Emerging trends in nano-bioactive-mediated mitochondria-targeted therapeutic stratagems using polysaccharides, proteins and lipidic carriers.

The emergence of new lifestyle disorders and pharmaco-resistant variants of diseases has necessitated the search for effective therapeutic moieties and approaches that could overcome the limitations in the existing treatment modalities. In this context, bioactives such as flavonoids, polyphenols, tannins, terpenoids and alkaloids have demonstrated promise in therapy owing to their ability to scavenge free radicals and modulate the mitochondrial function as well as regulate metabolic pathways. However, their clinical applicability is low owing to their poor bioavailability and aqueous solubility. The encapsulation of bioactives in nanodimensional particles has overcome these limitations to a large extent while simultaneously conferring additional advantages of improved circulation time, enhanced cell uptake and target specific release. A wide range of nanocarriers derived from biopolymers such as polysaccharides, lipids and proteins, have been explored for encapsulation of different bioactives and have reported significant improvement of the bioavailability and therapeutic efficacy of the encapsulated cargo. However, incorporation of cell-specific and mitochondria-specific elements on the nanocarriers has been relatively less explored. This review summarizes some of the recent attempts to treat different disorders using bioactives encapsulated in biopolymer nanostructures and few instances of mitochondria-specific delivery.

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.