title: Natural phosphodiesterase-4 (PDE4) inhibitors from Crotalaria ferruginea.
abstract: Bioassay-guided fractionation of the ethanol extract of the Chinese folk medicine Crotalaria ferruginea led to the isolation of a new isoflavonoid, 4'-hydroxy-2'-methylalpinum-isoflavone (1), and eight known analogs (2-9). Their structures were elucidated by spectroscopic analysis. Compounds 1, 2, 5, and 8 showed inhibitory activities against phosphodiesterase-4 (PDE4), a therapeutic target of asthma, with IC50 values ranging from 2.57 to 8.94 μM. The possible action mechanism and the structure-activity relationship (SAR) of the active isoflavonoids were explored by using molecular docking and molecular dynamics (MD) simulation methods. Our study herein may explain the anti-inflammatory function of this plant in Chinese folk medicine.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, China.
authors.forename: Ye-Na
authors.initials: YN
authors.lastname: Liu
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, China.
authors.forename: Yi-You
authors.initials: YY
authors.lastname: Huang
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, China.
authors.forename: Jing-Mei
authors.initials: JM
authors.lastname: Bao
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, China.
authors.forename: Ying-Hong
authors.initials: YH
authors.lastname: Cai
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, China.
authors.forename: Yan-Qiong
authors.initials: YQ
authors.lastname: Guo
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, China.
authors.forename: Shao-Nan
authors.initials: SN
authors.lastname: Liu
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, China. Electronic address: luohb77@mail.sysu.edu.cn.
authors.forename: Hai-Bin
authors.initials: HB
authors.lastname: Luo
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, China. Electronic address: yinsh2@mail.sysu.edu.cn.
authors.forename: Sheng
authors.initials: S
authors.lastname: Yin
mesh_terms: D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D029864:Crotalaria / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D007529:Isoflavones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008516:Medicine, Chinese Traditional; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D058988:Phosphodiesterase 4 Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D013329:Structure-Activity Relationship
chemical_list: C000594233:4'-hydroxy-2'-methylalpinum-isoflavone; D000893:Anti-Inflammatory Agents; D007529:Isoflavones; D058988:Phosphodiesterase 4 Inhibitors; D010936:Plant Extracts
keywords: Crotalaria ferruginea; Isoflavonoids; Molecular dynamics simulation; PDE4; SAR