title: Identification and Characterization of Baicalin as a Phosphodiesterase 4 Inhibitor.
abstract: Asthma is a chronic inflammatory disease of lung airways, and pharmacological inhibitors of cyclic adenosine monophosphate-specific phosphodiesterase 4 (PDE4) have been considered as therapeutics for the treatment of asthma. However, development of PDE4 inhibitors in clinical trials has been hampered because of the severe side effects of non-selective PDE4 inhibitors. Here, screening of a plant extract library in conjunction with dereplication technology led to identification of baicalin as a new type of PDE4-selective inhibitor. We demonstrated that while rolipram inhibited the enzyme activity of a range of PDE4 subtypes in in vitro enzyme assays, baicalin selectively inhibited the enzyme activity of PDE4A and 4B. In addition, baicalin suppressed lipopolysaccharide-induced TNF-α expression in macrophage where PDE4B plays a key role in lipopolysaccharide-induced signaling. Furthermore, baicalin treatment in an animal model of allergic asthma reduced inflammatory cell infiltration and TNF-α levels in bronchoalveolar lavage fluids, indicating that the antiinflammatory effects of baicalin in vivo are attributable, in part, to its ability to inhibit PDE4.
authors.affiliation: Bio-Center, Gyeonggi Institute of Science and Technology Promotion, Suwon, Gyeonggi-do, 443-270, Korea.
authors.forename: Kyuhee
authors.initials: K
authors.lastname: Park
authors.affiliation: Bio-Center, Gyeonggi Institute of Science and Technology Promotion, Suwon, Gyeonggi-do, 443-270, Korea.
authors.forename: Jong Suk
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Bio-Center, Gyeonggi Institute of Science and Technology Promotion, Suwon, Gyeonggi-do, 443-270, Korea.
authors.forename: Jung Suk
authors.initials: JS
authors.lastname: Choi
authors.affiliation: Bio-Center, Gyeonggi Institute of Science and Technology Promotion, Suwon, Gyeonggi-do, 443-270, Korea.
authors.forename: Yeon-Ju
authors.initials: YJ
authors.lastname: Nam
authors.affiliation: Bio Convergence Center, Jeju Technopark, Jeju city, Jeju-do, 699-121, Korea.
authors.forename: Jong-Heon
authors.initials: JH
authors.lastname: Han
authors.affiliation: Bio Convergence Center, Jeju Technopark, Jeju city, Jeju-do, 699-121, Korea.
authors.forename: Hoo-Dhon
authors.initials: HD
authors.lastname: Byun
authors.affiliation: Bio-Center, Gyeonggi Institute of Science and Technology Promotion, Suwon, Gyeonggi-do, 443-270, Korea.
authors.forename: Myung-Jin
authors.initials: MJ
authors.lastname: Song
authors.affiliation: Bio-Center, Gyeonggi Institute of Science and Technology Promotion, Suwon, Gyeonggi-do, 443-270, Korea.
authors.forename: Joa-Sup
authors.initials: JS
authors.lastname: Oh
authors.affiliation: Bio Convergence Center, Jeju Technopark, Jeju city, Jeju-do, 699-121, Korea.
authors.forename: Sung Gyu
authors.initials: SG
authors.lastname: Kim
authors.affiliation: Bio-Center, Gyeonggi Institute of Science and Technology Promotion, Suwon, Gyeonggi-do, 443-270, Korea.
authors.forename: Yongmun
authors.initials: Y
authors.lastname: Choi
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D004195:Disease Models, Animal; D005419:Flavonoids / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D041681:NIH 3T3 Cells; D058988:Phosphodiesterase 4 Inhibitors / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology*; D000067996:RAW 264.7 Cells; D020889:Rolipram / Q000494:pharmacology; D027824:Rosaceae / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D005419:Flavonoids; D008070:Lipopolysaccharides; D058988:Phosphodiesterase 4 Inhibitors; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; C038044:baicalin; D020889:Rolipram
keywords: TNF-α; asthma; baicalin; phosphodiesterase