Neuroprotective Effects of Bauhinia variegata Flower Extract against D-Galactose-Induced Age-Related Cognitive Impairment: Modulation of the Oxidative Stress-endoplasmic reticulum Axis.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Bauhinia variegata is widely used in traditional medicine for the management of disorders associated with inflammation, oxidative stress, and nervous system dysfunction. The presence of flavonoids and phenolics supports its ethnopharmacological relevance to cognitive impairment, both reported to exert neuroprotective, antioxidant, and cholinesterase-inhibitory activities
Aim
OF THE STUDY: The present study investigated the neuroprotective potential of B. variegata flower ethanolic extract (BV-EtOH) against D-galactose (D-Gal)-induced age-related cognitive impairment in rats, with emphasis on its anti-inflammatory, antioxidant, and anti-tauopathic mechanisms.
Results
Chronic D-Gal administration (120 mg/kg) for 8 consecutive weeks induced significant oxidative stress, neuroinflammation, and cognitive impairment, whereas BV-EtOH treatment (50, 100, and 200 mg/kg, p.o., 8 weeks) markedly reversed these alterations. BV-EtOH improved learning and memory by reducing escape latency in the Morris Water Maze by 56.3% and increasing target quadrant time by 48.7% (p < 0.01), while the Object Recognition Test showed a 61.4% rise in discrimination index. Biochemically, BV-EtOH restored GSH levels (74.2%) and reduced MDA (63.5%), alongside significant down regulation of TNF-α (52.8%), IL-1β (47.9%), NF-κB (45.6%), and Endoplasmic reticulum (ER) stress mediators GRP78, CHOP, and P-PERK (58-67%) (p < 0.001). Notably, p-Tau expression decreased by 54.1% with concurrent inhibition of GSK-3β, while BDNF and NeuN increased by 2.3- and 2.7-fold, respectively, indicating enhanced neurogenesis and synaptic integrity. UPLC-ESI-MS/MS analysis identified 133 bioactive compounds, mainly flavonoids, phenolic acids, proanthocyanidins, and coumarins, collectively contributing to the extract's multitarget modulation of oxidative, inflammatory, ER stress, and tau phosphorylation pathways.
Conclusion
These findings demonstrate that BV-EtOH exerts potent neuroprotective efficacy and holds therapeutic promise for the prevention and management of neuroinflammatory and neurodegenerative disorders.