Inhibitory effects of diterpene acids from root of Aralia cordata on IgE-mediated asthma in guinea pigs.
This study evaluated the anti-asthmatic activities of four diterpene acids isolated from Aralia cordata root that are proposed to be the active ingredients in its traditional use as a treatment for inflammation, overheating, pain and spasm in Korea. The diterpene acids were identified as kaurenoic acid, 7-oxo-sandaracopimaric acid, 17-hydroxy-ent-kaur-15-en-19-oic acid, and hederagenin, by comparing their phytochemical and spectroscopic data with previous reports. The effects of diterpene acids on asthma were evaluated by determining the specific airway resistance (sRaw) during the immediate asthmatic response (IAR) and the late-phase asthmatic response (LAR) in guinea pigs with IgE-mediated asthma. Recruitment of leukocytes and the presence of chemical mediators in bronchoalveolar lavage fluid (BALF) were determined, and histopathological surveys performed. The four diterpene acids dosed at 25 approximately 100 mg/kg had dose-dependently anti-asthmatic effects: 7-oxo-sandaracopimaric acid > 17-hydroxy-ent-kaur-15-en-19-oic acid > kaurenoic acid > hederagenin. 7-oxo-sandaracopimaric acid (25 mg/kg) significantly (p < 0.05) inhibited sRaw by 59.5% in IAR and LAR, and also dose-dependently inhibited recruitment of eosinophils and neutrophils into lung and release of chemical mediators, histamine, and the activity of phospholipase A(2) and eosinophil peroxidase in BALF. 7-Oxo-sandaracopimaric acid had the highest activity among the diterpene acids. But its effect was lower than cromolyn sodium, salbutamol, or dexamethasone in both the IAR and the LAR. These results suggested that C(7)-oxo radical of 7-oxo-sandaracopimaric acid was more active than the C(7)-hydroxy and hydrogen of the other compounds, and showed diterpene acids have anti-asthmatic effects, supporting the traditional application of this herb in treating IgE-mediated asthma.
Cho
Joong Hyung
JH
Division of Pathophysiology, College of Pharmacy, Chung-Ang University, Seoul 156-756, Republic of Korea.
Lee
Ji Yun
JY
Sim
Sang Soo
SS
Whang
Wan Kyun
WK
Kim
Chang Jong
CJ
D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D027983:Aralia; D001249:Asthma / Q000188:drug therapy*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000378:metabolism; D006168:Guinea Pigs; D006632:Histamine / Q000378:metabolism; D007073:Immunoglobulin E / Q000378:metabolism*; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000378:metabolism; D009828:Oleanolic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D054467:Phospholipases A2 / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology
D004224:Diterpenes; D010936:Plant Extracts; C008037:17-hydroxy-ent-kaur-15-en-19-oic acid; D007073:Immunoglobulin E; C051436:kaurenoic acid; D009828:Oleanolic Acid; D006632:Histamine; D054467:Phospholipases A2; C025763:hederagenin