGM282 Improves Liver Fibrosis and Histology in 12 Weeks in Patients With Nonalcoholic Steatohepatitis","volume":"71","author":"S Harrison","year":"2020","journal-title":"Hepatology"},{"issue":"1","key":"pone.0304185.ref004","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.jhep.2014.03.009","article-title":"Traditional Chinese Medicine (TCM) for fibrotic liver disease: hope and hype","volume":"61","author":"L Zhang","year":"2014","journal-title":"J Hepatol"},{"issue":"41","key":"pone.0304185.ref005","doi-asserted-by":"crossref","first-page":"e22692","DOI":"10.1097\/MD.0000000000022692","article-title":"Clinical efficacy and safety of Ganshuang granules as an adjuvant treatment for chronic hepatitis B liver fibrosis: A protocol for systematic review and meta analysis","volume":"99","author":"S Zeng","year":"2020","journal-title":"Medicine"},{"issue":"11","key":"pone.0304185.ref006","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.3390\/cells8111419","article-title":"TGF-\u03b2 in Hepatic Stellate Cell Activation and Liver Fibrogenesis-Updated 2019","volume":"8","author":"B Dewidar","year":"2019","journal-title":"Cells"},{"key":"pone.0304185.ref007","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.matbio.2017.11.011","article-title":"Matrix metalloproteinase functions in hepatic injury and fibrosis","author":"M. 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