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Therapeutic strategies for neurodegenerative disorders emphasize on identification of compounds that can rebuild loss of neuronal connectivity as well enhance the existing framework. Hindrance of blood brain barrier (BBB) permeability poses a major pharmacological challenge leading to inefficacy of FDA approved drugs like Rivastigmine. Therefore focus is shifting to multi targeted and less toxic herbal compounds. Previously, we reported that Bacosides (active component of Bacopa monniera) encapsulated in targeted Lactoferrin-conjugated tri-block PEGPLA-PCL-OH polymersomes (BAN) was more efficient in restoring scopolamine impaired memory than its natural form. Given the concept of higher therapeutic efficacy of polyherbal formulations, here we investigated the coadministering effect of BAN and coconut oil derived Lauric acid encapsulated in targeted Lactoferrin-conjugated tri-block PEG-PLA-PCL-OH polymersomes (LAN) on scopolamine challenged neurons. BAN and LAN coadministration showed marked neuroprotection and also promoted neurogenesis, neurodifferentiation, neuritogenesis and neurite elongation of mouse neuroblastoma and primary neuronal cells. Cellular changes were accompanied with upregulation of neurotrophic factor BDNF and neuronal activity dependent Arc gene expression. Further, investigations into epigenetic changes, pivotal for neural cell fate determination and differentiation revealed DNMTs (DNA (cytosine-5)-methyltransferase) and HDACs (Histone deacetylases) inhibition by BAN and LAN combined treatment. Overall our study revealed neuroprotection and neuroenhancement by BAN-LAN combination better than Rivastigmine and Rivastigmine encapsulated in Lactoferrin-conjugated tri-block PEG-PLAPCL-OH polymersomes (RiN) possibly through epigenetic modification of neuronal genes. [ABSTRACT FROM AUTHOR]

Age-associated cognitive decline is an inevitable phenomenon that predisposes individuals for neurological and psychiatric disorders eventually affecting the quality of life. Scientists have endeavored to identify the key molecular switches that drive cognitive decline with advancing age. These newly identified molecules are then targeted as recovery of cognitive aging and related disorders. Cognitive decline during aging is multi-factorial and amongst several factors influencing this trajectory, gene expression changes are pivotal. Identifying these genes would elucidate the neurobiological underpinnings as well as offer clues that make certain individuals resilient to withstand the inevitable age-related deteriorations. Our laboratory has focused on this aspect and investigated a wide spectrum of genes involved in crucial brain functions that attribute to senescence induced cognitive deficits. We have recently identified master switches in the epigenome regulating gene expression alteration during brain aging. Interestingly, these factors when manipulated by chemical or genetic strategies successfully reverse the age-related cognitive impairments. In the present article, we review findings from our laboratory and others combined with supporting literary evidences on molecular switches of brain aging and their potential as recovery targets. [ABSTRACT FROM AUTHOR]

Preclinical studies on animal models have discerned the antiamnesic and memory-enhancing potential of Bacopa monniera (Brahmi) crude extract and standardized extracts. These studies primarily focus on behavioral consequences. However, lack of information on molecular underpinnings has limited the clinical trials of the potent herb in human subjects. In recent years, researchers highlight plasticity markers as molecular correlates of amnesia and being crucial to design therapeutic targets. In the present report, we have investigated the effect of a special extract of B. monniera (CDRI-08) on the expression of key neuronal (BDNF and Arc) and glial (GFAP) plasticity markers in the cerebrum of scopolamine induced amnesic mice. Pre- and postadministration of CDRI-08 ameliorated amnesic effect of scopolamine by decreasing acetyl cholinesterase activity and drastically upregulating the mRNA and protein expression of BDNF, Arc, and GFAP in mouse cerebrum. Interestingly, the plant extract per se elevated BDNF and Arc expression as compared to control but GFAP was unaltered. In conclusion, our findings provide the first molecular evidence for antiamnesic potential of CDRI-08 via enhancement of both neuronal and glial plasticity markers. Further investigations on detailed molecular pathways would encourage therapeutic application of the extract in memory disorders. [ABSTRACT FROM AUTHOR]