Neuromodulatory efficacy of Bacopa monniera extract against streptozotocin-induced neuronal dysfunction in SH-SY5Y cells: Implications for diabetic neuropathy.

Diabetic neuropathy (DN), a major complication of diabetes mellitus, is characterized by progressive neuronal damage driven by hyperglycemia-induced oxidative stress, mitochondrial dysfunction, and advanced glycation end product (AGE) accumulation. Bacopa monniera (Scrophulariaceae), enriched with the neuroactive saponin Bacoside A (BA), has demonstrated neuroprotective potential. This study explored the molecular mechanisms underlying the neuroprotective effects of B. monniera extract (BME) against streptozotocin (STZ)-induced toxicity in SH-SY5Y neuroblastoma cells. In silico ADMET analysis revealed that BA and its sapogenins possess favorable pharmacokinetic profiles, including enhanced absorption, reduced toxicity, and improved clearance, supporting their bioactive role in BME. Pretreatment with BME (25 μg/mL) significantly (p < 0.01) reduced STZ-induced mitochondrial (51.24 %) and membrane (41.69 %) damage, as shown by MTT and LDH assays. BME markedly reduced intracellular ROS, protein carbonylation, and lipid peroxidation (p < 0.001), while restoring mitochondrial membrane potential, ATP levels, enzymatic antioxidant levels, and glutathione content. Furthermore, BME upregulated brain-derived neurotrophic factor (BDNF) expression and inhibited AGE formation. Collectively, these findings highlight the antioxidant, antiglycation, and neurotrophic actions of BME, underscoring its promise as a multi-targeted phytotherapeutic candidate for DN management.