Ziziphus spina-christi leaves methanolic extract alleviates diethylnitrosamine-induced hepatocellular carcinoma in rats

Abstract

This study evaluated the antitumor activity of a methanolic extract from the leaves of Ziziphus spina-christi (ZSCL) against diethylnitrosamine (DENA)-induced hepatocarcinoma in rats. The phytochemical constituents, in vitro antioxidant and cytotoxic activities of ZSCL extract were investigated. Male Wistar rats were distributed among 6 groups: (i) normal control; (ii) ZSCL1-treated rats (100 mg/kg body mass; “b.m.”); (iii) ZSCL2-treated rats (300 mg/kg b.m.); (iv) rats with DENA-induced hepatocarcinoma; (v and vi) rats with hepatocarcinoma that were treated with either (v) ZSCL1 or (vi) ZSCL2. Serum liver function and levels of oxidative stress were assayed. The expression of hepatocyte growth factor, insulin-like growth factor-1 receptor, B cell lymphoma-2, and matrix metalloproteinase-9 oncogenes were quantified in liver samples. Histological examination of the liver tissues was performed. The ZSCL was rich in essential fatty acids, phytol, and polyphenolic flavones (luteolin and quercetin) with strong free-radical and peroxide scavenging activities and cytotoxic activity. Administration of ZSCL1 and ZSCL2 to the rats produced no toxic effects. DENA induced hepatocellular carcinoma and cholangioma by producing oxidative stress and upregulating the expression of hepatic oncogenes. Treatment of DENA-induced hepatocarcinoma with ZSCL2 ameliorated all of the abnormalities induced by DENA except for cholangioma. In conclusion, the ZSCL (300 mg/kg b.m.) displayed strong therapeutic activity against DENA-induced hepatocellular carcinoma via targeting oxidative stress and oncogenes.