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.