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Cynanchi atrati and Its Phenolic Constituent Sinapic Acid Target Regulator of Calcineurin 1 (RCAN1) to Control Skin Inflammation

Atopic dermatitis (AD) is a common inflammatory skin disorder, and numerous pharmacological approaches are employed to reduce symptoms. Natural products of plant-derived materials have been accepted as complementary therapy for the treatment of a wide range of inflammatory diseases. Cynanchi atrati...

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Autores principales: Kim, Seon Sook, Kim, Nam Kyoung, Seo, Su Ryeon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8868251/
https://www.ncbi.nlm.nih.gov/pubmed/35204088
http://dx.doi.org/10.3390/antiox11020205
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author Kim, Seon Sook
Kim, Nam Kyoung
Seo, Su Ryeon
author_facet Kim, Seon Sook
Kim, Nam Kyoung
Seo, Su Ryeon
author_sort Kim, Seon Sook
collection PubMed
description Atopic dermatitis (AD) is a common inflammatory skin disorder, and numerous pharmacological approaches are employed to reduce symptoms. Natural products of plant-derived materials have been accepted as complementary therapy for the treatment of a wide range of inflammatory diseases. Cynanchi atrati (CA) is an oriental medicinal herb used in the treatment of acute urinary infection, febrile diseases, and laryngopharyngitis. However, the role of CA root extract in skin inflammation such as AD has not been explored yet. In this study, we examined the possible effect of CA root extract on skin inflammation and evaluated the underlying signaling mechanism using in vitro and in vivo modeling systems. Raw264.7 macrophages were used for in vitro experiments, and an oxazolone-induced AD mouse model was used to evaluate in vivo effects. CA extract significantly inhibited the expression levels of lipopolysaccharide (LPS)-induced pro-inflammatory cytokines such as interleukin-6 (IL-6) and interleukin-1β (IL-1β) in RAW264.7 macrophages. The CA root extract mediated suppression of pro-inflammatory cytokine expression and was associated with the decreased nuclear factor kappa B (NF-κB) gene transcriptional activation. Moreover, CA root extract attenuated the in vivo expression of IL-6 and tumor necrosis factor-α (TNF-α) and ear swelling in the AD mouse models. We also observed that the inhibitory effect of CA root extract on skin inflammation was accompanied by the upregulation of calcineurin 1 (RCAN1) expression, which functions in the inflammatory pathways by suppressing NF-κB signaling. We consistently observed that the immunosuppressive effect of CA root extract in AD was significantly perturbed in the RCAN1 knockout mice. In addition, we isolated a phenolic acid compound, sinapic acid (SA), from the CA root extract and found that SA consistently exerted an immunosuppressive effect in RAW264.7 macrophages by inducing RCAN1 expression. Our results provide the first evidence that CA root extract and its phenolic acid constituent, SA, modulate NF-κB signaling pathways by inducing RCAN1 expression in the skin inflammation process. Thus, we suggest that CA root extract has a therapeutic value for the treatment of AD by targeting endogenous immune regulators.
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spelling pubmed-88682512022-02-25 Cynanchi atrati and Its Phenolic Constituent Sinapic Acid Target Regulator of Calcineurin 1 (RCAN1) to Control Skin Inflammation Kim, Seon Sook Kim, Nam Kyoung Seo, Su Ryeon Antioxidants (Basel) Article Atopic dermatitis (AD) is a common inflammatory skin disorder, and numerous pharmacological approaches are employed to reduce symptoms. Natural products of plant-derived materials have been accepted as complementary therapy for the treatment of a wide range of inflammatory diseases. Cynanchi atrati (CA) is an oriental medicinal herb used in the treatment of acute urinary infection, febrile diseases, and laryngopharyngitis. However, the role of CA root extract in skin inflammation such as AD has not been explored yet. In this study, we examined the possible effect of CA root extract on skin inflammation and evaluated the underlying signaling mechanism using in vitro and in vivo modeling systems. Raw264.7 macrophages were used for in vitro experiments, and an oxazolone-induced AD mouse model was used to evaluate in vivo effects. CA extract significantly inhibited the expression levels of lipopolysaccharide (LPS)-induced pro-inflammatory cytokines such as interleukin-6 (IL-6) and interleukin-1β (IL-1β) in RAW264.7 macrophages. The CA root extract mediated suppression of pro-inflammatory cytokine expression and was associated with the decreased nuclear factor kappa B (NF-κB) gene transcriptional activation. Moreover, CA root extract attenuated the in vivo expression of IL-6 and tumor necrosis factor-α (TNF-α) and ear swelling in the AD mouse models. We also observed that the inhibitory effect of CA root extract on skin inflammation was accompanied by the upregulation of calcineurin 1 (RCAN1) expression, which functions in the inflammatory pathways by suppressing NF-κB signaling. We consistently observed that the immunosuppressive effect of CA root extract in AD was significantly perturbed in the RCAN1 knockout mice. In addition, we isolated a phenolic acid compound, sinapic acid (SA), from the CA root extract and found that SA consistently exerted an immunosuppressive effect in RAW264.7 macrophages by inducing RCAN1 expression. Our results provide the first evidence that CA root extract and its phenolic acid constituent, SA, modulate NF-κB signaling pathways by inducing RCAN1 expression in the skin inflammation process. Thus, we suggest that CA root extract has a therapeutic value for the treatment of AD by targeting endogenous immune regulators. MDPI 2022-01-21 /pmc/articles/PMC8868251/ /pubmed/35204088 http://dx.doi.org/10.3390/antiox11020205 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
Kim, Seon Sook
Kim, Nam Kyoung
Seo, Su Ryeon
Cynanchi atrati and Its Phenolic Constituent Sinapic Acid Target Regulator of Calcineurin 1 (RCAN1) to Control Skin Inflammation
title Cynanchi atrati and Its Phenolic Constituent Sinapic Acid Target Regulator of Calcineurin 1 (RCAN1) to Control Skin Inflammation
title_full Cynanchi atrati and Its Phenolic Constituent Sinapic Acid Target Regulator of Calcineurin 1 (RCAN1) to Control Skin Inflammation
title_fullStr Cynanchi atrati and Its Phenolic Constituent Sinapic Acid Target Regulator of Calcineurin 1 (RCAN1) to Control Skin Inflammation
title_full_unstemmed Cynanchi atrati and Its Phenolic Constituent Sinapic Acid Target Regulator of Calcineurin 1 (RCAN1) to Control Skin Inflammation
title_short Cynanchi atrati and Its Phenolic Constituent Sinapic Acid Target Regulator of Calcineurin 1 (RCAN1) to Control Skin Inflammation
title_sort cynanchi atrati and its phenolic constituent sinapic acid target regulator of calcineurin 1 (rcan1) to control skin inflammation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8868251/
https://www.ncbi.nlm.nih.gov/pubmed/35204088
http://dx.doi.org/10.3390/antiox11020205
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