Exploring the anticancer properties of Azadirachta indica: In silico and in vitro study of its phytochemicals against hepatocellular carcinoma

The medicinal plant, Azadirachta indica (Neem), has been found to interfere with the carcinogenesis process and act as a tumor suppressor. This study evaluated the anti-cancer properties of methanol extract from Azadirachta Indica against the human hepatocellular carcinoma cell line (HepG2) using the in vitro MTT assay. The results demonstrated that the methanol extract of Azadirachta Indica exhibited significant cytotoxicity against HepG2 cells, with an IC50 value of 81.17 µg/ml. Furthermore, an in silico approach was used to investigate the interaction between Azadirachta indica and Akt1, a protein kinase implicated in the pathogenesis of hepatocellular carcinoma (HCC) via the PI3K/Akt/mTOR pathway. The study identified two promising Akt1 inhibitors, 2′,3′-Dehydrosalannol, and Quercetin, with an improved binding affinity (ΔGbind) and a safe pharmacological profile. These compounds also showed hepatoprotective actions. Molecular dynamics simulations, specifically the MM-GBSA model, were used to further scrutinize the inhibitory potential of the docked bio-constituents. The results suggest that the proposed in silico pipeline can be useful in identifying lead candidates for HCC through early-stage rational drug design. These candidates can then be verified in vitro and in vivo before being tested in clinical trials as a mainstream target against HCC.