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

Abstract

Introduction: Ziziphus mucronata is widely used in African traditional medicine to manage conditions such as diarrhoea, cough, and wound-related ailments. Extracts from this plant have also shown potential antiviral and cytotoxic activities. This study thus evaluated the in vitro anticancer and anti-HIV potential of bark and leaf extracts of Z. mucronata and performed tentative identification of their bioactive metabolites. Cytotoxicity was assessed against the cervical cancer cell line ME180, and selectivity indices were calculated using non-cancerous human embryonic kidney cells (HEK293). Methods: Cytotoxic effects of the extracts were measured using the Alamar Blue assay, while anti-HIV activity was evaluated through inhibition of HIV-1 reverse transcriptase (RT). Apoptosis induction was examined via caspase-3/7 activity assays. Phytochemical profiling was performed using attenuated total reflection Fourier-transform infrared attenuated total reflectance (FTIR-ATR) spectroscopy and gas chromatography–mass spectrometry (GC-MS). Results: Both bark and leaf extracts showed moderate inhibition of HIV-1 RT, with IC50 values of 70 ± 0.23 µg/mL and 75 ± 0.39 µg/mL, respectively. Cytotoxicity against ME180 cells was favorable, with IC50 values of 31 ± 2.25 µg/mL (bark) and 28 ± 0.97 µg/mL (leaf). FTIR analysis indicated the presence of phenols, alkenes, alkanes, carboxylic acids, hydroxyls, alcohols, and aromatic compounds. GC-MS profiling identified 102 volatile compounds in leaf extracts and 16 in bark extracts. Conclusions: These findings suggest that Z. mucronata contains bioactive metabolites with preliminary in vitro anticancer and anti-HIV activity. Although results are limited to in vitro observations and tentative metabolite identification, they support further exploration of this plant as a potential source of lead compounds for integrative medicine research.