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Cytokine. 2018 Feb;102:211-221. doi: 10.1016/j.cyto.2017.10.019. Epub 2017 Nov 3.

Multifunctional neuroprotective effect of Withanone, a compound from Withania somnifera roots in alleviating cognitive dysfunction.

Author information

1
Pharmacology Divison, Indian Institute of Integrative Medicine, Canal Road, Jammu-180001, Jammu and Kashmir State, India. Electronic address: anjali290284@yahoo.co.in.
2
Pharmacology Divison, Indian Institute of Integrative Medicine, Canal Road, Jammu-180001, Jammu and Kashmir State, India. Electronic address: sarangbani@gmail.com.
3
Natural product chemistry divison, Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi-180001, Jammu and Kashmir State, India. Electronic address: prabhu.dutt@rediffmail.com.
4
Natural product chemistry divison, Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi-180001, Jammu and Kashmir State, India. Electronic address: nksatti@rediffmail.com.
5
Natural product chemistry divison, Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi-180001, Jammu and Kashmir State, India. Electronic address: kasuri_iiim@gmail.com.
6
Natural product chemistry divison, Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi-180001, Jammu and Kashmir State, India. Electronic address: qazi_gn@gmail.com.

Abstract

Alzheimer's disease (AD) is a chronic disorder that slowly worsens and impairs the person's memory, learning, reasoning, judgment, communication and familiar tasks with loss of orientation. AD is characterized clinically by cognitive deficit and pathologically by the deposition of β amyloid plaques, neurofibrillary tangles, associated with degeneration of the cholinergic forebrain. Withanone (WS-2), a compound isolated from root extract of Withania somnifera at doses administered orally/day to wistar rats for duration of 21 days showed significant improvement in the cognitive skill by inhibiting amyloid β-42 and attenuated the elevated levels of pro-inflammatory cytokines like TNF alpha, IL-1 beta, IL-6, MCP-1, Nitric oxide, lipid peroxidation and both β- and γ- secretase enzymatic activity. Administration of WS-2 also significantly reversed the decline in acetyl choline and Glutathione (GSH) activity. None of the treatments that are available today alter the underlying causes of this terminal disease. Few preliminary clinical treatments have demonstrated that some plant medicines do ameliorate and improve memory and learning in patients with mild-to-moderate AD. WS-2 showed promise in AD treatment because of cognitive benefits and more importantly, mechanisms of action with respect to the fundamental pathophysiology of the disease, not limited to the inhibition of AChE, but also include the modification of Aβ processing, protection against oxidative stress and anti-inflammatory effects.

KEYWORDS:

Amyloid beta; Catalase; MCP-1; Withania somnifera; Withanone; β secretase

PMID:
29108796
DOI:
10.1016/j.cyto.2017.10.019

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