Cargando…
Nrf2/HO-1 Signaling Stimulation through Acetyl-11-Keto-Beta-Boswellic Acid (AKBA) Provides Neuroprotection in Ethidium Bromide-Induced Experimental Model of Multiple Sclerosis
Multiple sclerosis (MS) is a severe immune-mediated neurological disease characterized by neuroinflammation, demyelination, and axonal degeneration in the central nervous system (CNS). This is frequently linked to motor abnormalities and cognitive impairments. The pathophysiological hallmarks of MS...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9331916/ https://www.ncbi.nlm.nih.gov/pubmed/35893061 http://dx.doi.org/10.3390/genes13081324 |
_version_ | 1784758519759634432 |
---|---|
author | Upadhayay, Shubham Mehan, Sidharth Prajapati, Aradhana Sethi, Pranshul Suri, Manisha Zawawi, Ayat Almashjary, Majed N. Tabrez, Shams |
author_facet | Upadhayay, Shubham Mehan, Sidharth Prajapati, Aradhana Sethi, Pranshul Suri, Manisha Zawawi, Ayat Almashjary, Majed N. Tabrez, Shams |
author_sort | Upadhayay, Shubham |
collection | PubMed |
description | Multiple sclerosis (MS) is a severe immune-mediated neurological disease characterized by neuroinflammation, demyelination, and axonal degeneration in the central nervous system (CNS). This is frequently linked to motor abnormalities and cognitive impairments. The pathophysiological hallmarks of MS include inflammatory demyelination, axonal injury, white matter degeneration, and the development of CNS lesions that result in severe neuronal degeneration. Several studies suggested downregulation of nuclear factor erythroid-2-related factor-2 (Nrf2)/Heme oxygenase-1 (HO-1) signaling is a causative factor for MS pathogenesis. Acetyl-11-keto-β-boswellic acid (AKBA) is an active pentacyclictriterpenoid obtained from Boswellia serrata, possessing antioxidant and anti-inflammatory properties. The present study explores the protective potential of AKBA on behavioral, molecular, neurochemical, and gross pathological abnormalitiesandhistopathological alterations by H&E and LFB staining techniques in an experimental model of multiple sclerosis, emphasizing the increase inNrf2/HO-1 levels in the brain. Moreover, we also examine the effect of AKBA on the intensity of myelin basic protein (MBP) in CSF and rat brain homogenate. Specific apoptotic markers (Bcl-2, Bax, andcaspase-3) were also estimated in rat brain homogenate. Neuro behavioralabnormalities in rats were examined using an actophotometer, rotarod test, beam crossing task (BCT),and Morris water maze (MWM). AKBA 50 mg/kg and 100 mg/kg were given orally from day 8 to 35 to alleviate MS symptoms in the EB-injected rats. Furthermore, cellular, molecular, neurotransmitter, neuroinflammatory cytokine, and oxidative stress markers in rat whole brain homogenate, blood plasma, and cerebral spinal fluid were investigated. This study shows that AKBA upregulates the level of antioxidant proteins such as Nrf2 and HO-1 in the rat brain. AKBA restores altered neurochemical levels, potentially preventing gross pathological abnormalities during MS progression. |
format | Online Article Text |
id | pubmed-9331916 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-93319162022-07-29 Nrf2/HO-1 Signaling Stimulation through Acetyl-11-Keto-Beta-Boswellic Acid (AKBA) Provides Neuroprotection in Ethidium Bromide-Induced Experimental Model of Multiple Sclerosis Upadhayay, Shubham Mehan, Sidharth Prajapati, Aradhana Sethi, Pranshul Suri, Manisha Zawawi, Ayat Almashjary, Majed N. Tabrez, Shams Genes (Basel) Article Multiple sclerosis (MS) is a severe immune-mediated neurological disease characterized by neuroinflammation, demyelination, and axonal degeneration in the central nervous system (CNS). This is frequently linked to motor abnormalities and cognitive impairments. The pathophysiological hallmarks of MS include inflammatory demyelination, axonal injury, white matter degeneration, and the development of CNS lesions that result in severe neuronal degeneration. Several studies suggested downregulation of nuclear factor erythroid-2-related factor-2 (Nrf2)/Heme oxygenase-1 (HO-1) signaling is a causative factor for MS pathogenesis. Acetyl-11-keto-β-boswellic acid (AKBA) is an active pentacyclictriterpenoid obtained from Boswellia serrata, possessing antioxidant and anti-inflammatory properties. The present study