Ayurvedic Herbs as neurogenesis modulators: Current understanding on their potential therapeutic relevance in enhancing neuroplasticity and cognition in aging and neurodegeneration.

Ayurvedic medicine, an ancient Indian health system, promotes a category of Ayurvedic herbs (AH) known as Medhya Rasayanas (nootropic rejuvenators) for cognitive enhancement and neuroprotection. Currently, AH are increasingly being studied for their potential to boost neuroplasticity and neurogenesis, as they can stimulate the growth of new neurons, improve the complexity of existing ones, and support cognitive resilience. Recent evidence-based research suggests the potential to use these AH and their formulations to develop new therapies for addressing cognitive decline during aging and neurodegenerative disorders (NDD). Neurogenesis is known to be compromised in mild cognitive impairment (MCI) and is impaired early in animal models of Alzheimer's disease (AD), suggesting that rescuing neurogenesis may restore hippocampal plasticity and attenuate neuronal vulnerability and memory loss. Several AH, including Brahmi (Bacopa monnieri), Gotu Kola (Centella asiatica), Ashwagandha (Withania somnifera), Shankhapushpi (Convolvulus pluricaulis), Guduchi (Tinospora cordifolia), and Yashtimadhu (Glycyrrhiza glabra), are well recognized for their cognitive-enhancing and neuroprotective properties. Further, in chronic stress models, the neurogenic effects of AH are proposed to be mediated by mechanisms including antioxidant and anti-inflammatory effects, modulation of neurotransmitters, and effects on the gut microbiota. Neurotrophins (particularly brain-derived neurotrophic factor -BDNF) are important mediators of neuroplasticity as they modulate multiple processes, including synaptic plasticity, axonal and dendritic growth, spine morphogenesis, and neurogenesis. BDNF is compromised in depression and recovered by conventional antidepressants. The antidepressant-like effects of AH are associated with the reversal of chronic stress-induced impairment in neuroplasticity, most notably through up-regulation of BDNF, activation of downstream signaling pathways, and increased neurogenesis in the hippocampus and/or prefrontal cortex. This review summarizes current developments regarding AH's propensity to enhance neuronal plasticity and its therapeutic role as a modulator of neurogenesis. It also emphasizes the importance of using them as adjuvant therapy to attenuate cognitive deficits associated with aging and neurodegeneration.