withanolides and Parkinson-Disease

The pathogenesis of Parkinson's disease (PD) remains unclear, and there is no disease-modifying agent for PD. Withaferin A (WA), a naturally occurring compound, has emerged as a neuroprotective agent. However, the mechanisms by which WA is neuroprotective in PD are unknown. Here we show that WA protected against loss of dopaminergic neurons, neuroinflammation, and motor deficits in MPTP-induced PD mouse models. Whole-genome deep sequencing analysis combined with Meta-analysis of human PD studies reveal that DJ1, Nrf2, and STING in substantia nigra pars compacta (SNc) are linked to anti-PD effect of WA. We found that WA activated DJ1 and Nrf2, and suppressed STING within SNc; and overexpression of STING in SNc dampened the effect of WA. Using genetically modified mice (DJ1-KO, Nrf2-KO, STING

Topics: Aged; Animals; Disease Models, Animal; Humans; Male; Mice; Nervous System Diseases; Neuroprotective Agents; NF-E2-Related Factor 2; Parkinson Disease; Transfection; Withanolides

Withania somnifera, also called 'Indian ginseng', is an important medicinal plant of the Indian subcontinent. It is widely used, singly or in combination, with other herbs against many ailments in Indian Systems of Medicine since time immemorial. Withania somnifera contains a spectrum of diverse phytochemicals enabling it to have a broad range of biological implications. In preclinical studies, it has shown anti-microbial, anti-inflammatory, anti-tumor, anti-stress, neuroprotective, cardioprotective, and anti-diabetic properties. Additionally, it has demonstrated the ability to reduce reactive oxygen species, modulate mitochondrial function, regulate apoptosis, and reduce inflammation and enhance endothelial function. In view of these pharmacologic properties, W. somnifera is a potential drug candidate to treat various clinical conditions, particularly related to the nervous system. In this review, we summarize the pharmacologic characteristics and discuss the mechanisms of action and potential therapeutic applications of the plant and its active constituents.

Topics: Alzheimer Disease; Animals; Anti-Infective Agents; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents, Phytogenic; Cardiotonic Agents; Humans; India; Inflammation; Medicine, Ayurvedic; Neuroprotective Agents; Parkinson Disease; Plants, Medicinal; Withania; Withanolides

Microorganisms in human gastrointestinal tract have profound influence on the transformation of food into metabolites which can impact human health. Along with playing crucial roles in regulating and modulating various metabolic reactions and life processes, dysbiosis of gut microbiota also affects the permeability of gut and blood-brain barrier. This increases the chance of age-related neurological disorders' like Alzheimer's and Parkinson's diseases.

Topics: Alzheimer Disease; Dysbiosis; Humans; Inflammatory Bowel Diseases; Irritable Bowel Syndrome; Molecular Docking Simulation; Neurodegenerative Diseases; Parkinson Disease; Withania; Withanolides

Topics: Animals; Cell Differentiation; Cell Line; Humans; Medicine, Ayurvedic; Mice; Muscle Cells; Parkinson Disease; Plant Extracts; Withanolides