Methyl P-Coumarate Ameliorates the Inflammatory Response in Activated-Airway Epithelial Cells and Mice with Allergic Asthma

Abstract

Methyl p-coumarate (methyl p-hydroxycinnamate) (MH) is a natural compound found in a variety of plants. In the present study, we evaluated the ameliorative effects of MH on airway inflammation in an experimental model of allergic asthma (AA). In this in vitro study, MH was found to exert anti-inflammatory activity on PMA-stimulated A549 airway epithelial cells by suppressing the secretion of IL-6, IL-8, MCP-1, and ICAM-1. In addition, MH exerted an inhibitory effect not only on NF-κB (p-NF-κB and p-IκB) and AP-1 (p-c-Fos and p-c-Jun) activation but also on A549 cell and EOL-1 cell (eosinophil cell lines) adhesion. In LPS-stimulated RAW264.7 macrophages, MH had an inhibitory effect on TNF-α, IL-1β, IL-6, and MCP-1. The results from in vivo study revealed that the increases in eosinophils/Th2 cytokines/MCP-1 in the bronchoalveolar lavage fluid (BALF) and IgE in the serum of OVA-induced mice with AA were effectively inhibited by MH administration. MH also exerted a reductive effect on the immune cell influx, mucus secretion, and iNOS/COX-2 expression in the lungs of mice with AA. The effects of MH were accompanied by the inactivation of NF-κB. Collectively, the findings of the present study indicated that MH attenuates airway inflammation in mice with AA, suggesting its potential as an adjuvant in asthma therapy.

Aromadendrin inhibits PMA-induced cytokine formation/NF-κB activation in A549 cells and ovalbumin-induced bronchial inflammation in mice

“…Recent studies have revealed that the combination of airway epithelial cells and eosinophils is weakened by the suppression of airway epithelial cell-derived cytokines such as IL-6 and MCP-1 [ 15 ]. Compounds that can suppress airway epithelial cell-derived cytokines and airway cell-eosinophil adhesion exert ameliorative effects against bronchial inflammation in experimental models of AA [ 16 , 35 , 36 ]. In our in vitro study, ARO inhibited not only IL-1β, IL-6, TNF-α, and MCP-1 production in A549 cells but also airway cell-eosinophil cohesion.…”

“…To detect immune cells and Th2 cytokines in the BALF, mice were anesthetized as per previously reported conditions (intraperitoneal injection of Zoletil and xylazine) [ 16 ]. Immune cell morphology was distinguished using Diff-Quik staining, and the number of cells was determined using a light microscope (400× magnification) [ 31 ].…”

“…Phorbol 12-myristate 13-acetate (PMA) induces cytokine production and NF-κB activation in A549 airway epithelial cells [ 15 ]. The utility of ovalbumin (OVA) for AA induction in vivo has been confirmed through its ability to induce eosinophil/macrophage inrush, IL-4/IL-5/IL-13/IgE/mucus generation, iNOS/COX-2 upregulation, and phosphorylation of NF-κB [ 16 , 17 ].…”

Effects of increasing sensitizing doses of ovalbumin on airway hyperresponsiveness in asthmatic mice

“…[7][8][9][10] The previous study has demonstrated that intraperitoneal injection of OVA and alum once a week for 2 weeks is the most straightforward and effective approach to induce an asthmatic reaction in mice. 11 However, the inconsistent use of sensitizing OVA doses in current studies [12][13][14] and the lack of research on their effect on AHR necessitate further investigation. Therefore, we conducted a study using increasing doses (0, 10, 20, 50, and 100 μg) of sensitizing OVA in a BALB/c murine model of asthma to evaluate their impact on AHR to methacholine (MCh), as well as histological changes, eosinophilic infiltration, and epithelial damage.…”

Health Properties of Plant Bioactive Compounds: Immune, Antioxidant, and Metabolic Effects

“…Methyl p-coumarate, an esterified derivative of p-coumaric acid and a naturally occurring compound in plants, has been shown to be an effective agent for reducing inflammation in an experimental in vivo model of allergic asthma, reducing the influx of immune cells and mucus secretion in the lung, among other activities [9].…”