{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T03:20:44Z","timestamp":1762658444376,"version":"build-2065373602"},"reference-count":41,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2019,8,22]],"date-time":"2019-08-22T00:00:00Z","timestamp":1566432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Leaf extract of Nelumbo nucifera (NLE) has been demonstrated to possess anti-atherosclerosis, improve alcohol-induced steatohepatitis, prevent high-fat diet-induced obesity, and inhibit the proliferation and metastasis of human breast cancer cells. This study determines the chemopreventive role of NLE against 2-acetylaminofluorene (AAF)-induced hepatocellular carcinoma (HCC) in rats. AAF was used to induce hepatocarcinogenesis in rats through genetic and nongenetic effects. After administration for 12 weeks, NLE (0.5\u20132%) supplementation orally inhibited AAF (0.03%)-induced hepatic fibrosis which appears during the development of premalignant lesions in rats. After the 6-month experiment, NLE supplementation resulted in decreasing AAF-induced serum parameters of hepatic injury, including the level of triglycerides, total cholesterol, alpha-fetoprotein (AFP), and inflammatory mediator interleukin (IL)-6 and tumor necrosis factor (TNF)-\u03b1 as well as the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (\u03b3GT). NLE supplementation also reduced AAF-induced lipid peroxidation and 8-hydroxy-2\u2032-deoxyguanosine (8-OHdG) formation in the rat liver. Hepatic histopathological investigation revealed that NLE supplementation attenuated the AAF-induced HCC and glutathione S-transferase-Pi (GST-Pi) expression. Furthermore, NLE supplementation increased the expression of transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream targets, including catalase, glutathion peroxidase (GPx), and superoxide dismutase 1 (SOD-1) in the rat liver. Our findings indicate that NLE supplementation inhibited AAF-induced hepatocarcinogenesis by enhancing antioxidative potential and alleviating inflammation in rats.<\/jats:p>","DOI":"10.3390\/antiox8090329","type":"journal-article","created":{"date-parts":[[2019,8,23]],"date-time":"2019-08-23T10:15:07Z","timestamp":1566555307000},"page":"329","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Inhibitory Effect of Nelumbo nucifera Leaf Extract on 2-Acetylaminofluorene-induced Hepatocarcinogenesis Through Enhancing Antioxidative Potential and Alleviating Inflammation in Rats"],"prefix":"10.3390","volume":"8","author":[{"given":"Mon-Yuan","family":"Yang","sequence":"first","affiliation":[{"name":"Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung 40201, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tung-Wei","family":"Hung","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Chung Shan Medical University Hospital, Taichung 40201, Taiwan"},{"name":"School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chau-Jong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Health Diet and Industry Management, Chung Shan Medical University, Taichung 40201, Taiwan"},{"name":"Department of Medical Research, Chung Shan Medical University Hospital, Taichung 40201, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsui-Hwa","family":"Tseng","sequence":"additional","affiliation":[{"name":"Department of Medical Applied Chemistry, Chung Shan Medical University, Taichung 40201, Taiwan"},{"name":"Department of Medical Education, Chung Shan Medical University Hospital, Taichung 40201, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,8,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1002\/hep.24710","article-title":"Hepatocellular carcinoma confirmation, treatment, and survival insurveillance, epidemiology, and end results registries, 1992\u20132008","volume":"55","author":"Altekruse","year":"2012","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/s41698-018-0048-z","article-title":"Role of nonresolving inflammation in hepatocellular carcinoma development and progression","volume":"2","author":"Yu","year":"2018","journal-title":"NPJ Precis. 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