Isolation, Characterization and Neuroprotective Activity of Folecitin: An In Vivo Study.

Umar Farooq,Md Sanower Hossain,Naila Raziq,Taous Khan,Shahid Ali Shah,Yousaf Ali,Raffaele Capasso,Rahim Ullah,Muhammad Shahid

doi:10.3390/life11080825

Abstract

Neurodegenerative diseases (NDs) extend the global health burden. Consumption of alcohol as well as maternal exposure to ethanol can damage several neuronal functions and cause cognition and behavioral abnormalities. Ethanol induces oxidative stress that is linked to the development of NDs. Treatment options for NDs are yet scarce, and natural product-based treatments could facilitate ND management since plants possess plenty of bioactive metabolites, including flavonoids, which typically demonstrate antioxidant and anti-inflammatory properties. Hypericum oblongifolium is an important traditional medicinal plant used for hepatitis, gastric ulcer, external wounds, and other gastrointestinal disorders. However, it also possesses multiple bioactive compounds and antioxidant properties, but the evaluation of isolated pure compounds for neuroprotective efficacy has not been done yet. Therefore, in the current study, we aim to isolate and characterize the bioactive flavonoid folecitin and evaluate its neuroprotective activity against ethanol-induced oxidative-stress-mediated neurodegeneration in the hippocampus of postnatal day 7 (PND-7) rat pups. A single dose of ethanol (5 g/kg body weight) was intraperitoneally administered after the birth of rat pups on PND-7. This caused oxidative stress accompanied by the activation of phosphorylated-c-Jun N-terminal kinase (p-JNK), nod-like receptor family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein (ASC), and cysteine-aspartic acid protease-1 (caspase-1) proteins to form a complex called the NLRP3-inflammasome, which converts pro-interleukin 1 beta (IL-1B) to activate IL-1B and induce widespread neuroinflammation and neurodegeneration. In contrast, co-administration of folecitin (30 mg/kg body weight) reduced ethanol-induced oxidative stress, inhibited p-JNK, and deactivated the NLRP3-inflammasome complex. Furthermore, folecitin administration reduced neuroinflammatory and neurodegenerative protein markers, including decreased caspase-3, BCL-2-associated X protein (BAX), B cell CLL/lymphoma 2 (BCL-2), and poly (ADP-ribose) polymerase-1 (PARP-1) expression in the immature rat brain. These findings conclude that folecitin is a flavone compound, and it might be a novel, natural and safe agent to curb oxidative stress and its downstream harmful effects, including inflammasome activation, neuroinflammation, and neurodegeneration. Further evaluation in a dose-dependent manner would be worth it in order to find a suitable dose regimen for NDs.

Highlights

One of the common and growing global health burdens, in the elderly, is neurodegenerative diseases (NDs) that inexorably progress to severe disability and death
Chronic consumption of alcohol induces the development of NDs as it changes many biochemical and physiological actions in the central nervous system (CNS), of which some alterations pertain to specific neurotransmitter system changes and intricate signaling pathways [2]
Because of oxidative stress (OXS), high ethanol consumption involves the depletion of beneficial glutathione (GSH) levels and the elevation of harmful malondialdehyde, hydroxyl-ethyl radical, and hydroxynonenal protein adducts, resulting in serious cell and tissue malfunction and the progression of neuroinflammation, which can be the cause of NDs [7]

Summary

Introduction

One of the common and growing global health burdens, in the elderly, is neurodegenerative diseases (NDs) that inexorably progress to severe disability and death. NDs are linked with other risk factors such as the presence of the ApoE e4 allele, cerebrovascular diseases, hyperlipidemia, smoking, diabetes, obesity, and traumatic brain injury [1]. These risk factors impose additional health and economic burden. Among many established mechanisms of alcohol-induced NDs, oxidative stress has received much more attention in the last few years due to excessive ethanol ingestion producing an increasing amount of reactive oxygen species (ROS) and, to a lesser extent, reactive nitrogen species (RNS); it suppresses antioxidant defense mechanisms, which inactivate the ROS system, thereby resulting in oxidative stress (OXS) and/or nitrosative stress (NSS) [3,5,6]. Ethanol smoothly overcomes the blood–brain barrier and induces

Objectives

Methods

Discussion

Conclusion