Pharmacological mechanism of xanthoangelol underlying Nrf-2/TRPV1 and anti-apoptotic pathway against scopolamine-induced amnesia in mice

Zunaira Syed, Bushra Shal, Aqsa Azhar, Safa Amanat, Adnan Khan, Hussain Ali, Yun Seo Kil, Eun Kyoung Seo, Salman Khan

Research output: Contribution to journalArticlepeer-review

Abstract

Alzheimer's disease (AD) is a well-known type of age-related dementia. The present study was conducted to investigate the effect of xanthoangelol against memory deficit and neurodegeneration associated with AD. Preliminarily, xanthoangelol produced neuroprotective effect against H2O2-induced HT-22 cells. Furthermore, effect of xanthoangelol against scopolamine-induced amnesia in mice was determined by intraperitoneally (i.p.) administering xanthoangelol (1, 10 and 20 mg/kg), 30 min prior to induction. Mice were administered scopolamine at a concentration of 1 mg/kg; i.p. for the induction of amnesia associated with AD. Xanthoangelol dose dependently reduced the symptoms of Alzheimer's disease as observed by the results obtained from the behavioral analysis performed using Morris water maze and Y-maze test. The immunohistochemical analysis suggested that xanthoangelol significantly improved Keap-1/Nrf-2 signaling pathway. It greatly reduced the effects of oxidative stress and showed improvement in the anti-oxidant enzyme such as GSH, GST, SOD and catalase. Additionally, xanthoangelol decreased the expression of transient receptor potential vanilloid 1 (TRPV-1), a nonselective cation channel, involved in synaptic plasticity and memory. It activated the anti-oxidants and attenuated the apoptotic (Bax/Bcl-2) pathway. Xanthoangelol also significantly attenuated the scopolamine-induced neuroinflammation by the inhibition of interleukin-1 beta (IL-1β), and tumor necrosis factor-α (TNF-α) levels. The histological analysis, showed a significant reduction in amyloid plaques by xanthoangelol. Therefore, the present study indicated that xanthoangelol has the ability to ameliorate the AD symptoms by attenuating neuroinflammation and neurodegeneration induced by scopolamine.

Original languageEnglish
Article number113073
JournalBiomedicine and Pharmacotherapy
Volume150
DOIs
StatePublished - Jun 2022

Keywords

  • Alzheimer's disease
  • Apoptosis
  • Neurodegeneration
  • Neuroprotection
  • Oxidative stress
  • Xanthoangelol

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