Alleviation of memory deficit by bergenin via the regulation of reelin and Nrf-2/NF-κB pathway in transgenic mouse model

Bushra Shal, Adnan Khan, Ashraf Ullah Khan, Rahim Ullah, Gowhar Ali, Salman Ul Islam, Ihsan Ul Haq, Hussain Ali, Eun Kyoung Seo, Salman Khan

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32 Scopus citations


The present study aims to determine the neuroprotective effect of Bergenin against spatial memory deficit associated with neurodegeneration. Preliminarily, the protective effect of Bergenin was observed against H2 O2-induced oxidative stress in HT-22 and PC-12 cells. Further studies were performed in 5xFAD Tg mouse model by administering Bergenin (1, 30 and 60 mg/kg; orally), whereas Bergenin (60 mg/kg) significantly attenuated the memory deficit observed in the Y-maze and Morris water maze (MWM) test. Fourier transform-infrared (FT-IR) spectroscopy displayed restoration of lipids, proteins and their derivatives compared to the 5xFAD Tg mice group. The differential scanning calorimeter (DSC) suggested an absence of amyloid beta (Aβ) aggregation in Bergenin-treated mice. The immunohistochemistry (IHC) analysis suggested the neuroprotective effect of Bergenin by increasing Reelin signaling (Reelin/Dab-1) and attenuated Aβ (1–42) aggregation in hippocampal regions of mouse brains. Furthermore, IHC and western blot results suggested antioxidant (Keap-1/Nrf-2/HO-1), anti-inflammatory (TLR-4/NF-kB) and anti-apoptotic (Bcl-2/Bax/Caspase-3) effect of Bergenin. Moreover, a decrease in Annexin V/PI-stained hippocampal cells suggested its effect against neurodegeneration. The histopathological changes were reversed significantly by Bergenin. In addition, a remarkable increase in antioxidant level with suppression of pro-inflammatory cytokines, oxidative stress and nitric oxide production were observed in specific regions of the mouse brains.

Original languageEnglish
Article number6603
JournalInternational Journal of Molecular Sciences
Issue number12
StatePublished - 2 Jun 2021

Bibliographical note

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© 2021 by the authors. Licensee MDPI, Basel, Switzerland.


  • Alzheimer’s disease
  • Bergenin
  • Memory loss
  • Neurode-generation
  • Oxidative stress
  • Reelin signaling


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