Evaluation of the hepatoprotective effects of anthraquinone in a rat model of liver cancer

Abstract

Studies on Rhubarb officinale L, family Polygonacea ( R. officinale ) crude extract (RCE) and isolated anthraquinones (aloe-emodin, emodin, rhein, chrysophanol, and physcion) show conflicting effects on the liver, with some suggesting protection and others toxicity. This study aimed to investigate the hepatoprotective effects of R. officinale free anthraquinone fraction (ANF) on diethylnitrosamine (DEN) + carbon tetrachloride (CCl 4 )-triggered hepatocellular carcinoma (HCC) when given individually or with sorafenib (SOR) in rats. Forty-two adult male albino rats were divided into six groups: control, control ANF, HCC model (DEN + CCl4), HCC + ANF (100 mg/kg/day oral), HCC + SOR (10 mg/kg/day oral), and HCC + ANF + SOR. HCC was confirmed via elevated serum alpha-fetoprotein (AFP) and histopathology. AFP, apoptosis markers (Bax, Bcl2, caspase-3), oxidative stress (ROS, Nrf2, HO-1), proliferation markers [proliferating cell nuclear antigen (PCNA) and glypican3 (GPC3)], and histopathology were evaluated using ELISA, RT-qPCR, immunohistochemistry, and H&E staining. Rats treated with ANF and/or SOR had a decreased HCC burden as evidenced by 1) decreased relative liver weight; 2) reduced serum levels of AFP; 3) higher apoptosis (high Bax and caspase 3, and low Bcl2 ); 4) declined number of abnormal hepatic foci; 5) decreased PCNA and GPC3 immune-staining reactivity in the liver; and 6) low intracellular ROS, and higher expression of the two antioxidant-related genes Nrf2 and HO-1 . The combined treatment with ANF and SOR gave better hepatic improvement than the individual treatments. With these results, we could conclude that treatment with ANF and/or SOR decreased the HCC burden by triggering apoptosis and inhibiting oxidative stress in HCC. Therefore, the ANF/SOR combination could be a novel therapeutic strategy against HCC.