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

Abstract

The medicinal plant Azadirachta indica (Neem) interferes with carcinogenesis and acts as a tumor suppressor. This study evaluated the anticancer effects of a methanol extract of Azadirachta Indica on a human hepatocellular carcinoma cell line (HepG2) using an 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. This study identified two promising Akt1 inhibitors, 2′,3′-dehydrosalannol and quercetin, with improved binding affinity (ΔGbind) and a safe pharmacological profile. These compounds also showed hepatoprotective effects. Molecular dynamics simulations, specifically the MM-GBSA model, were used to further scrutinize the inhibitory potential of the docked bioconstituents. The results suggest that the proposed in silico pipeline can be useful for 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 mainstream targets against HCC.