Auraptene, a Monoterpene Coumarin, Inhibits LTA-Induced Inflammatory Mediators via Modulating NF-κB/MAPKs Signaling Pathways.

Chih-Hsuan Hsia,Wan-Jung Lu,Periyakali Saravana Bhavan,Thanasekaran Jayakumar,Manjunath Manubolu,Yi Chang,Joen-Rong Sheu,Chih-Wei Hsia,Wei-Chieh Huang,Weicheng Hu

doi:10.1155/2021/5319584

Abstract

Objective Oxidative stress-mediated inflammatory events involve in the progress of several diseases such as asthma, cancers, and multiple sclerosis. Auraptene (AU), a natural prenyloxycoumarin, possesses numerous pharmacological activities. Here, the anti-inflammatory effects of AU were investigated in lipoteichoic acid- (LTA-) induced macrophage cells (RAW 264.7). Methods The expression of cyclooxygenase (COX-2), tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), and inducible nitric oxide synthase (iNOS) and the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, p38 MAPK, c-Jun N-terminal kinase (JNK), heme oxygenase (HO-1), p65, and IκBα were all identified by western blotting assay. The level of nitric oxide (NO) was measured by spectrometer analysis. The nuclear translocation of p65 nuclear factor kappa B (NF-κB) was assessed by the confocal microscopic staining method. Native polyacrylamide gel electrophoresis was performed to perceive the activity of antioxidant enzyme catalase (CAT). Results AU expressively reduced NO production and COX-2, TNF-α, IL-1 β, and iNOS expression in LTA-stimulated cells. AU at higher concentration (10 µM) inhibited ERK and JNK, but not p38 phosphorylation induced by LTA. Moreover, AU blocked IκB and p65 phosphorylation, and p65 nuclear translocation. However, AU pretreatment was not effective on antioxidant HO-1 expression, CAT activity, and reduced glutathione (GSH, a nonenzymatic antioxidant), in LTA-induced RAW 264.7 cells. Conclusion The findings of this study advocate that AU shows anti-inflammatory effects via reducing NF-κB/MAPKs signaling pathways.

Highlights

Various chemicals and pathogens considered as harmful stimuli produce inflammation, which is a protective response of our body
lipoteichoic acid- (LTA-)Induced nitric oxide (NO) Production and inducible nitric oxide synthase (iNOS) Were Inhibited by AU
We found that auraptene (5 and 10 μM) did not display cytotoxicity in both control and lipoteichoic acid (LTA)-stimulated RAW cells

Summary

Introduction

Various chemicals and pathogens considered as harmful stimuli produce inflammation, which is a protective response of our body. Inflammation can be classified as acute and chronic, which induces pain and tissue injuries. In chronic inflammation, persistence of the inflammatory reactions could induce the migration of lymphocytes and macrophages to the damaged tissues [3]. Chronic inflammatory responses have been associated with the progression of various diseases such as asthma, arthritis, and neurodegenerative disorders [4]. Studies have established the involvement of several mediators including prostaglandin E2 (PGE2) in inflammatory events. Various symptoms including bone metabolism, wound healing, kidney function, blood vessel, and the immune responses have been associated with PGE2 secretion [5]. Cyclooxygenase (COX-2) protein can be expressed in response to physical, chemical, and biological stimulation [6]. E production of PGE2 can be augmented by COX-2, which denotes a central step in the events of inflammation Cyclooxygenase (COX-2) protein can be expressed in response to physical, chemical, and biological stimulation [6]. e production of PGE2 can be augmented by COX-2, which denotes a central step in the events of inflammation

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Conclusion