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Anti-Inflammatory Mechanism of An Alkaloid Rutaecarpine in LTA-Stimulated RAW 264.7 Cells: Pivotal Role on NF-κB and ERK/p38 Signaling Molecules

Lipoteichoic acid (LTA) is a key cell wall component and virulence factor of Gram-positive bacteria. LTA contributes a major role in infection and it mediates inflammatory responses in the host. Rutaecarpine, an indolopyridoquinazolinone alkaloid isolated from Evodia rutaecarpa, has shown a variety...

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Autores principales: Jayakumar, Thanasekaran, Yang, Chun-Ming, Yen, Ting-Lin, Hsu, Chia-Yuan, Sheu, Joen-Rong, Hsia, Chih-Wei, Manubolu, Manjunath, Huang, Wei-Chieh, Hsieh, Cheng-Ying, Hsia, Chih-Hsuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9180084/
https://www.ncbi.nlm.nih.gov/pubmed/35682568
http://dx.doi.org/10.3390/ijms23115889
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author Jayakumar, Thanasekaran
Yang, Chun-Ming
Yen, Ting-Lin
Hsu, Chia-Yuan
Sheu, Joen-Rong
Hsia, Chih-Wei
Manubolu, Manjunath
Huang, Wei-Chieh
Hsieh, Cheng-Ying
Hsia, Chih-Hsuan
author_facet Jayakumar, Thanasekaran
Yang, Chun-Ming
Yen, Ting-Lin
Hsu, Chia-Yuan
Sheu, Joen-Rong
Hsia, Chih-Wei
Manubolu, Manjunath
Huang, Wei-Chieh
Hsieh, Cheng-Ying
Hsia, Chih-Hsuan
author_sort Jayakumar, Thanasekaran
collection PubMed
description Lipoteichoic acid (LTA) is a key cell wall component and virulence factor of Gram-positive bacteria. LTA contributes a major role in infection and it mediates inflammatory responses in the host. Rutaecarpine, an indolopyridoquinazolinone alkaloid isolated from Evodia rutaecarpa, has shown a variety of fascinating biological properties such as anti-thrombotic, anticancer, anti-obesity and thermoregulatory, vasorelaxing activity. It has also potent effects on the cardiovascular and endocrine systems. Herein, we investigated rutaecarpine’s (Rut) anti-inflammatory effects in LTA-stimulated RAW macrophage cells. The Western blot and spectrophotometric results revealed that Rut inhibited the production of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and interleukin (IL)-1β in the LTA-induced macrophage cells. Successively, our mechanistic studies publicized that Rut inhibited LTA-induced phosphorylation of mitogen-activated protein kinase (MAPK) including the extracellular signal-regulated kinase (ERK), and p38, but not c-Jun NH2-terminal kinase (JNK). In addition, the respective Western blot and confocal image analyses exhibited that Rut reserved nuclear transcription factor kappa-B (NF-κB) by hindering inhibitor of nuclear factor κB-α (IκBα) and NF-κB p65 phosphorylation and p65 nuclear translocation. These results indicate that Rut exhibits its anti-inflammatory effects mainly through attenuating NF-κB and ERK/p38 signaling pathways. Overall, this result suggests that Rut could be a potential therapeutic agent for the treatment of Gram-positive bacteria induced inflammatory diseases.
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spelling pubmed-91800842022-06-10 Anti-Inflammatory Mechanism of An Alkaloid Rutaecarpine in LTA-Stimulated RAW 264.7 Cells: Pivotal Role on NF-κB and ERK/p38 Signaling Molecules Jayakumar, Thanasekaran Yang, Chun-Ming Yen, Ting-Lin Hsu, Chia-Yuan Sheu, Joen-Rong Hsia, Chih-Wei Manubolu, Manjunath Huang, Wei-Chieh Hsieh, Cheng-Ying Hsia, Chih-Hsuan Int J Mol Sci Article Lipoteichoic acid (LTA) is a key cell wall component and virulence factor of Gram-positive bacteria. LTA contributes a major role in infection and it mediates inflammatory responses in the host. Rutaecarpine, an indolopyridoquinazolinone alkaloid isolated from Evodia rutaecarpa, has shown a variety of fascinating biological properties such as anti-thrombotic, anticancer, anti-obesity and thermoregulatory, vasorelaxing activity. It has also potent effects on the cardiovascular and endocrine systems. Herein, we investigated rutaecarpine’s (Rut) anti-inflammatory effects in LTA-stimulated RAW macrophage cells. The Western blot and spectrophotometric results revealed that Rut inhibited the production of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and interleukin (IL)-1β in the LTA-induced macrophage cells. Successively, our mechanistic studies publicized that Rut inhibited LTA-induced phosphorylation of mitogen-activated protein kinase (MAPK) including the extracellular signal-regulated kinase (ERK), and p38, but not c-Jun NH2-terminal kinase (JNK). In addition, the respective Western blot and confocal image analyses exhibited that Rut reserved nuclear transcription factor kappa-B (NF-κB) by hindering inhibitor of nuclear factor κB-α (IκBα) and NF-κB p65 phosphorylation and p65 nuclear translocation. These results indicate that Rut exhibits its anti-inflammatory effects mainly through attenuating NF-κB and ERK/p38 signaling pathways. Overall, this result suggests that Rut could be a potential therapeutic agent for the treatment of Gram-positive bacteria induced inflammatory diseases. MDPI 2022-05-24 /pmc/articles/PMC9180084/ /pubmed/35682568 http://dx.doi.org/10.3390/ijms23115889 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
Jayakumar, Thanasekaran
Yang, Chun-Ming
Yen, Ting-Lin
Hsu, Chia-Yuan
Sheu, Joen-Rong
Hsia, Chih-Wei
Manubolu, Manjunath
Huang, Wei-Chieh
Hsieh, Cheng-Ying
Hsia, Chih-Hsuan
Anti-Inflammatory Mechanism of An Alkaloid Rutaecarpine in LTA-Stimulated RAW 264.7 Cells: Pivotal Role on NF-κB and ERK/p38 Signaling Molecules
title Anti-Inflammatory Mechanism of An Alkaloid Rutaecarpine in LTA-Stimulated RAW 264.7 Cells: Pivotal Role on NF-κB and ERK/p38 Signaling Molecules
title_full Anti-Inflammatory Mechanism of An Alkaloid Rutaecarpine in LTA-Stimulated RAW 264.7 Cells: Pivotal Role on NF-κB and ERK/p38 Signaling Molecules
title_fullStr Anti-Inflammatory Mechanism of An Alkaloid Rutaecarpine in LTA-Stimulated RAW 264.7 Cells: Pivotal Role on NF-κB and ERK/p38 Signaling Molecules
title_full_unstemmed Anti-Inflammatory Mechanism of An Alkaloid Rutaecarpine in LTA-Stimulated RAW 264.7 Cells: Pivotal Role on NF-κB and ERK/p38 Signaling Molecules
title_short Anti-Inflammatory Mechanism of An Alkaloid Rutaecarpine in LTA-Stimulated RAW 264.7 Cells: Pivotal Role on NF-κB and ERK/p38 Signaling Molecules
title_sort anti-inflammatory mechanism of an alkaloid rutaecarpine in lta-stimulated raw 264.7 cells: pivotal role on nf-κb and erk/p38 signaling molecules
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9180084/
https://www.ncbi.nlm.nih.gov/pubmed/35682568
http://dx.doi.org/10.3390/ijms23115889
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