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Pharmacological Evaluation of Newly Synthesized Cannabidiol Derivates on H9c2 Cells
Cannabidiol (CBD) is a nonpsychoactive phytocannabinoid that can be found in Cannabis sativa and possesses numerous pharmacological effects. Due to these promising effects, CBD can be used in a wide variety of diseases, for instance cardiovascular diseases. However, CBD, like tetrahydrocannabinol (T...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10525859/ https://www.ncbi.nlm.nih.gov/pubmed/37760017 http://dx.doi.org/10.3390/antiox12091714 |
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author | Szőke, Kitti Kajtár, Richárd Gyöngyösi, Alexandra Czompa, Attila Fésüs, Adina Lőrincz, Eszter Boglárka Petróczi, Ferenc Dániel Herczegh, Pál Bak, István Borbás, Anikó Bereczki, Ilona Lekli, István |
author_facet | Szőke, Kitti Kajtár, Richárd Gyöngyösi, Alexandra Czompa, Attila Fésüs, Adina Lőrincz, Eszter Boglárka Petróczi, Ferenc Dániel Herczegh, Pál Bak, István Borbás, Anikó Bereczki, Ilona Lekli, István |
author_sort | Szőke, Kitti |
collection | PubMed |
description | Cannabidiol (CBD) is a nonpsychoactive phytocannabinoid that can be found in Cannabis sativa and possesses numerous pharmacological effects. Due to these promising effects, CBD can be used in a wide variety of diseases, for instance cardiovascular diseases. However, CBD, like tetrahydrocannabinol (THC), has low bioavailability, poor water solubility, and a variable pharmacokinetic profile, which hinders its therapeutic use. Chemical derivatization of CBD offers us potential ways to overcome these issues. We prepared three new CBD derivatives substituted on the aromatic ring by Mannich-type reactions, which have not been described so far for the modification of cannabinoids, and studied the protective effect they have on cardiomyocytes exposed to oxidative stress and hypoxia/reoxygenation (H/R) compared to the parent compound. An MTT assay was performed to determine the viability of rat cardiomyocytes treated with test compounds. Trypan blue exclusion and lactate dehydrogenase (LDH) release assays were carried out to study the effect of the new compounds in cells exposed to H(2)O(2) or hypoxia/reoxygenation (H/R). Direct antioxidant activity was evaluated by a total antioxidant capacity (TAC) assay. To study antioxidant protein levels, HO-1, SOD, catalase, and Western blot analysis were carried out. pIC(50) (the negative log of the IC(50)) values were as follows: CBD1: 4.113, CBD2: 3.995, CBD3: 4.190, and CBD: 4.671. The newly synthesized CBD derivatives prevented cell death induced by H/R, especially CBD2. CBD has the largest direct antioxidant activity. The levels of antioxidant proteins were increased differently after pretreatment with synthetic CBD derivatives and CBD. Taken together, our newly synthesized CBD derivatives are able to decrease cytotoxicity during oxidative stress and H/R. The compounds have similar or better effects than CBD on H9c2 cells. |
format | Online Article Text |
id | pubmed-10525859 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-105258592023-09-28 Pharmacological Evaluation of Newly Synthesized Cannabidiol Derivates on H9c2 Cells Szőke, Kitti Kajtár, Richárd Gyöngyösi, Alexandra Czompa, Attila Fésüs, Adina Lőrincz, Eszter Boglárka Petróczi, Ferenc Dániel Herczegh, Pál Bak, István Borbás, Anikó Bereczki, Ilona Lekli, István Antioxidants (Basel) Article Cannabidiol (CBD) is a nonpsychoactive phytocannabinoid that can be found in Cannabis sativa and possesses numerous pharmacological effects. Due to these promising effects, CBD can be used in a wide variety of diseases, for instance cardiovascular diseases. However, CBD, like tetrahydrocannabinol (THC), has low bioavailability, poor water solubility, and a variable pharmacokinetic profile, which hinders its therapeutic use. Chemical derivatization of CBD offers us potential ways to overcome these issues. We prepared three new CBD derivatives substituted on the aromatic ring by Mannich-type reactions, which have not been described so far for the modification of cannabinoids, and studied the protective effect they have on cardiomyocytes exposed to oxidative stress and hypoxia/reoxygenation (H/R) compared to the parent compound. An MTT assay was performed to determine the viability of rat cardiomyocytes treated with test compounds. Trypan blue exclusion and lactate dehydrogenase (LDH) release assays were carried out to study the effect of the new compounds in cells exposed to H(2)O(2) or hypoxia/reoxygenation (H/R). Direct antioxidant activity was evaluated by a total antioxidant capacity (TAC) assay. To study antioxidant protein levels, HO-1, SOD, catalase, and Western blot analysis were carried out. pIC(50) (the negative log of the IC(50)) values were as follows: CBD1: 4.113, CBD2: 3.995, CBD3: 4.190, and CBD: 4.671. The newly synthesized CBD derivatives prevented cell death induced by H/R, especially CBD2. CBD has the largest direct antioxidant activity. The levels of antioxidant proteins were increased differently after pretreatment with synthetic CBD derivatives and CBD. Taken together, our newly synthesized CBD derivatives are able to decrease cytotoxicity during oxidative stress and H/R. The compounds have similar or better effects than CBD on H9c2 cells. MDPI 2023-09-04 /pmc/articles/PMC10525859/ /pubmed/37760017 http://dx.doi.org/10.3390/antiox12091714 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 Szőke, Kitti Kajtár, Richárd Gyöngyösi, Alexandra Czompa, Attila Fésüs, Adina Lőrincz, Eszter Boglárka Petróczi, Ferenc Dániel Herczegh, Pál Bak, István Borbás, Anikó Bereczki, Ilona Lekli, István Pharmacological Evaluation of Newly Synthesized Cannabidiol Derivates on H9c2 Cells |
title | Pharmacological Evaluation of Newly Synthesized Cannabidiol Derivates on H9c2 Cells |
title_full | Pharmacological Evaluation of Newly Synthesized Cannabidiol Derivates on H9c2 Cells |
title_fullStr | Pharmacological Evaluation of Newly Synthesized Cannabidiol Derivates on H9c2 Cells |
title_full_unstemmed | Pharmacological Evaluation of Newly Synthesized Cannabidiol Derivates on H9c2 Cells |
title_short | Pharmacological Evaluation of Newly Synthesized Cannabidiol Derivates on H9c2 Cells |
title_sort | pharmacological evaluation of newly synthesized cannabidiol derivates on h9c2 cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10525859/ https://www.ncbi.nlm.nih.gov/pubmed/37760017 http://dx.doi.org/10.3390/antiox12091714 |
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