Cargando…

Molecular Docking Identifies 1,8-Cineole (Eucalyptol) as A Novel PPARγ Agonist That Alleviates Colon Inflammation

Inflammatory bowel disease, comprising Crohn’s disease (CD) and ulcerative colitis (UC), is often debilitating. The disease etiology is multifactorial, involving genetic susceptibility, microbial dysregulation, abnormal immune activation, and environmental factors. Currently, available drug therapie...

Descripción completa

Detalles Bibliográficos
Autores principales: Venkataraman, Balaji, Almarzooqi, Saeeda, Raj, Vishnu, Bhongade, Bhoomendra A., Patil, Rajesh B., Subramanian, Veedamali S., Attoub, Samir, Rizvi, Tahir A., Adrian, Thomas E., Subramanya, Sandeep B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10094723/
https://www.ncbi.nlm.nih.gov/pubmed/37047133
http://dx.doi.org/10.3390/ijms24076160
_version_ 1785023909886689280
author Venkataraman, Balaji
Almarzooqi, Saeeda
Raj, Vishnu
Bhongade, Bhoomendra A.
Patil, Rajesh B.
Subramanian, Veedamali S.
Attoub, Samir
Rizvi, Tahir A.
Adrian, Thomas E.
Subramanya, Sandeep B.
author_facet Venkataraman, Balaji
Almarzooqi, Saeeda
Raj, Vishnu
Bhongade, Bhoomendra A.
Patil, Rajesh B.
Subramanian, Veedamali S.
Attoub, Samir
Rizvi, Tahir A.
Adrian, Thomas E.
Subramanya, Sandeep B.
author_sort Venkataraman, Balaji
collection PubMed
description Inflammatory bowel disease, comprising Crohn’s disease (CD) and ulcerative colitis (UC), is often debilitating. The disease etiology is multifactorial, involving genetic susceptibility, microbial dysregulation, abnormal immune activation, and environmental factors. Currently, available drug therapies are associated with adverse effects when used long-term. Therefore, the search for new drug candidates to treat IBD is imperative. The peroxisome proliferator-activated receptor-γ (PPARγ) is highly expressed in the colon. PPARγ plays a vital role in regulating colonic inflammation. 1,8-cineole, also known as eucalyptol, is a monoterpene oxide present in various aromatic plants which possess potent anti-inflammatory activity. Molecular docking and dynamics studies revealed that 1,8-cineole binds to PPARγ and if it were an agonist, that would explain the anti-inflammatory effects of 1,8-cineole. Therefore, we investigated the role of 1,8-cineole in colonic inflammation, using both in vivo and in vitro experimental approaches. Dextran sodium sulfate (DSS)-induced colitis was used as the in vivo model, and tumor necrosis factor-α (TNFα)-stimulated HT-29 cells as the in vitro model. 1,8-cineole treatment significantly decreased the inflammatory response in DSS-induced colitis mice. 1,8-cineole treatment also increased nuclear factor erythroid 2-related factor 2 (Nrf2) translocation into the nucleus to induce potent antioxidant effects. 1,8-cineole also increased colonic PPARγ protein expression. Similarly, 1,8-cineole decreased proinflammatory chemokine production and increased PPARγ protein expression in TNFα-stimulated HT-29 cells. 1,8-cineole also increased PPARγ promoter activity time-dependently. Because of its potent anti-inflammatory effects, 1,8-cineole may be valuable in treating IBD.
format Online
Article
Text
id pubmed-10094723
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-100947232023-04-13 Molecular Docking Identifies 1,8-Cineole (Eucalyptol) as A Novel PPARγ Agonist That Alleviates Colon Inflammation Venkataraman, Balaji Almarzooqi, Saeeda Raj, Vishnu Bhongade, Bhoomendra A. Patil, Rajesh B. Subramanian, Veedamali S. Attoub, Samir Rizvi, Tahir A. Adrian, Thomas E. Subramanya, Sandeep B. Int J Mol Sci Article Inflammatory bowel disease, comprising Crohn’s disease (CD) and ulcerative colitis (UC), is often debilitating. The disease etiology is multifactorial, involving genetic susceptibility, microbial dysregulation, abnormal immune activation, and environmental factors. Currently, available drug therapies are associated with adverse effects when used long-term. Therefore, the search for new drug candidates to treat IBD is imperative. The peroxisome proliferator-activated receptor-γ (PPARγ) is highly expressed in the colon. PPARγ plays a vital role in regulating colonic inflammation. 