explores the protective potential of AKBA on behavioral, molecular, neurochemical, and gross pathological abnormalitiesandhistopathological alterations by H&E and LFB staining techniques in an experimental model of multiple sclerosis, emphasizing the increase inNrf2/HO-1 levels in the brain. Moreover, we also examine the effect of AKBA on the intensity of myelin basic protein (MBP) in CSF and rat brain homogenate. Specific apoptotic markers (Bcl-2, Bax, andcaspase-3) were also estimated in rat brain homogenate. Neuro behavioralabnormalities in rats were examined using an actophotometer, rotarod test, beam crossing task (BCT),and Morris water maze (MWM). AKBA 50 mg/kg and 100 mg/kg were given orally from day 8 to 35 to alleviate MS symptoms in the EB-injected rats. Furthermore, cellular, molecular, neurotransmitter, neuroinflammatory cytokine, and oxidative stress markers in rat whole brain homogenate, blood plasma, and cerebral spinal fluid were investigated. This study shows that AKBA upregulates the level of antioxidant proteins such as Nrf2 and HO-1 in the rat brain. AKBA restores altered neurochemical levels, potentially preventing gross pathological abnormalities during MS progression. MDPI 2022-07-25 /pmc/articles/PMC9331916/ /pubmed/35893061 http://dx.doi.org/10.3390/genes13081324 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Upadhayay, Shubham Mehan, Sidharth Prajapati, Aradhana Sethi, Pranshul Suri, Manisha Zawawi, Ayat Almashjary, Majed N. Tabrez, Shams Nrf2/HO-1 Signaling Stimulation through Acetyl-11-Keto-Beta-Boswellic Acid (AKBA) Provides Neuroprotection in Ethidium Bromide-Induced Experimental Model of Multiple Sclerosis |
title | Nrf2/HO-1 Signaling Stimulation through Acetyl-11-Keto-Beta-Boswellic Acid (AKBA) Provides Neuroprotection in Ethidium Bromide-Induced Experimental Model of Multiple Sclerosis |
title_full | Nrf2/HO-1 Signaling Stimulation through Acetyl-11-Keto-Beta-Boswellic Acid (AKBA) Provides Neuroprotection in Ethidium Bromide-Induced Experimental Model of Multiple Sclerosis |
title_fullStr | Nrf2/HO-1 Signaling Stimulation through Acetyl-11-Keto-Beta-Boswellic Acid (AKBA) Provides Neuroprotection in Ethidium Bromide-Induced Experimental Model of Multiple Sclerosis |
title_full_unstemmed | Nrf2/HO-1 Signaling Stimulation through Acetyl-11-Keto-Beta-Boswellic Acid (AKBA) Provides Neuroprotection in Ethidium Bromide-Induced Experimental Model of Multiple Sclerosis |
title_short | Nrf2/HO-1 Signaling Stimulation through Acetyl-11-Keto-Beta-Boswellic Acid (AKBA) Provides Neuroprotection in Ethidium Bromide-Induced Experimental Model of Multiple Sclerosis |
title_sort | nrf2/ho-1 signaling stimulation through acetyl-11-keto-beta-boswellic acid (akba) provides neuroprotection in ethidium bromide-induced experimental model of multiple sclerosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9331916/ https://www.ncbi.nlm.nih.gov/pubmed/35893061 http://dx.doi.org/10.3390/genes13081324 |
work_keys_str_mv | AT upadhayayshubham nrf2ho1signalingstimulationthroughacetyl11ketobetaboswellicacidakbaprovidesneuroprotectioninethidiumbromideinducedexperimentalmodelofmultiplesclerosis AT mehansidharth nrf2ho1signalingstimulationthroughacetyl11ketobetaboswellicacidakbaprovidesneuroprotectioninethidiumbromideinducedexperimentalmodelofmultiplesclerosis AT prajapatiaradhana nrf2ho1signalingstimulationthroughacetyl11ketobetaboswellicacidakbaprovidesneuroprotectioninethidiumbromideinducedexperimentalmodelofmultiplesclerosis AT sethipranshul nrf2ho1signalingstimulationthroughacetyl11ketobetaboswellicacidakbaprovidesneuroprotectioninethidiumbromideinducedexperimentalmodelofmultiplesclerosis AT surimanisha nrf2ho1signalingstimulationthroughacetyl11ketobetaboswellicacidakbaprovidesneuroprotectioninethidiumbromideinducedexperimentalmodelofmultiplesclerosis AT zawawiayat nrf2ho1signalingstimulationthroughacetyl11ketobetaboswellicacidakbaprovidesneuroprotectioninethidiumbromideinducedexperimentalmodelofmultiplesclerosis AT almashjarymajedn nrf2ho1signalingstimulationthroughacetyl11ketobetaboswellicacidakbaprovidesneuroprotectioninethidiumbromideinducedexperimentalmodelofmultiplesclerosis AT tabrezshams nrf2ho1signalingstimulationthroughacetyl11ketobetaboswellicacidakbaprovidesneuroprotectioninethidiumbromideinducedexperimentalmodelofmultiplesclerosis |