Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Neuroprotective Efficacy of Folecitin From Hypericum Oblongifolium Against LPS-Induced Oxidative Stress, Neurodegeneration, and Memory Dysfunction

Version 1 : Received: 19 June 2021 / Approved: 23 June 2021 / Online: 23 June 2021 (11:25:28 CEST)

How to cite: Farooq, U.; Shah, S.A.; Khan, T.; Ullah, R.; Raziq, N.; Shahid, M.; Khusro, A.; Sahibzada, M.U.K.; Seidel, V.; Alkhedaide, A.; Batiha, G.E.; Koirala, N. Neuroprotective Efficacy of Folecitin From Hypericum Oblongifolium Against LPS-Induced Oxidative Stress, Neurodegeneration, and Memory Dysfunction. Preprints 2021, 2021060576. https://doi.org/10.20944/preprints202106.0576.v1 Farooq, U.; Shah, S.A.; Khan, T.; Ullah, R.; Raziq, N.; Shahid, M.; Khusro, A.; Sahibzada, M.U.K.; Seidel, V.; Alkhedaide, A.; Batiha, G.E.; Koirala, N. Neuroprotective Efficacy of Folecitin From Hypericum Oblongifolium Against LPS-Induced Oxidative Stress, Neurodegeneration, and Memory Dysfunction. Preprints 2021, 2021060576. https://doi.org/10.20944/preprints202106.0576.v1

Abstract

Neurological disorders, such as amyotrophic lateral sclerosis, Parkinson’s disease, and Alzheimer’s disease, are commonly associated with persistent neuro-inflammation, and there is an urgent need to discover new therapeutic agents that may target the various pathways involved in neurodegeneration. In this study, we investigated the therapeutic potential of folecitin, a flavonoid isolated from Hypericum oblongifolium, against lipopolysaccharide (LPS)-induced oxidative stress associated with neurodegeneration, amyloidogenic Aβ production pathway, and memory dysfunction in mice. LPS was administered i.p. at 250 µg/kg/day for 3 weeks, followed by the administration of folecitin at a dose of 30 mg/kg/day for the last two weeks. A Western blot technique was used to assess the expression of different proteins involved in oxidative stress, neurodegeneration, and neuronal synapse. Results indicated that folecitin significantly reduced LPS-induced apoptotic neurodegeneration, including the expression of BAX, Caspase-3, and PARP-1 proteins, inhibited BACE1, and the amyloidogenic Aβ production pathway. Folecitin improved both pre- and post-neuronal synapse, as well as memory dysfunction. Furthermore, folecitin significantly activated endogenous antioxidant proteins such as Nrf-2 and HO-1 via stimulating the phosphorylation of Akt proteins. These findings suggest that folecitin may be a suitable lead to design new drugs for neurotoxin-triggered neurodegenerative disorders.

Keywords

Hypericum oblongifolium; Alzheimer’s disease; Folecitin; Memory impairment; Neurodegenerative disease; Neuroprotection

Subject

Chemistry and Materials Science, Analytical Chemistry

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