In-silico and biochemical analysis of ethyl acetate fraction of Olax subscorpioidea leaf on DMBA-induced cell proliferation in female rats

Introduction: Olax subscorpioidea is a medicinal plant that Africans use to treat numerous ailments, including cancer. This research examines the antioxidant, anticancer, and in-silico properties of ethyl acetate fraction of Olax subscorpioidea’s (OSEA) on ۷,۱۲-Dimethylbenz(α) anthracene (DMBA)-induced cell proliferation in female rats. Methods: Forty female Sprague Dawley rats averaging ۱۱۰ ± ۲۰ g were induced proliferation with DMBA (۸۰ mg/kg) and treated with ethyl acetate fraction (۲۵۰ mg/kg BW) of O. subscorpioidea or tamoxifen (۶.۶ mg/kg BW) before and after induction. The trial lasted ۲۲ weeks. In-vivo antioxidant parameters such as superoxide dismutase (SOD), malondialdehyde (MDA), and reduced glutathione (GSH) were examined. Likewise, carcinoma antigen marker (CA۱۵۳), and DNA methyltransferase ۳-like (DNMT۳L) activity were measured. Gas chromatography-mass spectrometry (GC-MS) detected the bioactive compounds, and molecular docking studies predicted the mechanism of action of OSEA against DNA methyltransferase. Results: Treatment with OSEA significantly increased the SOD activity, enhanced GSH levels, and lowered the levels of MDA, CA-۱۵۳, and DNMT۳L in DMBA-exposed rats. The GC-MS analysis of OSEA revealed the presence of ۴۰ bioactive compounds. The molecular docking revealed that ۴-cyclopentene-۱,۳-dione (-۶.۴۰۷ kcal/mol), ۲-(۲-hydroxyethylthio) (-۴.۹۲۶ kcal/mol) and ۳,۴,۵,۶-tetrahydrophthalic anhydride (-۶.۱۶ kcal/mol) had the lowest binding energies against DNMT۱, DNMT۳A, and DNMT۳B, respectively. ۲-(۲-hydroxyethylthio) was the least toxic. The molecular dynamic simulation revealed that the interaction between DNMT۳A and ۲-(۲-hydroxyethylthio) propionic was stable to an extent. : The in-silico and biochemical analysis of the ethyl acetate fraction of O. subscorpioidea showed that it can protect against lipid peroxidation and oxidative stress and may be a potent source of drug that serves as an effective therapeutic in the future.