Neuroprotective Activity of Melittin—The Main Component of Bee Venom—Against Oxidative Stress Induced by Aβ<sub>25–35</sub> in In Vitro and In Vivo Models

Melittin, a 26-amino acid peptide, is the main component of the venom of four honeybee species and exhibits neuroprotective actions. However, it is unclear how melittin ameliorates neuronal cells in oxidative stress and how it affects memory impairment in an in vivo model. We evaluated the neuroprot...

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Autores principales:	Cong Duc Nguyen, Gihyun Lee
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	bee venom BDNF beta amyloid oxidative stress neurodegeneration melittin Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/6c2059a25d72404783192adb4a14a000
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spelling	oai:doaj.org-article:6c2059a25d72404783192adb4a14a0002021-11-25T16:25:25ZNeuroprotective Activity of Melittin—The Main Component of Bee Venom—Against Oxidative Stress Induced by Aβ<sub>25–35</sub> in In Vitro and In Vivo Models10.3390/antiox101116542076-3921https://doaj.org/article/6c2059a25d72404783192adb4a14a0002021-10-01T00:00:00Zhttps://www.mdpi.com/2076-3921/10/11/1654https://doaj.org/toc/2076-3921Melittin, a 26-amino acid peptide, is the main component of the venom of four honeybee species and exhibits neuroprotective actions. However, it is unclear how melittin ameliorates neuronal cells in oxidative stress and how it affects memory impairment in an in vivo model. We evaluated the neuroprotective effect of melittin on Aβ<sub>25–35</sub>-induced neuro-oxidative stress in both in vitro HT22 cells and in vivo animal model. Melittin effectively protected against HT22 cell viability and significantly deregulated the Aβ<sub>25–35</sub>-induced overproduction of intracellular reactive oxygen species. Western blot analysis showed that melittin suppressed cell apoptosis and regulated Bax/Bcl-2 ratio, as well as the expression of proapoptotic related factors: Apoptosis-inducing factor (AIF), Calpain, Cytochrome c (CytoC), Cleaved caspase-3 (Cleacas3). Additionally, melittin enhanced the antioxidant defense pathway by regulating the nuclear translocation of nuclear factor erythroid 2-like 2 (Nrf2) thus upregulated the production of the heme oxygenase-1 (HO-1), a major cellular antioxidant enzyme combating neuronal oxidative stress. Furthermore, melittin treatment activated the Tropomyosin-related kinase receptor B (TrkB)/cAMP Response Element-Binding (CREB)/Brain-derived neurotrophic factor (BDNF), contributing to neuronal neurogenesis, and regulating the normal function of synapses in the brain. In our in vivo experiment, melittin was shown to enhance the depleted learning and memory ability, a novel finding. A mouse model with cognitive deficits induced by Aβ<sub>25–35</sub> intracerebroventricular injection was used. Melittin had dose-dependently enhanced neural-disrupted animal behavior and enhanced neurogenesis in the dentate gyrus hippocampal region. Further analysis of mouse brain tissue and serum confirmed that melittin enhanced oxidant–antioxidant balance, cholinergic system activity, and intercellular neurotrophic factors regulation, which were all negatively altered by Aβ<sub>25–35</sub>. Our study shows that melittin exerts antioxidant and neuroprotective actions against neural oxidative stress. Melittin can be a potential therapeutic agent for neurodegenerative disorders.Cong Duc NguyenGihyun LeeMDPI AGarticlebee venomBDNFbeta amyloidoxidative stressneurodegenerationmelittinTherapeutics. PharmacologyRM1-950ENAntioxidants, Vol 10, Iss 1654, p 1654 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	bee venom BDNF beta amyloid oxidative stress neurodegeneration melittin Therapeutics. Pharmacology RM1-950
spellingShingle	bee venom BDNF beta amyloid oxidative stress neurodegeneration melittin Therapeutics. Pharmacology RM1-950 Cong Duc Nguyen Gihyun Lee Neuroprotective Activity of Melittin—The Main Component of Bee Venom—Against Oxidative Stress Induced by Aβ<sub>25–35</sub> in In Vitro and In Vivo Models
