Anti-HIV-1 potential of Tinospora cordifolia extracts: Multi-targeted viral inhibition and immune landscape modulation

Background and Aim Despite the success of antiretroviral therapy, HIV-1 remains a formidable global health challenge due to drug toxicity, resistance, and persistent immune dysfunction. Tinospora cordifolia (TC), an Ayurvedic Rasayana herb, holds immense promise as a phytotherapeutic alternative owing to its dual antiviral and immunomodulatory potential. This study investigated the anti-HIV-1 efficacy and the mechanistic basis of TC extracts. Experimental procedure Hydroalcoholic (HATC) and aqueous (AQTC) extracts of TC were evaluated in vitro using TZM-bl cells and primary human PBMCs infected with HIV-1 primary isolates. Antiviral activity, cytotoxicity, viral enzyme inhibition, and immunomodulatory effects were assessed through luciferase assays, ELISA, qRT-PCR, immunoblotting, and cytokine profiling. Molecular docking was performed to identify bioactive phytoconstituents targeting key HIV-1 enzymes. Results and Conclusion Both TC extracts exhibited potent, dose-dependent anti-HIV-1 activity, with HATC showing superior efficacy. HATC inhibited HIV-1 protease and reverse transcriptase, suppressed GAG, TAT, and p24 expression, and modulated macrophage cytokine profiles by controlling IL-1β, IL-6, TNF-α, IL-10, and TGF-β. Notably, HATC may upregulate STING–IFN-β signalling, suggesting enhanced innate antiviral defence. Molecular docking revealed strong binding affinities of columbin, tinosporide, and tinosporaside with HIV-1 protease and reverse transcriptase. Experimental validation confirmed that columbin demonstrated potent anti-HIV-1 activity. This is the first comprehensive study to demonstrate that TC extract exerts multi-targeted inhibition of HIV-1 replication and restores immune balance. These findings support its development as a novel adjunct phytotherapy for HIV-1 and warrant further pre-clinical investigation.