Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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
_version_ 1785110885116674048
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
work_keys_str_mv AT szokekitti pharmacologicalevaluationofnewlysynthesizedcannabidiolderivatesonh9c2cells
AT kajtarrichard pharmacologicalevaluationofnewlysynthesizedcannabidiolderivatesonh9c2cells
AT gyongyosialexandra pharmacologicalevaluationofnewlysynthesizedcannabidiolderivatesonh9c2cells
AT czompaattila pharmacologicalevaluationofnewlysynthesizedcannabidiolderivatesonh9c2cells
AT fesusadina pharmacologicalevaluationofnewlysynthesizedcannabidiolderivatesonh9c2cells
AT lorinczeszterboglarka pharmacologicalevaluationofnewlysynthesizedcannabidiolderivatesonh9c2cells
AT petrocziferencdaniel pharmacologicalevaluationofnewlysynthesizedcannabidiolderivatesonh9c2cells
AT herczeghpal pharmacologicalevaluationofnewlysynthesizedcannabidiolderivatesonh9c2cells
AT bakistvan pharmacologicalevaluationofnewlysynthesizedcannabidiolderivatesonh9c2cells
AT borbasaniko pharmacologicalevaluationofnewlysynthesizedcannabidiolderivatesonh9c2cells
AT bereczkiilona pharmacologicalevaluationofnewlysynthesizedcannabidiolderivatesonh9c2cells
AT lekliistvan pharmacologicalevaluationofnewlysynthesizedcannabidiolderivatesonh9c2cells