No abstract

Oxidative stress is the state of imbalance between the production of reactive oxygen species (free radicals) in the biological system and the ability of the body to detoxify them resulting in increased accumulation of free radicals in the cells. This stress leads to weakening of the immune system thus leading to higher susceptibility to other infections as well. This also includes the weakening of the respiratory tract leading to increased susceptibility of viral infections as in the case of COVID-19. Treatment for any kind of abnormality requires the identification of the key target proteins and pathways that are being altered. Withania somnifera is being used in the traditional medicinal system to improve health and longevity thus creating a sense of mental as well as physical well being. The present study utilises network pharmacological approach to predict the potential oxidative stress targets of the three major withanolides: withanolide A, withaferin A and withanone. Primarily, the targets of the individual withanolides were obtained from the Swiss target and DIGEP-pred databases and the GO terms and lead hits related to oxidative stress were retrieved from AMIGO2 database. Totally 40 correlative hits were obtained as anti stress targets of the withanolides, which were subjected to functional enrichment and protein–protein interaction analysis to study the enriched pathways underlying oxidative stress response. Further the eleven crucial targets of the four selected pathways were analysed using molecular docking analysis. A total of forty protein hits were obtained as oxidative stress targets of the withanolides. Further, the pathway enrichment of these forty target genes showed the AGE RAGE signalling pathway as highly enriched pathway. Therefore, the AGE RAGE signalling pathway along with its underlying pathways namely MAPK signalling pathway, FOXO pathway and PI3-AKT pathway were chosen among all the other enriched pathways. Further the molecular docking analysis of the eleven target proteins falling under these four pathways showed good docking scores of the withanolides with all the eleven targets with the highest interaction against BCL2.  From the above study, the biological targets and associated pathways of the withanolides have been retrieved.  Thus the in silico approach undertaken in this study explores the role of the key withanolides in the antioxidant potential of the traditional medicinal plant Withania somnifera.

Adaptogens are natural (herbs) or synthetic compounds (levamisole) used to maintain stability in human body. The plant based adaptogens were mainly used to enhance the physical endurance and metal health of patients. However, adaptogens are widely studied for their ability to protect and cope up the body against physical, chemical and biological stress and related diseases. Panax ginseng and Withania somnifera are natural adaptogens, used to attenuate stress & related disorders without increasing oxygen consumption. This review deals with a detailed description of adaptogenic potential of Panax ginseng and Withania somnifera in improving human health. It also focuses on the similarity and mechanism of action of Panax ginseng and Withania somnifera as adaptogens on human stress induced disorders.