Protocatechuic acid suppresses ovalbumin-induced airway inflammation in a mouse allergic asthma model

• Published in: International immunopharmacology 2013-04, Vol.15 (4), p.780-788
• Main Authors: Wei, Miaomiao, Chu, Xiao, Guan, Mingfeng, Yang, Xiaofeng, xie, Xianxing, Liu, Fang, Chen, Chengzhen, Deng, Xuming
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Airway inflammation; Animals; Anti-Asthmatic Agents - administration & dosage; Anti-Asthmatic Agents - isolation & purification; Anti-Asthmatic Agents - therapeutic use; Asthma; Asthma - chemically induced; Asthma - drug therapy; Asthma - immunology; Blotting, Western; Bronchoalveolar Lavage Fluid - chemistry; Bronchoalveolar Lavage Fluid - cytology; Bronchoalveolar Lavage Fluid - immunology; Cytokines - blood; Cytokines - immunology; Dose-Response Relationship, Drug; Drugs, Chinese Herbal - administration & dosage; Drugs, Chinese Herbal - isolation & purification; Drugs, Chinese Herbal - therapeutic use; Female; Hydroxybenzoates - administration & dosage; Hydroxybenzoates - isolation & purification; Hydroxybenzoates - therapeutic use; Immunoglobulin E - blood; Immunoglobulin E - immunology; Lung - drug effects; Lung - immunology; Lung - pathology; MAPK; Methacholine Chloride - pharmacology; Mice; Mice, Inbred BALB C; NF-κB; Ovalbumin - immunology; Protocatechuic acid; Respiratory Hypersensitivity - chemically induced; Respiratory Hypersensitivity - drug therapy; Respiratory Hypersensitivity - immunology
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2013.01.010

Protocatechuic acid (PCA) has been isolated from the leaves of ilex chinenses and has numerous pharmacologic effects, including anti-inflammatory and antitumoral activities. This study aims to evaluate the antiasthma activity of PCA and investigate its possible molecular mechanisms. BALB/c mice were sensitized and challenged to ovalbumin (OVA).Then mice were intraperitoneally (i.p.) injected with PCA 1h before OVA challenge. We found that PCA treatment at 15 or 30mg/kg significantly decreased OVA-induced airway hyper-responsiveness (AHR) to inhaled methacholine. Type 2 helper T cell (Th2) cytokines in bronchoalveolar lavage (BAL) fluid, such as interleukin-4 (IL-4), interleukin 5 (IL-5) and interleukin-13 (IL-13), and serum OVA-specific immunoglobulin E (IgE) levels, were also reduced by PCA. Moreover treatment with PCA markedly decreased the number of inflammatory cells in BALF and attenuated OVA-induced mRNA expression of CCl11, CCR3, Muc5ac, acidic mammalian chitinase (AMCase), chitinase 3-like protein 4 (Ym2) and E-selectin in lung tissues, lung histopathological studies showed that PCA inhibited inflammatory cell infiltration and mucus hypersecretion compared with the OVA-induced mice group. We then investigated the possible molecular mechanisms which might be implicated in PCA activity. Our results suggested that the protective effect of PCA might be mediated by the inhibition of the extracellular signal-regulated protein kinase (ERK), p38 Mitogen-activated protein kinase (MAPK) phosphorylation and the nuclear factor-κB (NF-κB) activation. ► PCA reduced Th2 cytokines and eosinophilia aggregation into the lungs. ► PCA inhibited mRNA expression of CCl11, CCR3, AMCase, E-selectin, Ym2 and Muc5ac in lung tissues. ► PCA inhibited mucus hyper-secretion by goblet cells in the airway. ► PCA inhibited the NF-κB and MAPK signaling pathways. ► PCA reduced OVA-specific IgE serum levels and histological changes.