A network pharmacological approach for the identification of potential therapeutic targets of Brahmi Nei - a complex traditional Siddha formulation.

Brahmi Nei (BN), a traditional Indian polyherbal formulation has been described in classical texts for the treatment of anxiety and depression, as well as to fortify the immune system. The individual herbs of BN have been used for treatment of wide range of disorders including cognition, inflammation, skin ailments and cancer etc., This diverse basket of therapeutic activity suggests that BN may possess therapeutic benefits to other disorders. So, the present study aims to identify the potential therapeutic targets of BN using a network pharmacological approach to comprehend the multi target action of its multiple phytoconstituents. We have employed Randic Index for the first time to calculate the contribution score of module segregated targets towards diseases. Our results suggests that BN targets could also be effective in other diseases such as lysosomal storage disorders, respiratory disorders etc., apart from neurological disorders. The key targets with highest topological measures of Targets-(Pathway)-Targets network were identified as potential therapeutic targets of BN. And the top hit target PTGS2, a gene encoding for cyclooxygenase-2 was further evaluated using molecular docking, molecular dynamic simulation and in vitro studies. Our findings open up new therapeutic facets for BN that can be explored systematically in future.Communicated by Ramaswamy H. Sarma.

Towards understanding the mechanism of action of a polyherbal formulation using a multi-pronged strategy.

Herein, we investigate the cognitive effects of a traditional polyherbal formulation, Brahmi Nei (BN) for its effect on cognitive health. Network pharmacological analysis of the bioactives reported in the phytoconstituents of BN was performed by retrieving information from various databases. The in-silico predictions were experimentally validated using in vitro and in vivo models through a combination of biochemical, behavioural and molecular studies. The network pharmacological analysis of the key molecules in BN revealed their ability to modulate molecular targets implicated in memory, cognition, neuronal survival, proliferation, regulation of cellular bioenergetics and oxidative stress. Behavioral studies performed on normal adult rats administered with BN showed a significant improvement in their cognitive performance. Microarray analysis of their brain tissues exhibited an up-regulation of genes involved in oxidative phosphorylation, learning, neuronal differentiation, extension, regeneration and survival while pro-inflammatory and pro-degenerative genes were down-regulated. The oxygen consumption rate in BN-treated hippocampal cells showed a significant improvement in the bioenergetic health index when compared to untreated cells due to the mitochondrial membrane fortifying effect and anti-inflammatory property of the BN constituents. The neuroregenerative potential of BN was manifested in increase in axonal length and neurite outgrowth. Western blots and 2D gel electrophoresis revealed a reduction in pro-apoptotic proteins while increasing Akt and cyclophilin proteins. Taken together, our data reveal that BN, although traditionally used to treat anxiolytic disorders can be explored as a nutraceutical to improve neuronal health as well as a therapeutic option to treat cognitive disorders.