The Protective Effects And Mechanism Of PCA On Mouse Allergic Asthma Model

Allergic asthma is a chronic airway disorder characterized by airway inflammation, mucushypersecretion, and AHR. Cumulative evidence showed that these inflammatory responses arecontributed by Th2cells, together with other inflammatory cells such as eosinophils, macrophagesand neutrophils, as well as inflammatory cytokines and chemokines. In the past few decades, theincidence, morbidity and mortality of the allergic asthma around the world are growing at analarming rate. Although the pathophysiology of asthma has been extensively investigated, there isstill no cure for this disease. Allergens play an important role in the initiation and development ofasthma. OVA is one of the most common allergen used in lab. Aluminum hydroxide gel is theimmune adjuvant of OVA. Our experiment establishes the mouse allergic asthma model by OVAsensitization. Protocatechuic acid (PCA) is a major benzoic acid derivative found in vegetables, nuts,brown rice, fruits, and herbal medicines. Numerous pharmacologic effects, such as antioxidative,antibacterial, anti-inflammatory and antitumor promotion activities, have been attributed to PCA.We use OVA-induced mouse allergic asthma to study the anti-inflammatory activities and relatedmechanisms of PCA. This will provide theoretical basis for the clinical application.BALB/c mice (female,18-20g each) were randomly divided into six groups. Mice weresensitized with OVA adsorbed in100μg/mL of Imject Alum by i.p. injection on day0and day14.On days25-27, the mice were anesthetized again and instilled intranasally (i.n.) with OVA (100μg) in PBS (50μl). PCA (5,15and30mg/kg) and DEX (2mg/kg) were given an i.p. injection ondays25-27,1h prior to OVA administration. DEX (2mg/kg) was injected as a positive control.Control mice received the same immunization, but were exposed to phosphate-buffered saline(PBS) instead of OVA during airway challenge. Mice were anesthetized24h after the lastOVA challenge. BALF, blood and lung tissues were collected for relevant measurement.Results showed that PCA effectively reduce the OVA-induced Th2cytokines and inflammatory cells. PCA treatment significantly inhibited the OVA-induced inflammatory infiltration, goblet cellhyperplasia and mucus overproduction in a mice model of asthma. And PCA significantlydecreased the OVA-specific serum IgE levels. Then we observed the AHR of mouse by intravenousadministration of different methacholine. We found that PCA significantly reducedOVA-induced AHR by improving the lung compliance and reducing pulmonary resistance.Then we further studied the influence of PCA on chemokine, chemokine receptor, and someairway inflammation factors associated with asthma. Our results showed that treatment withPCA demonstrated the suppression of CCL11， CCR3， Muc5ac, AMCase, Ym2, andE-selectin. At last, we investigated the effect of PCA on MAPK and NF-κB activation in a mousemodel of asthma. Our research of mechanism confirmed that PCA significantly inhibited theactivation of MAPK (ERK, p38) and NF-κB.Based on the research above, we found that PCA can effectively improve OVA-induced allergicasthma in a dose-dependent manner. And the suppression of NF-κB and MAPK activation maybe principal therapeutic mechanism of PCA. Although our study has shed some light on thisissue, further and more comprehensive studies are still required before the full clinical application.