Abstract
Background: Oral dysbiosis is a key driver of dental caries, periodontal disease, and persistent endodontic infections. Increasing antimicrobial resistance has prompted the exploration of plant-based alternatives. Objective: To evaluate host-dependent variation in the antimicrobial activity of Tinospora cordifolia against oral pathogens. Methods: Methanolic extracts of T. cordifolia growing on host plants Azadirachta indica, Saraca asoca, and Citrus limon, along with a control sample, were evaluated using agar well diffusion at 50-200mg/Ml.MIC and MBC were determined. Statistical analysis was performed using one-way ANOVA with Tukey’s post-hoc test. Molecular docking was performed for major phytocompounds against bacterial target protein. Results: Significant host-dependent variation was observed F (3, 12) = 24.78, (p < 0.001). Neem-hosted extracts exhibited maximum inhibition against Staphylococcus aureus (22 mm), whereas Lemon-hosted extracts showed superior activity against Enterococcus faecalis (21 mm). A clear concentration-dependent increase in antimicrobial activity was observed from 50-200 mg/mL across all extracts. Post-hoc analysis revealed Neem and Lemon extracts were significantly more effective than Ashoka and Normal giloy p<0.01. Furthermore, molecular docking simulated interactions between bioactive ligands and bacterial survival proteins, with Quercetin showing strong binding to E. coli DHFR (-9.6 kcal/mol). Conclusion: Host plant significantly modulates the antimicrobial profile of T. cordifolia, suggesting its potential for developing targeted herbal therapeutics for oral infections. These findings suggest that host-modulated T. cordifolia offers a customizable natural scaffold for precision management of oral dysbiosis.