A Novel (S)-( )-Decursin Derivative, (S)-( )-3-(3,4-Dihydroxy-phenyl)-acrylic Acid 2,2-Dimethyl-8-oxo-3,4-dihydro-2H,8H-pyrano[3,2-g]chromen-3-yl-ester, Inhibits Ovalbumin-Induced Lung Inflammation in a Mouse Model of Asthma

作者：Yang Eun Ju; Song Gyu Yong; Lee Ji Sook; Yun Chi Young; Kim In Sik^*

来源：Biological & Pharmaceutical Bulletin, 2009, 32(3): 444-449.

DOI：10.1248/bpb.32.444

• (S)-( )-decursin derivative
• asthma
• eosinophil
• immunoglobulin E

(S)-( )-Decursin is a coumarin compound present in herbal extracts that has various biological activities. (S)-( )-Decursin attenuates pathophysiologic progression in cancer, bacterial infection and neuropathy. Asthma is an inflammatory disease associated with increased infiltration of leukocytes, especially eosinophils, and secretion of mucus into the airways. Although (S)-( )-decursin, as well as (S)-( )-decursin analogues, have various pharmacological properties, the effect of these compounds on asthma is not known. In the present study, we synthesized (S)-( )-3-(3,4-dihydroxy-phenyl)-acrylic acid 2,2-dimethyl-8-oxo-3,4-dihydro-2H,8H-pyrano[3,2-g]chromen-3-yl-ester (compound 6, C6) from (S)-( )-decursin and examined if C6 had any inhibitory effects on lung inflammation in a mouse model of ovalbumin-induced asthma. C6 significantly inhibited the leukocytosis (p<0.01) and eosinophilia (p<0.05) in bronchoalveolar lavage (BAL) fluid. Examination of lung tissues stained with hematoxylin and eosin and periodic acid Schiff reagents showed that C6 suppressed the increased infiltration of inflammatory cells and elevated mucus hypersecretion. Protein levels of interleukin (IL)-5 (p<0.05) and eotaxin (p<0.01) were significantly reduced in BAL fluid by C6. C6 also significantly reduced total and ovalbumin-specific immunoglobulin E (IgE) levels in BAL fluid (p<0.01) as well as that in serum (p<0.05). C6 may have pharmacological effects for asthma and may be a potent therapeutic agent for the treatment of allergic airway diseases.

• 出版日期2009-3