WITHAFERIN A: AN EXPLORATION OF TROPANE ALKALOID ASSOCIATED NEUROLOGICAL DYSFUNCTION BY CONQUERING A BETA PROTEIN
AbstractNeurological problems should be considered a major public health issue. Around 40%–70% of people exposed to HIV suffer neurological problems such as Amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), and other comparable conditions. Various neurological diseases including ALS, Alzheimer’s, and Parkinson’s disease are caused by amyloid-beta accumulation in extracellular regions of the brain. The Substantia nigra’s dopaminergic neurons have been damaged in a widespread and gradual manner. The life span of HIV-infected patients has risen during this period of antiretroviral medication, resulting in increased neurocognitive impairment in around 33% of HIV entities, mainly adults. The testimony of the A inscriptions in the CNS is the most popular sight among elderly HIV patients. ART is separated from harmful duplication, but the harmful neuronal protein (Tat) is still produced, following in facilitated A phases. Furthermore, Cocaine-like drug (COC) use has been linked to HIV-related neurocognitive issues and A excretion. Withaferin A is emitted by inducing the targeting Tat and COC, we suggest Withaferin A (WA), a contemporary bifunctional fragment that acts as a neuroprotectant in the face of A neurotoxicity. In APP-transfected plasmid SH-SY5Y cells, WA lowers secreted A and reduces neurotoxicity (SH-APP). In this research, we investigated that in the availability of HIV-1 Tat which is a neurotoxin and the abusive drug COC, A secretion is enhanced in SH-APP cells. When related to normal control SH-APP cells, Luminescence microscopy tests confirm the elevated concentrations of A40 (50 ng/ml) and COC (0.1 M) in test SH-APP cells. Lower doses of WA (0.5–2 M) considerably lower A40 levels in SH-APP cells while generating no cytotoxicity, according to the dose optimization study. WA also lowers the amount of A produced by Tat and Cocaine. As a consequence, we conclude that the presence of Tat and Cocaine promotes A aggregation, but that WA is effective in eliminating hidden A and preventing subsequent neurotoxicity. This study opens up new paths for the finding of viral contamination in brain diseases. Our findings revealed that there are new levels of medicinal competence that are incompatible with neurological disorders.
Article Information
47
5074-5086
1317 KB
177
English
IJPSR
Sonu Sharma, Vineylather *, Vikram Sharma and Chetan Ram
Amity Institute of Pharmacy, Amity University, Noida, Uttar Pradesh, India.
vlather@amity.edu
22 February 2023
05 April 2023
28 September 2023
10.13040/IJPSR.0975-8232.14(10).5074-86
01 October 2023