Torilin Inhibits Inflammation by Limiting TAK1-Mediated MAP Kinase and NF-κB Activation.

Abstract

Torilin, a sesquiterpene isolated from the fruits of Torilis japonica, has shown antimicrobial, anticancer, and anti-inflammatory properties. However, data on the mechanism of torilin action against inflammation is limited. This study aimed at determining the anti-inflammatory property of torilin in LPS-induced inflammation using in vitro model of inflammation. We examined torilin's effect on expression levels of inflammatory mediators and cytokines in LPS-stimulated RAW 264.7 macrophages. The involvement of NF-kB and AP-1, MAP kinases, and adaptor proteins were assessed. Torilin strongly inhibited LPS-induced NO release, iNOS, PGE2, COX-2, NF-α, IL-1β, IL-6, and GM-CSF gene and protein expressions. In addition, MAPKs were also suppressed by torilin pretreatment. Involvement of ERK1/2, P38MAPK, and JNK1/2 was further confirmed by PD98059, SB203580, and SP600125 mediated suppression of iNOS and COX-2 proteins. Furthermore, torilin attenuated NF-kB and AP-1 translocation, DNA binding, and reporter gene transcription. Interestingly, torilin inhibited TAK1 kinase activation with the subsequent suppression of MAPK-mediated JNK, p38, ERK1/2, and AP-1 (ATF-2 and c-jun) activation and IKK-mediated I-κBα degradation, p65/p50 activation, and translocation. Together, the results revealed the suppression of NF-κB and AP-1 regulated inflammatory mediator and cytokine expressions, suggesting the test compound's potential as a candidate anti-inflammatory agent.

• Authors: Mehari Endale, Tae-Hwan Kim, Yi-Seong Kwak, Na-Mi Kim, Seung-Hyung Kim, Jae Youl Cho, Bong-Sik Yun, Man-Hee Rhee
• Journal: Mediators of inflammation (Mediators Inflamm) Vol. 2017 Pg. 7250968 ( 2017) ISSN: 1466-1861 [Electronic] United States
• PMID: 28316375 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents
• Interleukin-1beta
• Interleukin-6
• NF-kappa B
• Sesquiterpenes, Guaiane
• Granulocyte-Macrophage Colony-Stimulating Factor
• Cyclooxygenase 2
• Mitogen-Activated Protein Kinases
• MAP Kinase Kinase Kinases
• MAP kinase kinase kinase 7
• torilin

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Cyclooxygenase 2 (metabolism)
• Granulocyte-Macrophage Colony-Stimulating Factor (metabolism)
• Inflammation (metabolism)
• Interleukin-1beta (metabolism)
• Interleukin-6 (metabolism)
• MAP Kinase Kinase Kinases (metabolism)
• Macrophages (drug effects, metabolism)
• Mice
• Mitogen-Activated Protein Kinases (metabolism)
• NF-kappa B (metabolism)
• RAW 264.7 Cells
• Sesquiterpenes, Guaiane (pharmacology)
• Signal Transduction (drug effects)