{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T12:30:26Z","timestamp":1763037026017,"version":"build-2065373602"},"reference-count":64,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2016,11,23]],"date-time":"2016-11-23T00:00:00Z","timestamp":1479859200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Hepatic fibrosis is a naturally occurring wound-healing reaction, with an imbalance of extracellular matrix (ECM) during tissue repair response, which can further deteriorate to hepatocellular carcinoma without timely treatment. Inhibiting activated hepatic stellate cell (HSC) proliferation and inducing apoptosis are the main methods for the treatment of liver fibrosis. In our previous study, we found that the TOA-glycine derivative (G-TOA) had exhibited more significant inhibitory activity against HepG2 cells and better hydrophilicity than TOA, ligustrazine (TMP), and oleanolic acid (OA). However, inhibiting activated HSC proliferation and inducing apoptosis by G-TOA had not been reported. In this paper, the selective cytotoxicity of G-TOA was evaluated on HSC-T6 cells and L02 cells, and apoptosis mechanisms were explored. It was found that G-TOA could selectively inhibit the proliferation of activated HSC-T6 cells, induce morphological changes, early apoptosis, and mitochondrial membrane potential depolarization, increase intracellular free calcium levels, downregulate the expression of NF-\u03baB\/p65 and COX-2 protein, and decrease the ratio of Bcl-2\/Bax, thereby inducing HSC-T6 cell apoptosis. Thence, G-TOA might be a potential antifibrosis agent for the therapy of hepatic fibrosis, provided that it exerts anti-fibrosis effects on activated HSC-T6 cells.<\/jats:p>","DOI":"10.3390\/molecules21111599","type":"journal-article","created":{"date-parts":[[2016,11,23]],"date-time":"2016-11-23T11:12:14Z","timestamp":1479899534000},"page":"1599","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Ligustrazine-Oleanolic Acid Glycine Derivative, G-TOA, Selectively Inhibited the Proliferation and Induced Apoptosis of Activated HSC-T6 Cells"],"prefix":"10.3390","volume":"21","author":[{"given":"Siling","family":"Bi","sequence":"first","affiliation":[{"name":"Department of Pathology, Beijing University of Chinese Medicine, Beijing 100102, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5725-6435","authenticated-orcid":false,"given":"Fuhao","family":"Chu","sequence":"additional","affiliation":[{"name":"School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mina","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Beijing University of Chinese Medicine, Beijing 100102, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bi","family":"Li","sequence":"additional","affiliation":[{"name":"School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pei","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Pathology, Beijing University of Chinese Medicine, Beijing 100102, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huazheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Beijing University of Chinese Medicine, Beijing 100102, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Penglong","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenbo","family":"Guo","sequence":"additional","affiliation":[{"name":"School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang","family":"Xu","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Shandong University of Chinese Medicine, Jinan 250001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liwei","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Pathology, Beijing University of Chinese Medicine, Beijing 100102, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6765-9545","authenticated-orcid":false,"given":"Haimin","family":"Lei","sequence":"additional","affiliation":[{"name":"School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuzhong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Beijing University of Chinese Medicine, Beijing 100102, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2016,11,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1007\/s005350070045","article-title":"Hepatic stellate cells: A target for the treatment of liver fibrosis","volume":"35","author":"Wu","year":"2000","journal-title":"J. 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