title: Baicalin is anti-inflammatory in cigarette smoke-induced inflammatory models in vivo and in vitro: A possible role for HDAC2 activity.
abstract: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease characterized by airway obstruction and progressive lung inflammation, which is insensitive to corticosteroids therapies. In this study, we investigated the mechanism underlying the attenuation of cigarette smoke (CS)-induced respiratory inflammation by baicalin, a flavonoid compound isolated from the root of Scutellaria baicalensis Georgi, in vivo and in vitro. In vivo, mice were exposed to smoke of 15 cigarettes for 1 h/day, 6 days/week for 3 months and dosed with baicalin (25, 50 and 100mg/kg) or dexamethasone (1mg/kg). In vitro, A549 cells were incubated with baicalin (10, 50 and 100 μM) or dexamethasone (10(-12), 10(-10), 10(-8) and 10(-6)M) followed by treatments with cigarette smoke extract (CSE, 2.5 and 5%), or TNF-α (10 ng/ml), or trichostatin A (TSA, 100 ng/ml). We found that baicalin significantly protected pulmonary function and attenuated CS-induced inflammatory response by decreasing inflammatory cells and production of TNF-α, IL-8 and MMP-9. This result was not found in the group treated with dexamethasone. Baicalin also showed efficacy in enhancing histone deacetylase (HDAC)2 activity and protein expression, however, it did not affect HDAC2 mRNA. Further studies revealed that baicalin inhibited HDAC2 phosphorylation, suggesting that it may directly affect the protein structure and effect by modification at post-translational level. Together these results suggest that baicalin has anti-inflammatory effects in cigarette smoke induced inflammatory models in mice and A549 cells, possibly achieved by modulating HDAC2.
authors.affiliation: Department of Integrative Medicine, Huashan Hospital, Fudan University, 12 Middle Urumqi Road, Shanghai, China.
authors.forename: Lulu
authors.initials: L
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Bao
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Wu
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Duan
authors.forename: Baojun
authors.initials: B
authors.lastname: Liu
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.forename: Weiyi
authors.initials: W
authors.lastname: Gong
authors.forename: Yubao
authors.initials: Y
authors.lastname: Lv
authors.forename: Hongying
authors.initials: H
authors.lastname: Zhang
authors.forename: Qingli
authors.initials: Q
authors.lastname: Luo
authors.forename: Xiao
authors.initials: X
authors.lastname: Wu
authors.forename: Jingcheng
authors.initials: J
authors.lastname: Dong
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000008:administration & dosage / Q000627:therapeutic use*; D056464:Histone Deacetylase 2 / Q000378:metabolism*; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D005419:Flavonoids; D009687:Nuclear Proteins; D014028:Tobacco Smoke Pollution; C038044:baicalin; C533424:Hdac2 protein, mouse; D056464:Histone Deacetylase 2