{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T02:00:08Z","timestamp":1767924008056,"version":"3.49.0"},"reference-count":35,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2017,3,6]],"date-time":"2017-03-06T00:00:00Z","timestamp":1488758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>A novel hepatoprotective oleanolic acid derivative, 3-oxours-oleana-9(11), 12-dien-28-oic acid (Oxy-Di-OA), has been reported. In previous studies, we found that Oxy-Di-OA presented the anti-HBV (Hepatitis B Virus) activity (IC50 = 3.13 \u00b5g\/mL). Remarkably, it is superior to lamivudine in the inhibition of the rebound of the viral replication rate. Furthermore, Oxy-Di-OA showed good performance of anti-HBV activity in vivo. Some studies showed that liver fibrosis may affiliate with HBV gene mutations. In addition, the anti-hepatic fibrosis activity of Oxy-Di-OA has not been studied. Therefore, we evaluated the protective effect of Oxy-Di-OA against carbon tetrachloride (CCl4)-induced liver injury in rats. Daily intraperitoneally administration of Oxy-Di-OA prevented the development of CCl4-induced liver fibrosis, which was evidenced by histological study and immunohistochemical analysis. The entire experimental protocol lasted nine weeks. Oxy-Di-OA significantly suppressed the increases of plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels (p &lt; 0.05). Furthermore, Oxy-Di-OA could prevent expression of transforming growth factor \u03b21 (TGF-\u03b21). It is worth noting that the high-dose group Oxy-Di-OA is superior to bifendate in elevating hepatic function. Compared to the model group, Oxy-Di-OA in the high-dose group and low-dose group can significantly reduce the liver and spleen indices (p &lt; 0.05). The acute toxicity test showed that LD50 and a 95% confidence interval (CIs) value of Oxy-Di-OA were 714.83 mg\/kg and 639.73\u2013798.73 mg\/kg via intraperitoneal injection in mice, respectively. The LD50 value of Oxy-Di-OA exceeded 2000 mg\/kg via gavage in mice. In addition, a simple and rapid high performance liquid chromatography-ultraviolet (HPLC-UV) method was developed and validated to study the pharmacokinetic characteristics of the compound. After single-dose oral administration, time to reach peak concentration of Oxy-Di-OA (Cmax = 8.18 \u00b1 0.66 \u03bcg\/mL) was 10 \u00b1 2.19 h; the elimination half-life and area under the concentration-time curve from t = 0 to the last time of Oxy-Di-OA was 2.19 h and 90.21 \u03bcg\u00b7h\/mL, respectively.<\/jats:p>","DOI":"10.3390\/ijms18030553","type":"journal-article","created":{"date-parts":[[2017,3,9]],"date-time":"2017-03-09T06:56:43Z","timestamp":1489042603000},"page":"553","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["A New Oleanolic Acid Derivative against CCl4-Induced Hepatic Fibrosis in Rats"],"prefix":"10.3390","volume":"18","author":[{"given":"Hongjun","family":"Xiang","sequence":"first","affiliation":[{"name":"School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaotian","family":"Han","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"}]},{"given":"Wenqiang","family":"Yan","sequence":"additional","affiliation":[{"name":"School of Chinese Pharmacy, 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":"Bing","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Chinese Pharmacy, 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":"Tianxin","family":"Xie","sequence":"additional","affiliation":[{"name":"School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Menglu","family":"Jia","sequence":"additional","affiliation":[{"name":"School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengmeng","family":"Yan","sequence":"additional","affiliation":[{"name":"School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Chinese Pharmacy, 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":"Penglong","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Chinese Pharmacy, 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"}]}],"member":"1968","published-online":{"date-parts":[[2017,3,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1146\/annurev-pathol-011110-130246","article-title":"Pathogenesis of liver fibrosis","volume":"6","author":"Friedman","year":"2011","journal-title":"Annu. 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