Pretreatment of ferulic acid attenuates inflammation and oxidative stress in a rat model of lipopolysaccharide-induced acute respiratory distress syndrome

Abstract

Acute respiratory distress syndrome (ARDS) is a fatal clinical condition that can be caused by pulmonary and non-pulmonary diseases. Oxidative stress and inflammation play key roles in the development of ARDS. In this study, we investigated whether ferulic acid (FA), an anti-oxidant, was beneficial for prophylaxis of ARDS. We established an ARDS rat model using lipopolysaccharide (LPS) administration. Lung injury was assessed by lung wet/dry ratio and broncho-alveolar lavage fluid (BALF) analysis. Hematoxylin and eosin staining was performed to evaluate the histological changes of the lungs. Enzyme-linked immunosorbent assay (ELISA) and immunoblotting were performed to detect proteins in BALF and lung tissue, respectively. Pulmonary function was determined by testing the oxygen level in BALF. FA pretreatment significantly alleviated LPS-induced pulmonary histological changes. FA reversed LPS-induced changes of lung wet/dry ratio, total protein in BALF, P(A-a)O2, and PaO2/FiO2. In addition, LPS dramatically up-regulated the secretion of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and IL-10 in BALF (P < 0.01). However, pretreatment of FA significantly improved LPS-induced inflammation. We found that FA indeed reduced oxidative stress in the lungs by testing malondialdehyde level, myeloperoxidase level, and total anti-oxidant capacity. We also proved that FA inactivated multiple mitogen-activated protein kinase signaling pathways in the lungs. In conclusion, FA alleviated LPS-induced ARDS through its anti-inflammatory and anti-oxidant activities.

Ferulic Acid Ameliorates Lipopolysaccharide-Induced Barrier Dysfunction via MicroRNA-200c-3p-Mediated Activation of PI3K/AKT Pathway in Caco-2 Cells

“…In LPS-stimulated RAW 264.7 cells, 100 mM FA reduces the translocation of NF-E2-related factor 2 (Nrf2) and nuclear transcription factor-kB (NF-kB) into the nuclei through a reduction of the expression of phosphorylated IKK and consequently inhibits proinflammatory IL-6 production (Lampiasi and Montana, 2016;Lampiasi and Montana, 2018). FA down-regulates mitogen-activated protein kinase signaling (p38, ERK and JNK) and reserved the antioxidant activity in the injured lungs induced by LPS stimulation (Zhang et al, 2018). Several studies also demonstrated that FA may target Toll-like receptor 4 (TLR4) to inhibit LPS infection.…”

Ferulic acid ameliorates pentylenetetrazol-induced seizures by reducing neuron cell death

“…Drug treatments were administered once daily for 28 days. The dose of FA (60 mg/kg) was based on the following studies (Mancuso et al, 2014;Hassanzadeh et al, 2017;Zhang et al, 2018)with a modification. There was no effect of pre-treatment with ferulic acid (50 mg/kg), but there were significant effects at doses of 75 mg/kg and 100 mg/kg, and there were no differences between these two doses (Mancuso et al, 2014;Hassanzadeh et al, 2017).…”

“…Fifty mg/kg FA caused the attenuation of inflammation in lipopolysaccharide-induced rat acute respiratory distress syndrome (Zhang et al, 2018). The time of FA pre-treatment and the treatment duration were based on a previous study (Hassanzadeh et al, 2017), but our treatment period was 10 days longer than their 18-day treatment, as they failed to show an improvement of locomotive activities.…”

The Effects and Mechanisms of Cyanidin-3-Glucoside and Its Phenolic Metabolites in Maintaining Intestinal Integrity

“…Recent studies have suggested that C3G potentially exerts functions primarily through C3G metabolites (C3G-Ms) [7], and more than 20 kinds of C3G-Ms have been identified in serum by a pharmacokinetics study in humans [8]. Although the function and mechanism of C3G-Ms are still not clear, protocatechuic acid (PCA) [9][10][11][12], phloroglucinaldehyde (PGA) [1], vanillic acid (VA) [13][14][15], ferulic acid (FA) [16][17][18][19], and their derivates represent the main bioactive metabolites of C3G due to their antioxidant and anti-inflammatory properties. Figure 1.…”