1.Inhibitory effects of 1,8-cineol on ovalbumin-induced lung inflammation and airway hyperresponsiveness in asthmatic guinea pigs
Qiaoping XU ; Yan WANG ; Fadi TANG ; Jinfang XIA ; Junbo LIU ; Xiaojing ZHAO ; Rulian BIAN
Chinese Journal of Pharmacology and Toxicology 2010;24(1):35-43
OBJECTIVE To investigate the effects of 1,8-cineol on lung functions and mechanism in asthmatic guinea pigs. METHODS The guinea pig model was performed by intraperitoneal injection of the 0.5 ml Al(OH)_3 gel containing OVA 20 μg. The guinea pigs were constructed by immunization of intraperitoneal injection on the 0 day and the 7th day, and the experiment was performed on the 28th day. The effect of 1,8-cineol 10, 30 and 100 ml·kg~(-1) on the airway resistance(R_(aw)) and dynamic lung compliance (C_(dyn)) of asthmatic guinea pigs 1 h after challenge of OVA. The changes in leukocyte and different kinds of leukocyte in bronchoalveolar lavage fluid (BALF) after the challenge of OVA have been studied. The levels of eosinophil cationic protein (ECP), interleukin(IL)-4, IL-8 and tumor necrosis factor (TNF)-α in lungs of guinea pigs were determined using enzyme-linked immunosorbent assay (ELISA). The changes in R_(aw) and C_(dyn) of asthmatic guinea pigs were investigated 17 h after challenge of OVA and inhalated methacholine (MCh). The changes in leukocyte and different kinds of leukocyte in BALF after the challenge of OVA have been studied. The levels of ECP, IL-4, IL-8 and TNF-α in lungs of guinea pigs were determined using ELISA. RESULTS 1,8-Cineol inhibited increase in R_(aw) and decrease in C_(dyn) from 1 to 30 min after challenge of OVA in model group. The levels of ECP, IL-4 and TNF-α in asthmatic model group were higher than those in normal control group(P<0.05). The levels of ECP, IL-4 and TNF-α of 1,8-cineol 100 mg·kg~(-1) group were significantly lower than those in asthmatic model group (P<0.01). The level of IL-8 of asthmatic model group didn't have any significant difference from that of control group. 1,8-Cineol 100 mg·kg~(-1) could significantly decrease the numbers of leukocyte and the percent of eosinophils in BALF. Seventeen hours after challenge of OVA, R_(aw) and C_(dyn) of asthmatic model group were higher than these of control group (P<0.05, P<0.01); 1,8-cineol 100 mg·kg~(-1) significantly inhibited the increase in R_(aw), compared with model group (P<0.05); 1,8-cineol 10, 30 and 100 mg·kg~(-1) improved the decrease in C_(dyn) after MCh-induced in model group which were challenged by OVA after 17 h; 1,8-cineol 100 mg·kg~(-1) could significantly decrease the numbers of leukocyte and the percent of neutrophils, the levels of ECP, IL-8 and TNF-α compared with asthmatic group. The level of IL-4 in asthmatic model group didn't have any significant difference from that in normal control group. CONCLUSION In the course of early stage of asthma, 1,8-cineol inhibites the asthma by decreasing the number of eosinophils and down-regulating the activity of EPO. In the course of later stage of asthma, 1,8-cineol inhibits or improves the aggravation and lasting states of asthma which is directly coursed by neutrophils accumulating in the BALF that related to the increase in IL-8.