Neurodegenerative diseases and Withania somnifera (L.): An update.

ETHNOPHARMACOLOGICAL RELEVANCE: Withania somnifera (L.) Dunal also known as 'Ashwaghanda' in Sanskrit and as 'Indian Winter Cherry' in english. is an important medicinal herb in India. It is widely used in Indian systems of medicine as an adaptogen, nerve tonic, anti-stress, memory enhancer and against cognitive deficits, insomnia, anxiety, infectious diseases, infertility, rheumatoid arthritis and gout over thousands of years. Its formulations are mainly used in Unani and Ayurvedic system of medicine. It is a remarkable centuries old herbal Rasayana used to treat neuronal ailments and is known as ''Sattvic Kapha Rasayana. AIM OF THE STUDY: To review neuroprotective properties of Withania somnifera (L.)extract as well as its active constituents in neurodegenerative diseases and other neurological ailments. MATERIALS AND METHODS: The sources of information used in present article include Indian system of Medicine reports on the use of natural products, Medicinal books, research articles and scientific databases like PubMed, Google Scholar, Web of Science, Science-Direct, SciFinder, ACS Publications and Wiley Online Library. RESULTS: Research reports based largely on preclinical studies as well as few clinical trials have highlighted the neuroprotective role of Ashwagandha against many neurodegenerative diseases including Alzheimer's, Huntington's and Parkinson's disease. The protective effects of Ashwagandha were accomplished by restoring mitochondrial and endothelial function, mitigation of apoptosis, inflammation and oxidative stress mechanisms. CONCLUSION: In this review, we recapitulated neuroprotective properties of Ashwagandha extracts and/or its major constituents and discussed their mechanisms of action and potential therapeutic applications. The pre-clinical as well as clinical studies suggest the use of Withania somnifera (L.) against neurodegenerative disease. However, extensive studies are warranted to validate the use of extract or its single constituents for its clinical use.

Modulation of dietary folate with age confers selective hepatocellular epigenetic imprints through DNA methylation.

The present study has been designed to determine the effect of folate modulation (deficiency/supplementation) with aging on the promoter methylation of tumor suppressor and proto-oncogenes to understand the underlying mechanism of epigenetic alterations. Folate deficiency was induced for 3 and 5 months in weanling, young and adult groups, and after 3 months of folate deficiency, they were repleted with physiological folate (2 mg/kg diet) and folate oversupplementation (8 mg/kg diet) for another 2 months. The methylation facet in the present study revealed that the combined effect of folate deficiency and aging decreased the methylation index. Folate deficiency with age resulted in the up-regulation of proto-oncogenes (C-MYC and C-JUN) and cell cycle regulator gene Cyclin E as a result of promoter hypomethylation. However, in case of tumor suppressor genes (p53, p15ink4b and p16ink4a), the expression levels were found to be decreased at transcriptional level due to promoter hypermethylation. Upon repletion with physiological folate and folate oversupplementation, we found down-regulation of proto-oncogenes and up-regulation of tumor suppressor genes as a result of promoter hypermethylation and hypomethylation, respectively. Deregulation of these important genes due to folate deficiency may contribute toward the pathogenesis at cellular level.

Pharmacologic overview of Withania somnifera, the Indian Ginseng.

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.