1,8-cineole, also known as eucalyptol, is a monoterpene oxide present in various aromatic plants which possess potent anti-inflammatory activity. Molecular docking and dynamics studies revealed that 1,8-cineole binds to PPARγ and if it were an agonist, that would explain the anti-inflammatory effects of 1,8-cineole. Therefore, we investigated the role of 1,8-cineole in colonic inflammation, using both in vivo and in vitro experimental approaches. Dextran sodium sulfate (DSS)-induced colitis was used as the in vivo model, and tumor necrosis factor-α (TNFα)-stimulated HT-29 cells as the in vitro model. 1,8-cineole treatment significantly decreased the inflammatory response in DSS-induced colitis mice. 1,8-cineole treatment also increased nuclear factor erythroid 2-related factor 2 (Nrf2) translocation into the nucleus to induce potent antioxidant effects. 1,8-cineole also increased colonic PPARγ protein expression. Similarly, 1,8-cineole decreased proinflammatory chemokine production and increased PPARγ protein expression in TNFα-stimulated HT-29 cells. 1,8-cineole also increased PPARγ promoter activity time-dependently. Because of its potent anti-inflammatory effects, 1,8-cineole may be valuable in treating IBD. MDPI 2023-03-24 /pmc/articles/PMC10094723/ /pubmed/37047133 http://dx.doi.org/10.3390/ijms24076160 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
Venkataraman, Balaji
Almarzooqi, Saeeda
Raj, Vishnu
Bhongade, Bhoomendra A.
Patil, Rajesh B.
Subramanian, Veedamali S.
Attoub, Samir
Rizvi, Tahir A.
Adrian, Thomas E.
Subramanya, Sandeep B.
Molecular Docking Identifies 1,8-Cineole (Eucalyptol) as A Novel PPARγ Agonist That Alleviates Colon Inflammation
title Molecular Docking Identifies 1,8-Cineole (Eucalyptol) as A Novel PPARγ Agonist That Alleviates Colon Inflammation
title_full Molecular Docking Identifies 1,8-Cineole (Eucalyptol) as A Novel PPARγ Agonist That Alleviates Colon Inflammation
title_fullStr Molecular Docking Identifies 1,8-Cineole (Eucalyptol) as A Novel PPARγ Agonist That Alleviates Colon Inflammation
title_full_unstemmed Molecular Docking Identifies 1,8-Cineole (Eucalyptol) as A Novel PPARγ Agonist That Alleviates Colon Inflammation
title_short Molecular Docking Identifies 1,8-Cineole (Eucalyptol) as A Novel PPARγ Agonist That Alleviates Colon Inflammation
title_sort molecular docking identifies 1,8-cineole (eucalyptol) as a novel pparγ agonist that alleviates colon inflammation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10094723/
https://www.ncbi.nlm.nih.gov/pubmed/37047133
http://dx.doi.org/10.3390/ijms24076160
work_keys_str_mv AT venkataramanbalaji moleculardockingidentifies18cineoleeucalyptolasanovelppargagonistthatalleviatescoloninflammation
AT almarzooqisaeeda moleculardockingidentifies18cineoleeucalyptolasanovelppargagonistthatalleviatescoloninflammation
AT rajvishnu moleculardockingidentifies18cineoleeucalyptolasanovelppargagonistthatalleviatescoloninflammation
AT bhongadebhoomendraa moleculardockingidentifies18cineoleeucalyptolasanovelppargagonistthatalleviatescoloninflammation
AT patilrajeshb moleculardockingidentifies18cineoleeucalyptolasanovelppargagonistthatalleviatescoloninflammation
AT subramanianveedamalis moleculardockingidentifies18cineoleeucalyptolasanovelppargagonistthatalleviatescoloninflammation
AT attoubsamir moleculardockingidentifies18cineoleeucalyptolasanovelppargagonistthatalleviatescoloninflammation
AT rizvitahira moleculardockingidentifies18cineoleeucalyptolasanovelppargagonistthatalleviatescoloninflammation
AT adrianthomase moleculardockingidentifies18cineoleeucalyptolasanovelppargagonistthatalleviatescoloninflammation
AT subramanyasandeepb moleculardockingidentifies18cineoleeucalyptolasanovelppargagonistthatalleviatescoloninflammation