Regulation of Shigella effector kinase OspG by Musa acuminata fruit extracts: An in vitro, in vivo, and in silico study

The rising prevalence of antibiotic-resistant Shigella flexneri underscores the need for novel therapeutic strategies for the management of diarrheal disease. This study investigated the antidiarrheal potential of methanol extract (ME) and hot water extract (HWE) of Musa acuminata fruit using in vitro, in vivo, and in silico approaches. Phytochemical screening was performed using standard phytochemical screening methods. In vitro antibacterial activity against multidrug-resistant (MDR) S. flexneri was assessed by the disc diffusion method. In vivo S. flexneri -induced diarrhea was established in mice model. In silico analyses included molecular docking of phytochemical compounds with the S. flexneri effector protein kinase OspG using AutoDock Vina, followed by molecular dynamics (MD), simulations, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling. Significant phytocompounds were detected from ME and HWE. Both extracts demonstrated strong antibacterial potency with 24.83 ± 0.44 mm zone of inhibition, comparable to ciprofloxacin. In animal experiments, both extracts showed improved body weight, reduced diarrhea severity, and restored electrolyte balance, with HWE exhibiting greater efficacy. Molecular docking revealed that phytosterols remained stable throughout simulations. ADMET analysis indicated favorable safety profiles. Musa acuminata fruit extracts significantly mitigated S. flexneri -induced diarrhea through potent antibacterial activity and electrolyte restoration, supported by computational evidence of OspG inhibition. These findings position M. acuminata as a promising natural candidate for the development of antidiarrheal therapeutics. • Musa acuminata methanolic and aqueous extracts suppressed multidrug- resistant S. flexneri . • Extracts alleviated diarrheal symptoms by restoring electrolyte balance and body weight. • Phytochemical analysis revealed diverse secondary metabolites with therapeutic potential. • Phytosterols demonstrated high-affinity, stable interactions with OspG effector kinase. • ADMET profiling supported favorable pharmacokinetics and low predicted toxicity.