Investigations on a polyherbal formulation for treatment of cognitive impairment in a cholinergic dysfunctional...

Alzheimer's disease is a multifactorial neurodegenerative condition manifested through acute cognitive decline, amyloid plaque deposits and neurofibrillary tangles. Complete cure for this disease remains elusive as the conventional drugs address only a single molecular target while Alzheimer's disease involves a complex interplay of different sets of molecular targets and signaling networks. In this context, the possibility of employing multi-drug combinations to rescue neurons from the dysregulated metabolic changes is being actively investigated. The present work investigates a poly-herbal formulation, Brahmi Nei that has been traditionally used for anxiolytic disorders and immunomodulatory effects, for its efficiency in ameliorating cognitive decline through a combination of behavioral, biochemical, histopathological, gene and protein expression analyses. Our results reveal that the formulation shows excellent neuroregenerative properties, rescues neurons from inflammatory damage, reduces neuritic plaque deposits and improves working memory in rodent models with scopolamine-induced dementia. The microarray analysis shows that the formulation induces the expression of pro-survival pathways and positively modulates genes involved in memory consolidation, axonal growth and proliferation in a concentration-dependent manner with therapeutic concentrations restoring the normal conditions in the brain of the diseased animals. The neuritic spine morphology confirms the long-term memory potentiation through improved mushroom spine density, increased dendritic length and connectivity. Taken together, our study provides mechanistic evidence to prove that the traditional formulation can be a superior therapeutic strategy to treat cognitive decline when compared to the conventional mono-drug treatment.