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Antioxidants (Basel). 2019 Aug 22;8(9). pii: E329. doi: 10.3390/antiox8090329.

Inhibitory Effect of Nelumbo nucifera Leaf Extract on 2-Acetylaminofluorene-induced Hepatocarcinogenesis Through Enhancing Antioxidative Potential and Alleviating Inflammation in Rats.

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Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung 40201, Taiwan.
Division of Nephrology, Department of Medicine, Chung Shan Medical University Hospital, Taichung 40201, Taiwan.
School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan.
Department of Health Diet and Industry Management, Chung Shan Medical University, Taichung 40201, Taiwan.
Department of Medical Research, Chung Shan Medical University Hospital, Taichung 40201, Taiwan.
Department of Medical Applied Chemistry, Chung Shan Medical University, Taichung 40201, Taiwan.
Department of Medical Education, Chung Shan Medical University Hospital, Taichung 40201, Taiwan.


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 (0.5-2%) 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)-α as well as the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (γGT). NLE supplementation also reduced AAF-induced lipid peroxidation and 8-hydroxy-2'-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.


2-acetylaminofluorene; Nelumbo nucifera leaf extract; antioxidant enzymes; hepatocellular carcinoma; inflammation; oxidative stress

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