Therapeutic Potential of Withania somnifera Extract for Parkinson’s Disease: Impact on Neuronal Synaptic Integrity and Hormonal Regulation

Parkinson’s Disease (PD), a multifactorial movement disorder, is neuropathologically characterized by age-dependent neurodegeneration of the dopaminergic neurons in Substantia nigra. In PD patients, the hypothalamic dysfunction results in disruption of pituitary hormone secretion. Several genetic mutations contribute to the pathogenesis and advancement of PD. Among them, synaptic protein mutations play a critical role. The treatment of PD, using L-Dopa and other classes of drugs such as dopamine agonists, monoamine oxidase inhibitors, and anticholinergic agents, provides only symptomatic relief. Long-term use of these drugs produces side effects and adds to oxidative stress by producing more free radicals, which contribute to disease progression. Synaptic reconstruction and neurite regeneration are the critical steps for the retrieval of normal brain function. So, the therapeutic approach for discovering new effective neuroprotective agents that would enable neurite regeneration and establishing functional synapses is vital. Recently, emphasis has been given to the herbal medicines and their bioactive ingredients to develop alternative therapies to PD, which could provide efficient neuroprotective support to existing drugs. Withania somnifera root extract, containing steroidal alkaloids and steroidal lactones, has shown excellent potential in PD treatment. Even though Withania somnifera offers nigrostriatal dopaminergic neuroprotection by modulating oxidative stress and apoptotic machinery, the exact mechanism of neuroprotection is yet to be elucidated. Withanolide A, one of the active compounds in Withania somnifera, facilitated the neurite outgrowth and reconstruction of synapses in PD models. Additionally, this plant extract appears to alleviate endocrine-associated modifications in PD patients. This review summarizes the major findings on the use of Withania somnifera and its biochemical influences in neuroprotection, regulating endocrine function and maintenance of synaptic integrity of neurons