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

 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 7,12-Dimethylbenz(α) anthracene (DMBA)-induced cell proliferation in female rats.

Forty female Sprague Dawley rats averaging 110 ± 20 g were induced proliferation with DMBA (80 mg/kg) and treated with ethyl acetate fraction (250 mg/kg BW) of O. subscorpioidea or tamoxifen (6.6 mg/kg BW) before and after induction. The trial lasted 22 weeks. In-vivo antioxidant parameters such as superoxide dismutase (SOD), malondialdehyde (MDA), and reduced glutathione (GSH) were examined. Likewise, carcinoma antigen marker (CA153), and DNA methyltransferase 3-like (DNMT3L) 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.

Treatment with OSEA significantly increased the SOD activity, enhanced GSH levels, and lowered the levels of MDA, CA-153, and DNMT3L in DMBA-exposed rats. The GC-MS analysis of OSEA revealed the presence of 40 bioactive compounds. The molecular docking revealed that 4-cyclopentene-1,3-dione (-6.407 kcal/mol), 2-(2-hydroxyethylthio) (-4.926 kcal/mol) and 3,4,5,6-tetrahydrophthalic anhydride (-6.16 kcal/mol) had the lowest binding energies against DNMT1, DNMT3A, and DNMT3B, respectively. 2-(2-hydroxyethylthio) was the least toxic. The molecular dynamic simulation revealed that the interaction between DNMT3A and 2-(2-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.