{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:13:24Z","timestamp":1785413604655,"version":"3.56.0"},"reference-count":43,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"publisher","award":["2022YFD2200604-04"],"award-info":[{"award-number":["2022YFD2200604-04"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82060700"],"award-info":[{"award-number":["82060700"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82060700"],"award-info":[{"award-number":["82060700"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Melia azedarach L. is a plant known for its traditional medicinal uses. Limonoids (triterpenes), which have a wide range of pharmacological effects, are the most critical active ingredients; however, their potential effects on liver cancer remain to be further explored. In this study, seven limonoids were isolated from the bark of Melia azedarach, including two new compounds, 11\u03b1-hydroxy-12-Oxo-Meliarachin I (1) and 29-Oxo-12-dehydroneoazedarachin D (3), along with five known compounds (2, 4\u20137), to evaluate their effect on liver cancer in vitro. The results showed that compounds 1\u20137 exhibited varying degrees of inhibitory effects on Hep3B cells. Among these, compound 6, Isotoosendanin (ITSN), displayed the most potent activity, with an IC50 value of 15.06 \u03bcg\/mL. Mechanism studies have shown that ITSN inhibits cell proliferation and promotes apoptosis in Hep3B cells. It induces reactive oxygen species (ROS) accumulation to trigger oxidative stress injury, suppresses the activation of the MAPK and PI3K\/AKT signaling pathways, further activates the p53 pathway to induce cell cycle arrest, and ultimately initiates the apoptotic cascade. ITSN can also inhibit tumor growth in immunodeficient mice receiving allogeneic transplantation. In summary, we systematically studied the limonoids in the bark of Melia azedarach and elucidated the anti-hepatocarcinoma activity of ITSN in vitro and in vivo, providing promising evidence for its potential use as a natural active ingredient in the prevention and treatment of cancer.<\/jats:p>","DOI":"10.3390\/antiox15050562","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T12:31:56Z","timestamp":1777465916000},"page":"562","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Anti-Hepatocarcinoma Activity and Mechanism of Isosendanin and Its Novel Structural Analogues Isolated from the Bark of Melia azedarach L.: In Vitro and In Vivo Studies"],"prefix":"10.3390","volume":"15","author":[{"given":"Yuanyuan","family":"Huang","sequence":"first","affiliation":[{"name":"Institute of Advanced Carbon Conversion Technology, Huaqiao University, Xiamen 361021, China"},{"name":"Fujian Provincial Key Laboratory of Biomass Low-Carbon Conversion, Huaqiao University, Xiamen 361021, China"},{"name":"College of Chemical Engineering, Huaqiao University, Xiamen 361021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erjian","family":"Gao","sequence":"additional","affiliation":[{"name":"Institute of Advanced Carbon Conversion Technology, Huaqiao University, Xiamen 361021, China"},{"name":"Fujian Provincial Key Laboratory of Biomass Low-Carbon Conversion, Huaqiao University, Xiamen 361021, China"},{"name":"College of Chemical Engineering, Huaqiao University, Xiamen 361021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Traditional Chinese and Zhuang-Yao Ethnic Medicine, Guangxi University of Chinese Medicine, Nanning 530200, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingquan","family":"Yuan","sequence":"additional","affiliation":[{"name":"Institute of Traditional Chinese and Zhuang-Yao Ethnic Medicine, Guangxi University of Chinese Medicine, Nanning 530200, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8477-9370","authenticated-orcid":false,"given":"Yanchun","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Traditional Chinese and Zhuang-Yao Ethnic Medicine, Guangxi University of Chinese Medicine, Nanning 530200, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Advanced Carbon Conversion Technology, Huaqiao University, Xiamen 361021, China"},{"name":"Fujian Provincial Key Laboratory of Biomass Low-Carbon Conversion, Huaqiao University, Xiamen 361021, China"},{"name":"College of Chemical Engineering, Huaqiao University, Xiamen 361021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5115-8260","authenticated-orcid":false,"given":"Xiaoping","family":"Rao","sequence":"additional","affiliation":[{"name":"Institute of Advanced Carbon Conversion Technology, Huaqiao University, Xiamen 361021, China"},{"name":"Fujian Provincial Key Laboratory of Biomass Low-Carbon Conversion, Huaqiao University, Xiamen 361021, China"},{"name":"College of Chemical Engineering, Huaqiao University, Xiamen 361021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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