Therapeutic effects of ashwagandha in brain aging and clock dysfunction

Abstract

The master pacemaker, the suprachiasmatic nucleus (SCN), containing light-entrained circadian clock orchestring mammalian circadian rhythms in physiology and behavior is located in hypothalamus. SCN possessing core circadian machinery genes regulates the synthesis and release of melatonin (messanger of darkness) from the pineal gland via multisynaptic pathway. The decline in endogenous levels of this multitasking molecule with aging is associated with circadian dysfunction, neurodegeneration and brain aging as well as alterations in the endogenous defense and survival mechanisms. The age-related neurodegenerative disorders in the elderly have increased dramatically parallel to increase in longevity limiting quality of life. This is linked to need for development of effective therapeutic agents for healthy aging. Herbal extracts or formulations have been in use since ancient cultures involving herbal medicines which are of greater scientific interest as have been demonstrated to be capable of treating disease and improving health often without any significant side effects. Ashwagandha, Withania somnifera (WS), has been reported to have biologically active constituents such as alkaloids, steroidal compounds, glycowithanolides etc. Having anti-oxidative, anti-aging and antiinflammatory properties. The studies in our laboratory have revealed the therapeutic and adaptogenic potential of hydroalcoholic leaf extract of WS on age induced alterations in various clock gene expression and its modulators. This chapter is aimed to summarize the current knowledge on the changes of the circadian system in advanced age and the therapeutic effects of WS on brain aging and clock dysfunctions.