Chemical Composition, Biological Activity, and Health-Promoting Effects of Withania somnifera for Pharma-Food Industry Applications

Figure 3

Major biological activities of Withania somnifera. Anticancer effects: W. somnifera exerts anticancer effects via multiple pathways, including nuclear factor (NFK-beta) and signal transducer and activator of transcription 3 (STAT3) signaling, PI3K (phosphoinositide 3-kinase)/AKT (a serine-threonine protein kinase) and mitogen-activated protein kinase (MAPK) signaling, angiogenesis inhibition, oxidative stress induction, and p53 signaling. Melanoma cells were destroyed by withaferin A via ROS-mediated apoptosis. This process activated the mitochondrial pathway, resulting in the downregulation of Bcl-2, translocation of Bax to the mitochondrial membrane, release of cytochrome c into the cytosol, abolition of transmembrane potential, and concomitant activation of caspases 9 and 3, resulting in the downregulation of proapoptotic protein, poly (ADP-Ribose) polymerase-1 (Parp-1) and DNA fragmentation. Neuroprotection: Withania somnifera reduced blood glucose, tissue lipid peroxidation (LPO), and glutathione (GSH) levels while increasing the activities of antioxidant enzymes such as glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT). This demonstrates W. somnifera’s significant free radical scavenging activity, as well as its ability to improve nonenzymatic and enzymatic antioxidants. W. somnifera root extract and withanolide A protected isolated hippocampus cells against hypobaric hypoxia-induced memory loss and neurodegeneration in vitro by stimulating the glutathione production pathway and decreasing glutathione (GSH) concentration. Furthermore, in cortical neurons treated with amyloid beta peptide, Withanolide A promoted both axonal and dendritic change as well as synaptic repair. Antidiabetic effects: W. somnifera leaf and root extracts showed antidiabetic activity by normalizing glucose uptake in skeletal myotubes and adipocytes in a dose-dependent manner. Furthermore, it considerably attenuated levels of urine and blood glucose, glucose 6-phosphatase, and tissue glycogen levels through nonenzymatic and enzymatic antioxidant mechanisms. Antimicrobial effects: the antimicrobial effect of Withania somnifera is attributed by inhibiting acid formation, acid tolerance, biofilm formation, spore germination, and hyphae growth, which in turn is mediated through gene silencing, immunopotentiation and cytotoxicity. Cardioprotective and antistress effects: the cardioprotective and cardiotropic properties of W. somnifera are demonstrated via nuclear factor erythroid 2-related transcription factor (Nrf)-2 and by activating phase II detoxification enzymes and abrogating apoptosis. Moreover, it is capable of alleviating chronic stress induced reduction of T-cell population and upregulated Th1 cytokines, thereby ensuring better stress endurance in animals as well as humans. Anti-inflammatory and antiarthritic effects: Withania somnifera alleviated inflammation by suppressing cytokines such as interleukin- (IL-) 8 and 1, tumor necrosis factor- (TNF-) α, nitric oxide (NO), and reactive oxygen species (ROS). Furthermore, withaferin A, one of the active ingredients of W. somnifera, inhibited the expression of cell adhesion molecules, leukocyte adhesion and migration, IL-6 and TNF-a production, and NF-k activation (nuclear factor kappa-light-chain-enhancer of activated B cells). Furthermore, it inhibited the phosphorylation of p38, extracellular regulated kinases (ERK 12), and c-Jun N-terminal kinase by phorbol-12-myristate-13-acetate (PMA) (JNK).