Folecitin isolated from hypericum oblongifolium exerts neuroprotection against lipopolysaccharide-induced neuronal synapse and memory dysfunction via p-AKT/Nrf-2/HO-1 signalling pathway

Tools

Umar Farooq, Muhammad Umar Khayam Sahibzada and Khayam Sahibzada, Muhammad Umar and Khan, Taous and Ullah, Rahim and Shahid, Muhammad and Khusro, Ameer and Seidel, Veronique and Abdellattif, Magda H. and Bin Emran, Talha (2022) Folecitin isolated from hypericum oblongifolium exerts neuroprotection against lipopolysaccharide-induced neuronal synapse and memory dysfunction via p-AKT/Nrf-2/HO-1 signalling pathway. Evidence-Based Complementary and Alternative Medicine, 2022. 9419918. ISSN 1741-427X (https://doi.org/10.1155/2022/9419918)

[thumbnail of Seidel-EBCAM-2022-Folecitin-isolated-from-hypericum-oblongifolium-exerts-neuroprotection-against-lipopolysaccharide-induced-neuronal-synapse]
Preview
 Text. Filename: Seidel_EBCAM_2022_Folecitin_isolated_from_hypericum_oblongifolium_exerts_neuroprotection_against_lipopolysaccharide_induced_neuronal_synapse.pdf
Final Published Version
License: Creative Commons Attribution 4.0 logo
Download (1MB)| Preview

Abstract

Neurodegenerative diseases, especially Alzheimer's disease (AD), are characterised with neuronal synapse and memory dysfunction, and thus, there is an urgent need to find novel therapeutic medicines that can target different pathways to restore the deficits. In this investigation, we assessed the medicinal potency of folecitin (a flavonoid isolated from Hypericum oblongifolium Wall.) against lipopolysaccharide (LPS)-induced amyloidogenic amyloid beta (Aβ) production pathway-mediated memory impairment in mice. The LPS was administered intraperitonially (i.p.) 250 μg/kg/day for 3 consecutive weeks, followed by the coadministration of folecitin (30 mg/kg/day) with LPS for the last two weeks (2nd and 3rd week). The expression of various proteins involved in synapse, neuronal death, and Aβ generation was evaluated using the Western blot approach. Results indicated that folecitin significantly decreased LPS-induced apoptotic proteins; expressed BAX, PARP-1, and caspase-3 proteins; and inhibited BACE1 that cleaves transmembrane amyloid precursor protein and the amyloidogenic Aβ production pathway. Folecitin restored both preneural and postneuronal synapse, accompanied by the improvement in memory impairment. Moreover, folecitin significantly activated endogenous antioxidant proteins Nrf-2 and HO-1 by stimulating the phosphorylation of Akt proteins. These findings indicate that folecitin might be a promising target for developing novel medication to treat neurodegenerative disorders caused by neurotoxins.

ORCID iDs

Umar Farooq, Muhammad Umar Khayam Sahibzada, Khayam Sahibzada, Muhammad Umar, Khan, Taous, Ullah, Rahim, Shahid, Muhammad, Khusro, Ameer, Seidel, Veronique ORCID logoORCID: https://orcid.org/0000-0003-3880-5261, Abdellattif, Magda H. and Bin Emran, Talha;
CORE (COnnecting REpositories)