title: β-Amyloid1-42, HIV-1Ba-L (clade B) infection and drugs of abuse induced degeneration in human neuronal cells and protective effects of ashwagandha (Withania somnifera) and its constituent Withanolide A.
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-1(Ba-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-1(Ba-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.
authors.affiliation: Department of Immunology, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Modesto A. Maidique Campus, Miami, Florida, 33199, United States of America.
authors.forename: Kesava Rao Venkata
authors.initials: KR
authors.lastname: Kurapati
authors.affiliation: Department of Immunology, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Modesto A. Maidique Campus, Miami, Florida, 33199, United States of America.
authors.forename: Thangavel
authors.initials: T
authors.lastname: Samikkannu
authors.affiliation: Department of Immunology, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Modesto A. Maidique Campus, Miami, Florida, 33199, United States of America.
authors.forename: Venkata Subba Rao
authors.initials: VS
authors.lastname: Atluri
authors.affiliation: Human and Molecular Genetics, Herbert Wertheim College of Medicine, Florida International University, Modesto A. Maidique Campus, Miami, Florida, 33199, United States of America.
authors.forename: Elena
authors.initials: E
authors.lastname: Kaftanovskaya
authors.affiliation: Department of Immunology, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Modesto A. Maidique Campus, Miami, Florida, 33199, United States of America.
authors.forename: Adriana
authors.initials: A
authors.lastname: Yndart
authors.affiliation: Department of Immunology, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Modesto A. Maidique Campus, Miami, Florida, 33199, United States of America.
authors.forename: Madhavan P N
authors.initials: MP
authors.lastname: Nair
mesh_terms: D016229:Amyloid beta-Peptides / Q000502:physiology*; D002460:Cell Line; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D013287:Illicit Drugs / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000502:physiology*; D032341:Withania / Q000737:chemistry; D054358:Withanolides / Q000494:pharmacology*
chemical_list: C433551:3-rhamnopyranosyl(1-4)-glucopyranosyl-12-diacetoxy-20-hydroxywitha-5,24-dienolide; D016229:Amyloid beta-Peptides; D013287:Illicit Drugs; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D054358:Withanolides; C075222:amyloid beta-protein (1-42)