Isolates From Thymelaea Hirsuta Inhibit Progression Of Hepatocellular Carcinoma In Vitro And In Vivo.

Herein, we investigated effect of Thymelaea hirsuta isolates on hepatocellular carcinoma. Methanolic extract of T. hirsuta led to isolation of two new compounds [6` hydroxyDaphnoretin (9) and Mithnin (15)], seven compounds reported for the first time from genus Thymelaea [Dotriacontanol (1), and 3-ketopentatriacontanoic (2), Docosylcoumarate (5), Docosylcaffeate (6), Daphnodorin B (11), 3`` -epi-dihydrodaphnodorin B (12) and Wikstaiwanone B (14)], and six known compounds. Eight compounds (5, 6, 9, 10, 11, 12, 14, and 15) showed significant anti-proliferative activity on HepG2 cells. These compounds caused significant reduction (p < 0.05) in serum levels of AST, ALT, ALP, total bilirubin, GGT, and AFP, a significant increase in Bax and p53 expression, and a significant decrease in Bcl2 gene in liver as compared to the HCC group. These results indicate that T. hirsuta isolates inhibited HCC progression, possibly through induction of apoptosis and therefore they could be used as a beneficial source for treating HCC.