{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T20:03:46Z","timestamp":1789243426299,"version":"build-2803163510"},"reference-count":39,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T00:00:00Z","timestamp":1720137600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Thailand Science Research and Innovation, and Naresuan University","award":["R2567B041"],"award-info":[{"award-number":["R2567B041"]}]},{"name":"Thailand Science Research and Innovation, and Naresuan University","award":["R2566A056"],"award-info":[{"award-number":["R2566A056"]}]},{"name":"Reinventing University Program 2023, The Ministry of Higher Education, Science, Research and Innovation (MHESI)","award":["R2567B041"],"award-info":[{"award-number":["R2567B041"]}]},{"name":"Reinventing University Program 2023, The Ministry of Higher Education, Science, Research and Innovation (MHESI)","award":["R2566A056"],"award-info":[{"award-number":["R2566A056"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Liver fibrosis, a consequence of chronic liver damage or inflammation, is characterized by the excessive buildup of extracellular matrix components. This progressive condition significantly raises the risk of severe liver diseases like cirrhosis and hepatocellular carcinoma. The lack of approved therapeutics underscores the urgent need for novel anti-fibrotic drugs. Hepatic stellate cells (HSCs), key players in fibrogenesis, are promising targets for drug discovery. This study investigated the anti-fibrotic potential of Citrus hystrix DC. (KL) and its bioactive compound, \u03b2-citronellol (\u03b2-CIT), in a human HSC cell line (LX-2). Cells exposed to TGF-\u03b21 to induce fibrogenesis were co-treated with crude KL extract and \u03b2-CIT. Gene expression was analyzed by real-time qRT-PCR to assess fibrosis-associated genes (ACTA2, COL1A1, TIMP1, SMAD2). The release of matrix metalloproteinase 9 (MMP-9) was measured by ELISA. Proteomic analysis and molecular docking identified potential signaling proteins and modeled protein\u2013ligand interactions. The results showed that both crude KL extract and \u03b2-CIT suppressed HSC activation genes and MMP-9 levels. The MAPK signaling pathway emerged as a potential target of \u03b2-CIT. This study demonstrates the ability of KL extract and \u03b2-CIT to inhibit HSC activation during TGF-\u03b21-induced fibrogenesis, suggesting a promising role of \u03b2-CIT in anti-hepatic fibrosis therapies.<\/jats:p>","DOI":"10.3390\/biom14070800","type":"journal-article","created":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T14:40:50Z","timestamp":1720449650000},"page":"800","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Investigating the Antifibrotic Effects of \u03b2-Citronellol on a TGF-\u03b21-Stimulated LX-2 Hepatic Stellate Cell Model"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0735-1941","authenticated-orcid":false,"given":"Watunyoo","family":"Buakaew","sequence":"first","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Srinakharinwirot University, Bangkok 10110, Thailand"},{"name":"Cellular and Molecular Immunology Research Unit (CMIRU), Faculty of Allied Health Sciences, Naresuan University, Phitsanulok 65000, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4428-4140","authenticated-orcid":false,"given":"Sucheewin","family":"Krobthong","sequence":"additional","affiliation":[{"name":"Center of Excellence in Natural Products Chemistry (CENP), Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency (NSTDA), Pathum Thani 12120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0701-4205","authenticated-orcid":false,"given":"Yodying","family":"Yingchutrakul","sequence":"additional","affiliation":[{"name":"National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency (NSTDA), Pathum Thani 12120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pachuen","family":"Potup","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Immunology Research Unit (CMIRU), Faculty of Allied Health Sciences, Naresuan University, Phitsanulok 65000, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6771-4970","authenticated-orcid":false,"given":"Yordhathai","family":"Thongsri","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Immunology Research Unit (CMIRU), Faculty of Allied Health Sciences, Naresuan University, Phitsanulok 65000, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2397-8381","authenticated-orcid":false,"given":"Krai","family":"Daowtak","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Immunology Research Unit (CMIRU), Faculty of Allied Health Sciences, Naresuan University, Phitsanulok 65000, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2581-6407","authenticated-orcid":false,"given":"Antonio","family":"Ferrante","sequence":"additional","affiliation":[{"name":"Department of Immunopathology, South Australia (SA) Pathology, Women\u2019s and Children\u2019s Hospital, Adelaide, SA 5006, Australia"},{"name":"The Adelaide Medical School, The School of Biological Science and the Robinson Research Institute, University of Adelaide, Adelaide, SA 5000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4039-5882","authenticated-orcid":false,"given":"Kanchana","family":"Usuwanthim","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Immunology Research Unit (CMIRU), Faculty of Allied Health Sciences, Naresuan University, Phitsanulok 65000, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.jhep.2023.03.017","article-title":"Global burden of liver disease: 2023 update","volume":"79","author":"Devarbhavi","year":"2023","journal-title":"J. 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