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Neuroprotective Effects of Albizia lebbeck (L.) Benth. Leaf Extract against Glutamate-Induced Endoplasmic Reticulum Stress and Apoptosis in Human Microglial Cells

Endoplasmic reticulum (ER) stress caused by excessive glutamate in the central nervous system leads to neurodegeneration. Albizia lebbeck (L.) Benth. has been reported to possess neuroprotective properties. We aimed to investigate the effect and mechanism of A. lebbeck leaf extracts on glutamate-ind...

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Autores principales: Phoraksa, Onuma, Chimkerd, Chanika, Thiyajai, Parunya, Judprasong, Kunchit, Tuntipopipat, Siriporn, Tencomnao, Tewin, Charoenkiatkul, Somsri, Muangnoi, Chawanphat, Sukprasansap, Monruedee
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10384906/
https://www.ncbi.nlm.nih.gov/pubmed/37513900
http://dx.doi.org/10.3390/ph16070989
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author Phoraksa, Onuma
Chimkerd, Chanika
Thiyajai, Parunya
Judprasong, Kunchit
Tuntipopipat, Siriporn
Tencomnao, Tewin
Charoenkiatkul, Somsri
Muangnoi, Chawanphat
Sukprasansap, Monruedee
author_facet Phoraksa, Onuma
Chimkerd, Chanika
Thiyajai, Parunya
Judprasong, Kunchit
Tuntipopipat, Siriporn
Tencomnao, Tewin
Charoenkiatkul, Somsri
Muangnoi, Chawanphat
Sukprasansap, Monruedee
author_sort Phoraksa, Onuma
collection PubMed
description Endoplasmic reticulum (ER) stress caused by excessive glutamate in the central nervous system leads to neurodegeneration. Albizia lebbeck (L.) Benth. has been reported to possess neuroprotective properties. We aimed to investigate the effect and mechanism of A. lebbeck leaf extracts on glutamate-induced neurotoxicity and apoptosis linked to ER stress using human microglial HMC3 cells. A. lebbeck leaves were extracted using hexane (AHE), mixed solvents, and ethanol. Each different extract was evaluated for cytotoxic effects on HMC3 cells, and then non-cytotoxic concentrations of the extracts were pretreated with the cells, followed by glutamate. Our results showed that AHE treatment exhibited the highest protective effect and was thus selected for finding the mechanistic approach. AHE inhibited the specific ER stress proteins (calpain1 and caspase-12). AHE also suppressed the apoptotic proteins (Bax, cytochrome c, cleaved caspase-9, and cleaved caspase-3); however, it also increased the antiapoptotic Bcl-2 protein. Remarkably, AHE increased cellular antioxidant activities (SOD, CAT, and GPx). To support the activation of antioxidant defense and inhibition of apoptosis in our HMC3 cell model, the bioactive phytochemicals within AHE were identified by HPLC analysis. We found that AHE had high levels of carotenoids (α-carotene, β-carotene, and lutein) and flavonoids (quercetin, luteolin, and kaempferol). Our novel findings indicate that AHE can inhibit glutamate-induced neurotoxicity via ER stress and apoptosis signaling pathways by activating cellular antioxidant enzymes in HMC3 cells, suggesting a potential mechanism for neuroprotection. As such, A. lebbeck leaf might potentially represent a promising source and novel alternative approach for preventing neurodegenerative diseases.
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spelling pubmed-103849062023-07-30 Neuroprotective Effects of Albizia lebbeck (L.) Benth. Leaf Extract against Glutamate-Induced Endoplasmic Reticulum Stress and Apoptosis in Human Microglial Cells Phoraksa, Onuma Chimkerd, Chanika Thiyajai, Parunya Judprasong, Kunchit Tuntipopipat, Siriporn Tencomnao, Tewin Charoenkiatkul, Somsri Muangnoi, Chawanphat Sukprasansap, Monruedee Pharmaceuticals (Basel) Article Endoplasmic reticulum (ER) stress caused by excessive glutamate in the central nervous system leads to neurodegeneration. Albizia lebbeck (L.) Benth. has been reported to possess neuroprotective properties. We aimed to investigate the effect and mechanism of A. lebbeck leaf extracts on glutamate-induced neurotoxicity and apoptosis linked to ER stress using human microglial HMC3 cells. A. lebbeck leaves were extracted using hexane (AHE), mixed solvents, and ethanol. Each different extract was evaluated for cytotoxic effects on HMC3 cells, and then non-cytotoxic concentrations of the extracts were pretreated with the cells, followed by glutamate. Our results showed that AHE treatment exhibited the highest protective effect and was thus selected for finding the mechanistic approach. AHE inhibited the specific ER stress proteins (calpain1 and caspase-12). AHE also suppressed the apoptotic proteins (Bax, cytochrome c, cleaved caspase-9, and cleaved caspase-3); however, it also increased the antiapoptotic Bcl-2 protein. Remarkably, AHE increased cellular antioxidant activities (SOD, CAT, and GPx). To support the activation of antioxidant defense and inhibition of apoptosis in our HMC3 cell model, the bioactive phytochemicals within AHE were identified by HPLC analysis. We found that AHE had high levels of carotenoids (α-carotene, β-carotene, and lutein) and flavonoids (quercetin, luteolin, and kaempferol). Our novel findings indicate that AHE can inhibit glutamate-induced neurotoxicity via ER stress and apoptosis signaling pathways by activating cellular antioxidant enzymes in HMC3 cells, suggesting a potential mechanism for neuroprotection. As such, A. lebbeck leaf might potentially represent a promising source and novel alternative approach for preventing neurodegenerative diseases. MDPI 2023-07-10 /pmc/articles/PMC10384906/ /pubmed/37513900 http://dx.doi.org/10.3390/ph16070989 Text en © 2023 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
Phoraksa, Onuma
Chimkerd, Chanika
Thiyajai, Parunya
Judprasong, Kunchit
Tuntipopipat, Siriporn
Tencomnao, Tewin
Charoenkiatkul, Somsri
Muangnoi, Chawanphat
Sukprasansap, Monruedee
Neuroprotective Effects of Albizia lebbeck (L.) Benth. Leaf Extract against Glutamate-Induced Endoplasmic Reticulum Stress and Apoptosis in Human Microglial Cells
title Neuroprotective Effects of Albizia lebbeck (L.) Benth. Leaf Extract against Glutamate-Induced Endoplasmic Reticulum Stress and Apoptosis in Human Microglial Cells
title_full Neuroprotective Effects of Albizia lebbeck (L.) Benth. Leaf Extract against Glutamate-Induced Endoplasmic Reticulum Stress and Apoptosis in Human Microglial Cells
title_fullStr Neuroprotective Effects of Albizia lebbeck (L.) Benth. Leaf Extract against Glutamate-Induced Endoplasmic Reticulum Stress and Apoptosis in Human Microglial Cells
title_full_unstemmed Neuroprotective Effects of Albizia lebbeck (L.) Benth. Leaf Extract against Glutamate-Induced Endoplasmic Reticulum Stress and Apoptosis in Human Microglial Cells
title_short Neuroprotective Effects of Albizia lebbeck (L.) Benth. Leaf Extract against Glutamate-Induced Endoplasmic Reticulum Stress and Apoptosis in Human Microglial Cells
title_sort neuroprotective effects of albizia lebbeck (l.) benth. leaf extract against glutamate-induced endoplasmic reticulum stress and apoptosis in human microglial cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10384906/
https://www.ncbi.nlm.nih.gov/pubmed/37513900
http://dx.doi.org/10.3390/ph16070989
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