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Erucaria pinnata (Viv.) is a wild annual plant growing in North-Western Coastal Region in Egypt. This study reports for the first time the cytotoxic activity of different extracts of Erucaria pinnata plant against HEP-G2 cell line. The 70% methanolic extract (E1) recorded the best potent cytotoxic activity (IC50=13.6 µg/ml), so we analysis the flavonoids constituent of this extract using HPLC, which show that our extract is rich with important flavonoids compounds (rutin, quercetin, leutolin, etc.). We evaluated its antitumor activity against hepatocellular carcinoma (HCC) induced by diethylnitrosamine (DEN) (200mg/Kg. b.wt., i.p, single dose) after two weeks, animals received carbontetrachloride (CCl4) (3ml/Kg. b.wt., SC, once a week for 6 weeks) and the experiment continued for 44 weeks in rats. After the experimental period, the administration of DEN/CCl4 showed significant increase in the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin, gamma-glutamyl transferase (γGT) and significant decrease in the levels of total proteins and albumin content in the serum with reduction in the liver antioxidants, including superoxide dismutase (SOD) and catalase (CAT). This was accompanied by increases in serum specific tumor markers (AFP). The 70% methanolic plant extract (E1) was orally administrated (400mg/kg/day respectively) for the whole study period, and it showed a significant improvement at the different biological liver functions, remodeled the antioxidant enzymes activity and down-regulated the serum AFP. All these findings were confirmed by histopathological studies of the liver samples obtained from all groups. In addition, we evaluated its antiangeogenic activity by docking study against VEGFR-2 tyrosine kinase after it showed an ability to inhibit the VEGFR-2 expression in vitro and inhibit the concentration of VEGF-A in vivo. The hepatoprotective effect of our extract was attributed to its antioxidant and antiangeogenic activity.
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