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.
(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.
Yang
Eun Ju
EJ
Department of Biomedical Laboratory Science, School of Medicine, Eulji University, Daejeon, Republic of Korea.
Song
Gyu-Yong
GY
Lee
Ji-Sook
JS
Yun
Chi-Young
CY
Kim
In Sik
IS
D000179:Acrylates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D001578:Benzopyrans / Q000737:chemistry; D002087:Butyrates / Q000737:chemistry; D002839:Chromans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis; D007073:Immunoglobulin E / Q000096:biosynthesis; D007962:Leukocytes / Q000276:immunology; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009093:Mucus / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology*; D011014:Pneumonia / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D013237:Stereoisomerism; D018418:Th2 Cells / Q000378:metabolism
C540133:3-(3,4-dihydroxy-phenyl)-acrylic acid 2,2-dimethyl-8-oxo-3,4-dihydro-2H,8H-pyrano(3,2-g)chromen-3-yl-ester; D000179:Acrylates; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001578:Benzopyrans; D002087:Butyrates; D002839:Chromans; D016207:Cytokines; D007073:Immunoglobulin E; D010047:Ovalbumin; C101278:decursin