Abstract
Alzheimer's disease (AD) is characterized by progressive dysfunction of memory and higher cognitive functions with abnormal accumulation of extracellular amyloid plaques and intracellular neurofibrillary tangles throughout cortical and limbic brain regions. Withania somnifera (WS) also known as ‘ashwagandha’ (ASH) is used widely in Ayurvedic medicine as a nerve tonic and memory enhancer. However, there is paucity of data on potential neuroprotective effects of ASH against β-Amyloid (1–42) (Aβ) induced neuropathogenesis. In the present study, we have tested the neuroprotective effects of Methanol: Chloroform (3:1) extract of ASH and its constituent Withanolide A (WA) against Aβ induced toxicity, HIV-1Ba-L (clade B) infection and the effects of drugs of abuse using a human neuronal SK-N-MC cell line. Aβ when tested individually, induced cytotoxic effects in SK-N-MC cells as shown by increased trypan blue stained cells. However, when ASH was added to Aβ treated cells the toxic effects were neutralized. This observation was supported by cellular localization of Aβ, MTT formazan exocytosis, and the levels of acetylcholinesterase activity, confirming the chemopreventive or protective effects of ASH against Aβ induced toxicity. Further, the levels of MAP2 were significantly increased in cells infected with HIV-1Ba-L (clade B) as well as in cells treated with Cocaine (COC) and Methamphetamine (METH) compared with control cells. In ASH treated cells the MAP2 levels were significantly less compared to controls. Similar results were observed in combination experiments. Also, WA, a purified constituent of ASH, showed same pattern using MTT assay as a parameter. These results suggests that neuroprotective properties of ASH observed in the present study may provide some explanation for the ethnopharmacological uses of ASH in traditional medicine for cognitive and other HIV associated neurodegenerative disorders and further ASH could be a potential novel drug to reduce the brain amyloid burden and/or improve the HIV-1 associated neurocognitive impairments
Highlights
Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease affecting approximately 36 million people worldwide [1] and if the current trend continues without medical innovation, one in 85 people will be affected with AD by 2050 [2]
We have reported that Ab induced cytotoxic effects in SK-N-MC cells when tested individually, when ASH was added to Ab treated cultures, the cytotoxic effects of Ab were neutralized [24]
The root powder was extracted with a mixture of methanol: chloroform (3:1) for testing the beneficial effects on SK-N-MC, a neuronal cell line
Summary
Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease affecting approximately 36 million people worldwide [1] and if the current trend continues without medical innovation, one in 85 people will be affected with AD by 2050 [2]. A widely recognized concept about AD pathogenesis is the ‘‘amyloid hypothesis,’’ whereby augmented production and self-assembly of Ab toxic constituents begins a sequence of advancing alterations that eventually lead to neuronal degeneration [10,11,12,13]. In this hypothesis, continuous Ab toxicity associated stress activates the hyper-phosphorylation and aggregation of the microtubule-associated protein tau, resulting in neurofibrillary tangles, which are a major pathological hallmark of AD [12]. All these observations indicate that Ab accumulation may be a good indicator of early neuronal (axonal) degeneration during the development of AD and during HIV induced neuronal degeneration
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
