Mechanistic insight into neuroprotective effect of standardized ginger chemo varieties from Manipur, India in scopolamine induced learning and memory impaired mice.

Abstract

Alzheimer's disease is a complex neurodegenerative disease characterized by progressive decline in cognitive function and behaviour. Ginger is the rhizome of the plant Zingiber officinale Roscoe, has been an important ingredient of many Ayurveda formulations to treat neurological disorders. The present study aims to estimate the variation of 6-gingerol content in nine different ginger samples collected from Manipur, India, investigate the neuroprotective potential of the most potent ginger sample against scopolamine-induced cognitively impaired mice, and validate the therapeutic claim by molecular docking analysis. High Performance Thin Layer Chromatography (HPTLC) analysis suggested that the sample GV6 had the highest 6-gingerol content with potent in vitro acetylcholnesterase (AChE) (IC50 = 336.10 µg/mL) and butyrylcholinesterase (BChE) (IC50 = 411.73 µg/mL) enzyme inhibitory activity. The neuroprotective potential of GV6 was tested in scopolamine-induced cognitively impaired mice (200 and 400 mg/kg). The behavioral analysis showed that GV6 alleviated the spatial recognition, and short-term and long-term memory in the experimental mice model. GV6 significantly improved brain AChE and BChE activity, acetylcholine (ACh) level, markedly alleviated the antioxidant parameters, and reversed the neuroinflammation. Brain histopathological observations confirmed the presence of organized nerve fibers, improvement of neuronal cell density, and reverse the nucleus shrinkage. Further molecular docking analysis showed that 6-gingerol and galantamine exhibited stable interaction with AChE (-7.5 and - 7.3 kcaL/moL) and BChE (-7.3 and - 8.5 kcaL/moL). The present study emphasizes the quality-related therapeutic importance of ginger samples from Northeast India and demonstrates that administration of GV6 may improve brain cognitive functions by restoring neurotransmitter levels and inflammatory and antioxidant parameters in scopolamine-induced cognitively impaired mice.