Effects of Hydroxy Pentacyclic Triterpene Acids from Forsythia viridissima on Asthmatic Responses to Ovalbumin Challenge in Conscious Guinea Pigs

For the identification of anti-inflammatory ingredients from Forsythiae fructus (FF), we isolated three hydroxyl pentacyclic triterpene acids (HTAs), namely, oleanolic acid, ursolic acid, and betulinic acid, from an ethylacetate fraction of FF, and evaluated the effect of these triterpene acids on asthmatic guinea pigs by measuring specific airway resistance (sRaw) during both immediate-phase response (IAR) and late-phase response (LAR) following ovalbumin challenge using a double-chambered plethysmograph. Evaluation of leukocytes and chemical mediators in bronchoalveolar lavage fluid (BALF), in addition to a histopathological survey, was also performed. Ursolic, oleanolic and betulinic acids dosed at 12.5 mg/kg significantly (p < 0.05) decreased sRaw by 46.80%, 46.54% and 44.27% during in IAR, respectively. And ursolic acid (25 mg/kg), and oleanolic and betulinic acids (50 mg/kg) significantly (p < 0.05) decreased sRaw by 38.19%, 38.15% and 35.55% in LAR, respectively. Histamine and phospholipase A(2) activity in BALF were significantly decreased by HTAs at 12.5 mg/kg, whereas eosinophil peroxide (EPO) activity in BALF and recruitment of eosinophils were significantly decreased by HTAs at 25 mg/kg, as well as improvement of pathological changes. However, betulinic acid at 12.5 mg/kg, and ursolic and oleanolic acids at 25 mg/kg significantly inhibited leukocytes in BALF, especially eosinophils and neutrophils. Three HTAs were found to have dose-dependent anti-asthmatic effects and ursolic acid is the most active, but their activities were less than those of sodium cromoglycate, salbutamol, and dexamethasone. These results indicate HTAs had anti-asthmatic activity by decreasing of sRaw, and eosinophil recruitment and release of inflammatory mediators into the lungs.