title: Relaxant effect of flavonoid naringenin on contractile activity of rat colonic smooth muscle.
abstract: BACKGROUND
  Disturbed gastrointestinal (GI) motility can be associated with smooth muscle abnormalities and dysfunction. Exploring innovative approaches that can modulate the disturbed colonic motility are of great importance for clinical therapeutics. Naringenin, a flavonoid presented in many traditional Chinese herbal medicines, has been shown to have a relaxant effect on different smooth muscles. The aim of the present study was to investigate the effect of naringenin on regulation of GI motility.
  
  
  METHODS
  Mechanical recording was used to investigate the effect of naringenin on isolated rat colonic smooth muscle spontaneous contractions. Whole cell patch clamp, intracellular [Ca(2+)] concentration ([Ca(2+)]i) and membrane potential measurements were examined on primary cultures of colonic smooth muscle cells (SMCs). A neostigmine-stimulated rat model was utilized to investigate the effect of naringenin in vivo.
  
  
  RESULTS
  Naringenin induced a concentration-dependent inhibition (1-1000 μM) on rat colonic spontaneous contraction, which was reversible after wash out. The external Ca(2+) influx induced contraction and [Ca(2+)]i increase were inhibited by naringenin (100 μM). In rat colonic SMCs, naringenin-induced membrane potential hyperpolarization was sensitive to TEA and selective large-conductance calcium-activated K(+) (BKCa) channel inhibitor iberiotoxin. Under whole cell patch-clamp condition, naringenin stimulated an iberiotoxin-sensitive BKCa current, which was insensitive to changes in the [Ca(2+)]i concentration. Furthermore, naringenin significantly suppressed neostigmine-enhanced rat colon transit in vivo.
  
  
  CONCLUSIONS
  Our results for the first time demonstrated the relaxant effect of flavonoid naringenin on colon smooth muscle both in vitro and in vivo. The relaxant effect of naringenin was attributed to direct activation of BKCa channels, which subsequently hyperpolarized the colonic SMCs and decreased Ca(2+) influx through VDCC. Naringenin might be of therapeutic value in the treatment of GI motility disorders.
authors.affiliation: The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou 510655, China. Electronic address: yzhuan@mail.sysu.edu.cn.
authors.forename: ZiHuan
authors.initials: Z
authors.lastname: Yang
authors.affiliation: School of Life Science, Sun Yat-sen University, Guangzhou 510275, China.
authors.forename: Ao
authors.initials: A
authors.lastname: Pan
authors.affiliation: School of Life Science, Sun Yat-sen University, Guangzhou 510275, China.
authors.forename: WuLin
authors.initials: W
authors.lastname: Zuo
authors.affiliation: School of Life Science, Sun Yat-sen University, Guangzhou 510275, China.
authors.forename: JingHui
authors.initials: J
authors.lastname: Guo
authors.affiliation: School of Life Science, Sun Yat-sen University, Guangzhou 510275, China. Electronic address: lsszwl@mail.sysu.edu.cn.
authors.forename: WenLiang
authors.initials: W
authors.lastname: Zhou
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D044950:Flavanones / Q000494:pharmacology*; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D066298:In Vitro Techniques; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000819:agonists / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000502:physiology; D009388:Neostigmine / Q000494:pharmacology; D009465:Neuromuscular Agents / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley
chemical_list: D044950:Flavanones; D005765:Gastrointestinal Agents; C494842:Kcnma1 protein, rat; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D009465:Neuromuscular Agents; D009388:Neostigmine; C005273:naringenin; D002118:Calcium
keywords: BK(Ca); Naringenin; Naringenin (PubChem CID: 932); Relaxant effect; Smooth muscle; Spontaneous contraction