description	Melittin, a 26-amino acid peptide, is the main component of the venom of four honeybee species and exhibits neuroprotective actions. However, it is unclear how melittin ameliorates neuronal cells in oxidative stress and how it affects memory impairment in an in vivo model. We evaluated the neuroprotective effect of melittin on Aβ<sub>25–35</sub>-induced neuro-oxidative stress in both in vitro HT22 cells and in vivo animal model. Melittin effectively protected against HT22 cell viability and significantly deregulated the Aβ<sub>25–35</sub>-induced overproduction of intracellular reactive oxygen species. Western blot analysis showed that melittin suppressed cell apoptosis and regulated Bax/Bcl-2 ratio, as well as the expression of proapoptotic related factors: Apoptosis-inducing factor (AIF), Calpain, Cytochrome c (CytoC), Cleaved caspase-3 (Cleacas3). Additionally, melittin enhanced the antioxidant defense pathway by regulating the nuclear translocation of nuclear factor erythroid 2-like 2 (Nrf2) thus upregulated the production of the heme oxygenase-1 (HO-1), a major cellular antioxidant enzyme combating neuronal oxidative stress. Furthermore, melittin treatment activated the Tropomyosin-related kinase receptor B (TrkB)/cAMP Response Element-Binding (CREB)/Brain-derived neurotrophic factor (BDNF), contributing to neuronal neurogenesis, and regulating the normal function of synapses in the brain. In our in vivo experiment, melittin was shown to enhance the depleted learning and memory ability, a novel finding. A mouse model with cognitive deficits induced by Aβ<sub>25–35</sub> intracerebroventricular injection was used. Melittin had dose-dependently enhanced neural-disrupted animal behavior and enhanced neurogenesis in the dentate gyrus hippocampal region. Further analysis of mouse brain tissue and serum confirmed that melittin enhanced oxidant–antioxidant balance, cholinergic system activity, and intercellular neurotrophic factors regulation, which were all negatively altered by Aβ<sub>25–35</sub>. Our study shows that melittin exerts antioxidant and neuroprotective actions against neural oxidative stress. Melittin can be a potential therapeutic agent for neurodegenerative disorders.
format	article
author	Cong Duc Nguyen Gihyun Lee
author_facet	Cong Duc Nguyen Gihyun Lee
author_sort	Cong Duc Nguyen
title	Neuroprotective Activity of Melittin—The Main Component of Bee Venom—Against Oxidative Stress Induced by Aβ<sub>25–35</sub> in In Vitro and In Vivo Models
title_short	Neuroprotective Activity of Melittin—The Main Component of Bee Venom—Against Oxidative Stress Induced by Aβ<sub>25–35</sub> in In Vitro and In Vivo Models
title_full	Neuroprotective Activity of Melittin—The Main Component of Bee Venom—Against Oxidative Stress Induced by Aβ<sub>25–35</sub> in In Vitro and In Vivo Models
title_fullStr	Neuroprotective Activity of Melittin—The Main Component of Bee Venom—Against Oxidative Stress Induced by Aβ<sub>25–35</sub> in In Vitro and In Vivo Models
title_full_unstemmed	Neuroprotective Activity of Melittin—The Main Component of Bee Venom—Against Oxidative Stress Induced by Aβ<sub>25–35</sub> in In Vitro and In Vivo Models
title_sort	neuroprotective activity of melittin—the main component of bee venom—against oxidative stress induced by aβ<sub>25–35</sub> in in vitro and in vivo models
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/6c2059a25d72404783192adb4a14a000
work_keys_str_mv	AT congducnguyen neuroprotectiveactivityofmelittinthemaincomponentofbeevenomagainstoxidativestressinducedbyabsub2535subininvitroandinvivomodels AT gihyunlee neuroprotectiveactivityofmelittinthemaincomponentofbeevenomagainstoxidativestressinducedbyabsub2535subininvitroandinvivomodels
_version_	1718413205350383616

Neuroprotective Activity of Melittin—The Main Component of Bee Venom—Against Oxidative Stress Induced by Aβ<sub>25–35</sub> in In Vitro and In Vivo Models

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