Network pharmacology reveals Artemetin from Artemisia annua as a multitarget agent against hepatocellular carcinoma with α-amylase-inhibitory potential
摘要
Limited research has been conducted on the mechanistic action of Artemisia annua against hepatocellular carcinoma (HCC) and associated comorbidities, underscoring its potential as a flagship traditional plant for future pathological investigations. This study employed an integrative network pharmacology approach to elucidate the interplay between key metabolites, therapeutic targets, and HCC-modulated pathways. Our findings identified artemisinin as the predominant bioactive compound, exerting regulatory effects through critical targets such as AKT1, EGFR, HSP90AA1, and ESR1. Molecular docking revealed robust binding interactions between artemetin and these targets, with docking scores ranging from –9.5 to –17.4 kcal/mol, supported by low RMSD values (< 2.0 Å), indicative of stable complexes. UHPLC‒MS analysis of the methanol-based extract revealed multiple anticancer and antidiabetic compounds, predominantly flavonoids. In vitro validation demonstrated significant dose-dependent inhibition of HepG2 cell viability (up to 96.25% ± 0.5 reduction at 200 μM) and notable α-amylase inhibitory activity (30.22% at 1 µg/mL), albeit less potent than that of acarbose. Collectively, our in silico and experimental results provide a mechanistic foundation for the anti-HCC and antidiabetic potential of Artemisia annua, highlighting its multitarget therapeutic properties. These findings warrant further validation through in vitro and in vivo studies to advance its clinical application.