title: Suppressive effects of a pyrazole derivative of curcumin on airway inflammation and remodeling.
abstract: To advance the control of airway epithelial cell function and asthma, we investigated the effects of a new curcumin derivative, CNB001, which possesses improved pharmacological properties. Normal human bronchial epithelial (NHBE) cells were stimulated with synthetic double-stranded RNA, Poly(I:C). CNB001 significantly suppressed IL-6, TNF-α, and GM-CSF production by NHBE cells, and did so more effectively than did curcumin or dexamethasone (DEX). CNB001 significantly inhibited the decrease of E-cadherin mRNA expression and increase of vimentin mRNA expression observed in NHBE cells induced by a combination of TGF-β1 and TNF-α, which are markers of airway remodeling. In NHBE cells stimulated by TGF-β1, CNB001 significantly downregulated the level of active serine peptidase inhibitor clade E member (SERPINE) 1, which is also reported to be related to airway remodeling. Whereas DEX alone significantly increased the active SERPINE1 level, the combination of DEX and CNB001 significantly suppressed active SERPINE1. In addition, CNB001 significantly suppressed neutrophil infiltration, IL-6, TNF-α, IL-13 and active SERPINE1 production in bronchoalveolar lavage fluid of the murine asthma model, which was not observed in the case of DEX. In conclusion, the curcumin derivative, CNB001, is a promising candidate to treat asthma associated with neutrophilic airway inflammation and remodeling.
authors.affiliation: Department of Pharmacotherapy, Research Institute of Pharmaceutical Sciences Musashino University, Tokyo, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Narumoto
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Matsuo
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sakaguchi
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Shoji
authors.forename: Naohide
authors.initials: N
authors.lastname: Yamashita
authors.forename: David
authors.initials: D
authors.lastname: Schubert
authors.forename: Kazuho
authors.initials: K
authors.lastname: Abe
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Horiguchi
authors.forename: Takahide
authors.initials: T
authors.lastname: Nagase
authors.forename: Naomi
authors.initials: N
authors.lastname: Yamashita
mesh_terms: D056151:Airway Remodeling / Q000187:drug effects*; D000818:Animals; D001249:Asthma / Q000188:drug therapy*; D001980:Bronchi / Q000187:drug effects*; D015820:Cadherins / Q000096:biosynthesis; D003474:Curcumin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012330:RNA, Double-Stranded / Q000633:toxicity
chemical_list: C529348:CNB 001; D015820:Cadherins; D016207:Cytokines; D005938:Glucocorticoids; D017395:Plasminogen Activator Inhibitor 1; D011720:Pyrazoles; D012330:RNA, Double-Stranded; C051321:SERPINE1 protein, human; D003907:Dexamethasone; D003474:Curcumin