title: Withanone, an Active Constituent from Withania somnifera, Affords Protection Against NMDA-Induced Excitotoxicity in Neuron-Like Cells.
abstract: Withania somnifera has immense pharmacologic and clinical uses. Owing to its similar pharmacologic activity as that of Korean Ginseng tea, it is popularly called as Indian ginseng. In most cases, extracts of this plant have been evaluated against various diseases or models of disease. However, little efforts have been made to evaluate individual constituents of this plant for neurodegenerative disorders. Present study was carried out to evaluate Withanone, one of the active constituents of Withania somnifera against NMDA-induced excitotoxicity in retinoic acid, differentiated Neuro2a cells. Cells were pre-treated with 5, 10 and 20 μM doses of Withanone and then exposed to 3-mM NMDA for 1 h. MK801, a specific NMDA receptor antagonist, was used as positive control. The results indicated that NMDA induces significant death of cells by accumulation of intracellular Ca2+, generation of reactive oxygen species (ROS), loss of mitochondrial membrane potential, crashing of Bax/Bcl-2 ratio, release of cytochrome c, increased caspase expression, induction of lipid peroxidation as measured by malondialdehyde levels and cleavage of poly(ADP-ribose) polymerase-1 (Parp-1), which is indicative of DNA damage. All these parameters were attenuated with various doses of Withanone pre-treatment. These results suggest that Withanone may serve as potential neuroprotective agent.
authors.affiliation: Neuropharmacology Laboratory, CSIR-Indian Institute of Integrative Medicine, Sanat Nagar, Srinagar, India.|Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu, India.|Academy of Scientific and Innovative Research, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu, India.
authors.forename: Nawab John
authors.initials: NJ
authors.lastname: Dar
authors.affiliation: Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu, India.
authors.forename: Javeed Ahmad
authors.initials: JA
authors.lastname: Bhat
authors.affiliation: Natural Product Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu, India.
authors.forename: Naresh Kumar
authors.initials: NK
authors.lastname: Satti
authors.affiliation: Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu, India.
authors.forename: Parduman Raj
authors.initials: PR
authors.lastname: Sharma
authors.affiliation: Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu, India. ahdar@iiim.ac.in.|Academy of Scientific and Innovative Research, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu, India. ahdar@iiim.ac.in.
authors.forename: Abid
authors.initials: A
authors.lastname: Hamid
authors.affiliation: Neuropharmacology Laboratory, CSIR-Indian Institute of Integrative Medicine, Sanat Nagar, Srinagar, India. mahmad@iiim.res.in.|Academy of Scientific and Innovative Research, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu, India. mahmad@iiim.res.in.
authors.forename: Muzamil
authors.identifier: http://orcid.org/0000-0003-1066-1817
authors.initials: M
authors.lastname: Ahmad
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*; D054358:Withanolides
chemical_list: D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D016194:Receptors, N-Methyl-D-Aspartate; D014315:Triterpenes; D054358:Withanolides; D011065:Poly(ADP-ribose) Polymerases; C560597:withanone
keywords: Caspase; Cytochrome c; Glutamate; Intracellular calcium; NMDA; Parp-1; ROS; Withania somnifera; Withanone