In vitro anti-HIV-1 reverse transcriptase, cytotoxic activity, and tentative metabolite identification of Ziziphus mucronata Willd. bark and leaf extracts

Introduction: Human immunodeficiency virus (HIV) infection and cervical cancer continue to impose a substantial global health burden. Although combination antiretroviral therapy (cART) has markedly improved disease management, challenges including the emergence of resistant viral strains and treatment-associated toxicity highlight the ongoing need for alternative therapeutic strategies. In this study, we evaluated the in vitro inhibitory effects of Ziziphus mucronata bark and leaf extracts against HIV-1 reverse transcriptase (RT), together with their antiproliferative activity, apoptosis-inducing potential, and preliminary phytochemical composition. Cytotoxic activity was determined using the cervical cancer cell line ME180, while selectivity was assessed relative to non-malignant human embryonic kidney (HEK293) cells. Methods: Cell viability was quantified using Alamar Blue. The anti-viral activity was determined by measuring inhibition of HIV-1 reverse transcriptase. Apoptotic activity was evaluated through caspase-3/7 activation assays. Chemical profiling of the extracts was conducted using attenuated total reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy and gas chromatography-mass spectrometry (GC–MS) to identify functional groups and volatile constituents. Results: Both bark and leaf extracts demonstrated moderate inhibition of HIV-1 RT, with IC₅₀ values of 70 ± 0.23 µg/mL and 75 ± 0.39 µg/mL, respectively. Antiproliferative effects against ME180 cells were observed, yielding IC₅₀ values of 31 ± 2.25 µg/mL for the bark extract and 28 ± 0.97 µg/mL for the leaf extract. FTIR spectra indicated the presence of functional groups associated with phenolic compounds, aliphatic and aromatic hydrocarbons, carboxylic acids, and alcohols. GC–MS analysis detected 102 volatile constituents in the leaf extract and 16 in the bark extract. Conclusion: The results indicate that Z. mucronata contains metabolites with preliminary in vitro antiviral and anticancer properties. While these findings are limited to cell-based assays and tentative compound identification, they support further investigation of this species as a potential source of lead molecules for integrative medicinal application.