title: Characterization and structure-activity relationship of natural flavonoids as hERG K+channel modulators.
abstract: OBJECTIVE
  Flavonoids are present in varying concentrations in plant foods and have been reported to have numerous pharmacological activities, such as anti-cancer, antioxidant, anti-inflammatory, hepatoprotective, and vasodilator effects. We found that quercetin, fisetin, and some related flavonoid derivatives could inhibit human ether-à-go-go-related gene (hERG) K+channels.
  
  
  RESULTS
  In this study, we tested the effects of a series of flavonoids on the hERG K+channel expressed in HEK293 cells. For the first time, we demonstrate that quercetin and fisetin (Fise) are potent hERG current blockers. The 50% inhibiting concentration (IC50) and maximum efficacy (Emax) of quercetin were 11.8±0.9μM and 82±2%, while those of fisetin were 38.4±6μM and 100±6%, respectively. Luteolin (Lute) was a less potent inhibitor of hERG current (48±1% at 100μM). Galangin, kaempferol, and isorhamnetin (100μM) showed weaker activity on the hERG currents.
  
  
  CONCLUSIONS
  These results suggest that quercetin, fisetin, and luteolin are potent hERG K+channel inhibitors and reveal the structure-activity relationship of natural flavonoids.
authors.affiliation: Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang, China.
authors.forename: Xiaorun
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Biochemistry, Hebei University of Chinese Medicine, Shijiazhuang, China.
authors.forename: Bingyuan
authors.initials: B
authors.lastname: Xu
authors.affiliation: Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang, China.
authors.forename: Yucong
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Department of Respiratory, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Honglin
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Respiratory, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Huiran
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Science and Technology, Hebei University of Chinese Medicine, Shijiazhuang, China.
authors.forename: Liying
authors.initials: L
authors.lastname: Kang
authors.affiliation: Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang, China.
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang, China. Electronic address: zhangjianping14@126.com.
authors.forename: Jianping
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Hebei Medical University, Shijiazhuang, China. Electronic address: jia_zf75@hotmail.com.
authors.forename: Zhanfeng
authors.initials: Z
authors.lastname: Jia
authors.affiliation: Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang, China. Electronic address: xuan_zhangt@hotmail.com.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D000072237:ERG1 Potassium Channel / Q000037:antagonists & inhibitors* / Q000737:chemistry; D005419:Flavonoids / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D011485:Protein Binding; D013329:Structure-Activity Relationship
chemical_list: D000975:Antioxidants; D000072237:ERG1 Potassium Channel; D005419:Flavonoids; D026902:Potassium Channel Blockers
keywords: Fisetin; Flavonoids; Quercetin; hERG currents