Bioprospecting the brain protective activity of Bryophyllum pinnatum leaf: Ex-vivo study and molecular docking- interaction analysis

The neuroprotective effects of Bryophyllum pinnatum leaf extract (BPLExt) were investigated against iron-mediated neurotoxicity in isolated rats’ brains using an ex vivo model. Protective effects of BPLExt on brain homogenate were evaluated using increasing concentrations (50–250 μg/mL) cocultured in the presence of 0.1 mM FeSO₄. As expected Fe2+-mediated neurotoxicity led to reduction of glutathione, catalase, superoxide dismutase, and E-NTPDase activities, while malondialdehyde (MAL) and nitric oxide (NO) levels, ATPase, acetylcholinesterase and α-chymotrypsin activities increased concurrently. Co-incubation with BPLExt significantly (p < 0.05) reversed Fe2+-mediated neurotoxicity for all of the tested oxidative markers and enzymes. Toxicity evaluation of BPLExt displayed a non-cytotoxic effect on the (HT22) cell line. GC–MS analysis revealed sixty (60) potential phytochemical inhibitors when it was used to analyse BPLExt. Using computational tools, we then screened for compounds with high binding affinity for ATPase, Acetylcholinesterase, CAT, and NO synthase (NOS). Selected compounds showed promising binding affinities such as Cpd60 (-6.34 kcal/mol for ATPase), Cpd32 (-10.38 kcal/mol for Acetylcholinesterase), and Cpd25 (-9.02 kcal/mol for Catalase, -8.05 kcal/mol for NOS), with several outperforming Donepezil (control). Taken together, BPLExt demonstrated promising antioxidant activities, inhibited cholinergic and proteolytic activities, and acted as a modulator of purinergic activity. Protein-ligand interaction analysis revealed key residue engagements, confirming the compounds' binding efficacy. These findings highlight BPL potential for multi-target drug development in neurodegeneration, warranting further validation.