In-Vivo and In-Silico analysis of Ficus carica-based acetone extract against the DEN-induced hepatocellular carcinoma.

Abstract

Hepatocellular carcinoma (HCC) is one of the most fatal cancers responsible for mortality worldwide. For the first time, a randomized controlled study was conducted on 32 Balb c albino mice to evaluate the anticancer potential of the acetone-based extract of F. carica variety from Shandong province of China. Diethylamine nitrosamine (DEN) and carbon tetrachloride (CCl₄) were used as inducers of hepatic carcinoma in mice. We conducted an in vivo study on F. carica-based acetone (FA) extract that has already been proven effective against hepatoblastoma cancer (HepG2) cell lines in our previous experiments. The FA extract (60mg/kg) significantly attenuated serum levels of liver functional biomarkers (BUN, ALT, AST, ALP) and alpha-fetoprotein (AFP) in mice. Histopathological analysis revealed that the extract promoted liver tissue regeneration, restoring near-normal hepatic architecture after 60 days of treatment. Silymarin (50mg/kg), used as a positive control, similarly reduced liver injury biomarkers. Notably, the extract demonstrated comparable efficacy to silymarin, with significant reductions in serum BUN and AST levels. Complementing our in vivo results, in silico molecular docking and ADMET profiling revealed FA-derived phytochemicals (e.g., sitosterol, quercetin, luteolin) with efficacy rivaling or exceeding silymarin. These compounds exhibited strong binding affinities to hepatocellular carcinoma targets such as EGFR, VEGFR, and MMPs, thus suggesting multi-target therapeutic potential. The findings suggest that sitosterol, quercetin, and luteolin show competitive binding and favorable ADMET properties, proposing them as candidates for further experimental validation. This novel extract and its isolated compounds may represent a more effective and cost-efficient alternative to conventional hepatoprotective drugs for future therapeutic applications.