In vitro antibacterial activity and in silico validation of phytocompound Emodin from Rheum Emodi Wall. Ex Meissn....

Antimicrobial resistance continues to outpace the development of new antibiotics, creating an urgent need for alternative antibacterial agents. We evaluated Emodin, a plant-derived phytocompound, for antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant (MDR) Enterobacter cloacae. Emodin demonstrated inhibitory activity against both organisms with a minimum inhibitory concentration (MIC) of 0.156 mg/mL and bactericidal activity at higher concentrations, with minimum bactericidal concentrations (MBCs) of 1.25 mg/mL for MRSA and 2.5 mg/mL for MDR E. cloacae. In growth-curve experiments, Emodin produced sustained, time-dependent suppression of bacterial growth relative to untreated controls. Stability testing showed preserved antibacterial activity at 4 °C to 50 °C, reduced activity at 80 °C to 100 °C, and reduced activity under acidic conditions, with relative stability at neutral to alkaline pH. Mechanistic studies consistently supported membrane-targeting effects, including increased release of nucleic acids and cytoplasmic proteins, marked ultrastructural damage on scanning electron microscopy (SEM), and enhanced propidium iodide (PI) uptake, indicating compromised membrane integrity. In silico docking suggested favorable binding of Emodin to S. aureus Sortase A (- 7.4 kcal/mol) and the E. cloacae LptBFGC complex (- 6.4 kcal/mol). SwissADME profiling further supported drug-likeness, with high predicted gastrointestinal absorption and no Lipinski rule-of-five violations. Collectively, these findings position Emodin as a promising phytocompound and a strong candidate for the development of plant-based therapeutics targeting MDR pathogens, warranting further validation across a broader range of resistant clinical isolates and in vivo safety and efficacy profiling.