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. At present no curative treatment is available, and research focuses on drugs for slowing disease progression or providing prophylaxis. Withania somnifera (WS) also known as ‘ashwagandha’ is used widely in Ayurvedic medicine as a nerve tonic and memory enhancer. However, there is a paucity of data on the potential neuroprotective effects of W.somnifera against β-Amyloid (1–42)-induced neuropathogenesis. In the present study, we have tested the neuroprotective effects of methanol:Chloroform (3:1) extract of ashwagandha against β-amyloid induced toxicity and HIV-1Ba-L (clade B) infection using a human neuronal SK-N-MC cell line. Our results showed that β-amyloid induced cytotoxic effects in SK-N-MC cells as shown by decreased cell growth when tested individually. Also, confocal microscopic analysis showed decreased spine density, loss of spines and decreased dendrite diameter, total dendrite and spine area in clade B infected SK-N-MC cells compared to uninfected cells. However, when ashwagandha was added to β-amyloid treated and HIV-1 infected samples, the toxic effects were neutralized. Further, the MTT cell viability assays and the peroxisome proliferator-activated receptor-γ (PPARγ) levels supported these observations indicating the neuroprotective effect of WS root extract against β-amyloid and HIV-1Ba-L (clade B) induced neuro-pathogenesis.
Highlights
Alzheimer’s disease (AD), is the most common form of senile dementia, affecting more than 15 million people worldwide [1]
Chemoprevention has been acknowledged as an important and practical strategy for the management of several disorders [32,33,34]. From this point of view, we have selected Withania somnifera (WS) known as Ashwagandha, which is in common use in Indian traditional medicine to promote cognition, including memory and extracted with a mixture of methanol: chloroform (3:1) for testing the beneficial effects on SK-N-MC, a neuronal cell line
Morphological Characteristics In both, Giemsa stained flasks (Figure 2) as well as Sulphorhodamine B (SRB) stained cells (Figure 3), the βamyloid treated cells showed cytotoxic effects with decreased cell growth compared to plain controls (Figure 2,2 and Figure 3B)
Summary
Alzheimer’s disease (AD), is the most common form of senile dementia, affecting more than 15 million people worldwide [1]. The β-amyloid cytotoxicity to neuronal cells has been identified as one of the major features in AD pathology, but the exact mechanisms involved leading to neurotoxicity still remain an enigma [7]. It has been reported that HIV persists in the brain during HAART therapy and that the local inflammatory responses to HIV in the brain could lead to increased APP production and susceptibility to amyloid deposition [14]. All these observations clearly indicate that βamyloid accumulation may be a good indicator of early neuronal (axonal) degeneration during the development of Alzheimer’s disease and during HIV induced neuronal degeneration. Good progress has been made in developing the in vitro models for studying the toxic effects of β-amyloid and related peptides in cell cultures, using central nervous system (CNS) neurons or a variety of cell lines of neural origin [15]
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