Carvacrol Inhibits Expression of Transient Receptor Potential Melastatin 7 Channels and Alleviates Zinc Neurotoxicity Induced by Traumatic Brain Injury

Carvacrol is a monoterpenoid phenol produced by aromatic plants such as oregano. Although the exact mechanism by which carvacrol acts has not yet been established, it appears to inhibit transient receptor potential melastatin 7 (TRPM7), which modulates the homeostasis of metal ions such as zinc and...

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Main Authors: Minwoo Lee, Song Hee Lee, Seunghyuk Choi, Bo Young Choi, Sang Won Suh
Format: Article
Language:English
Published: MDPI AG 2022-11-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/22/13840
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author Minwoo Lee
Song Hee Lee
Seunghyuk Choi
Bo Young Choi
Sang Won Suh
author_facet Minwoo Lee
Song Hee Lee
Seunghyuk Choi
Bo Young Choi
Sang Won Suh
author_sort Minwoo Lee
collection DOAJ
description Carvacrol is a monoterpenoid phenol produced by aromatic plants such as oregano. Although the exact mechanism by which carvacrol acts has not yet been established, it appears to inhibit transient receptor potential melastatin 7 (TRPM7), which modulates the homeostasis of metal ions such as zinc and calcium. Several studies have demonstrated that carvacrol has protective effects against zinc neurotoxicity after ischemia and epilepsy. However, to date, no studies have investigated the effect of carvacrol on traumatic brain injury (TBI)-induced zinc neurotoxicity. In the present study, we investigated the therapeutic potential of carvacrol for the prevention of zinc-induced neuronal death after TBI. Rats were subjected to a controlled cortical impact, and carvacrol was injected at a dose of 50 mg/kg. Histological analysis was performed at 12 h, 24 h, and 7 days after TBI. We found that carvacrol reduced TBI-induced TRPM7 over-expression and free zinc accumulation. As a result, subsequent oxidative stress, dendritic damage, and neuronal degeneration were decreased. Moreover, carvacrol not only reduced microglial activation and delayed neuronal death but also improved neurological outcomes after TBI. Taken together, these findings suggest that carvacrol administration may have therapeutic potential after TBI by preventing neuronal death through the inhibition of TRPM7 expression and alleviation of zinc neurotoxicity.
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spelling doaj.art-472ed86c26c249219f5d6302793835da2023-11-24T08:34:31ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-11-0123221384010.3390/ijms232213840Carvacrol Inhibits Expression of Transient Receptor Potential Melastatin 7 Channels and Alleviates Zinc Neurotoxicity Induced by Traumatic Brain InjuryMinwoo Lee0Song Hee Lee1Seunghyuk Choi2Bo Young Choi3Sang Won Suh4Department of Physiology, Hallym University, College of Medicine, Chuncheon 24252, KoreaDepartment of Physiology, Hallym University, College of Medicine, Chuncheon 24252, KoreaDepartment of Physiology, Hallym University, College of Medicine, Chuncheon 24252, KoreaDepartment of Physical Education, Hallym University, Chuncheon 24252, KoreaDepartment of Physiology, Hallym University, College of Medicine, Chuncheon 24252, KoreaCarvacrol is a monoterpenoid phenol produced by aromatic plants such as oregano. Although the exact mechanism by which carvacrol acts has not yet been established, it appears to inhibit transient receptor potential melastatin 7 (TRPM7), which modulates the homeostasis of metal ions such as zinc and calcium. Several studies have demonstrated that carvacrol has protective effects against zinc neurotoxicity after ischemia and epilepsy. However, to date, no studies have investigated the effect of carvacrol on traumatic brain injury (TBI)-induced zinc neurotoxicity. In the present study, we investigated the therapeutic potential of carvacrol for the prevention of zinc-induced neuronal death after TBI. Rats were subjected to a controlled cortical impact, and carvacrol was injected at a dose of 50 mg/kg. Histological analysis was performed at 12 h, 24 h, and 7 days after TBI. We found that carvacrol reduced TBI-induced TRPM7 over-expression and free zinc accumulation. As a result, subsequent oxidative stress, dendritic damage, and neuronal degeneration were decreased. Moreover, carvacrol not only reduced microglial activation and delayed neuronal death but also improved neurological outcomes after TBI. Taken together, these findings suggest that carvacrol administration may have therapeutic potential after TBI by preventing neuronal death through the inhibition of TRPM7 expression and alleviation of zinc neurotoxicity.https://www.mdpi.com/1422-0067/23/22/13840traumatic brain injuryzincneuronal deathtransient receptor potential melastatin 7carvacrol
spellingShingle Minwoo Lee
Song Hee Lee
Seunghyuk Choi
Bo Young Choi
Sang Won Suh
Carvacrol Inhibits Expression of Transient Receptor Potential Melastatin 7 Channels and Alleviates Zinc Neurotoxicity Induced by Traumatic Brain Injury
International Journal of Molecular Sciences
traumatic brain injury
zinc
neuronal death
transient receptor potential melastatin 7
carvacrol
title Carvacrol Inhibits Expression of Transient Receptor Potential Melastatin 7 Channels and Alleviates Zinc Neurotoxicity Induced by Traumatic Brain Injury
title_full Carvacrol Inhibits Expression of Transient Receptor Potential Melastatin 7 Channels and Alleviates Zinc Neurotoxicity Induced by Traumatic Brain Injury
title_fullStr Carvacrol Inhibits Expression of Transient Receptor Potential Melastatin 7 Channels and Alleviates Zinc Neurotoxicity Induced by Traumatic Brain Injury
title_full_unstemmed Carvacrol Inhibits Expression of Transient Receptor Potential Melastatin 7 Channels and Alleviates Zinc Neurotoxicity Induced by Traumatic Brain Injury
title_short Carvacrol Inhibits Expression of Transient Receptor Potential Melastatin 7 Channels and Alleviates Zinc Neurotoxicity Induced by Traumatic Brain Injury
title_sort carvacrol inhibits expression of transient receptor potential melastatin 7 channels and alleviates zinc neurotoxicity induced by traumatic brain injury
topic traumatic brain injury
zinc
neuronal death
transient receptor potential melastatin 7
carvacrol
url https://www.mdpi.com/1422-0067/23/22/13840
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