title: Hesperidin alleviates rat postoperative ileus through anti-inflammation and stimulation of Ca(2+)-dependent myosin phosphorylation.
abstract: OBJECTIVE
  Postoperative ileus (POI) is a postoperative dysmotility disorder of gastrointestinal tract, which remains one of the most perplexing problems in medicine. In the present study we investigated the effects of hesperidin, a major flavonoid in sweet oranges and lemons, on POI in rats.
  
  
  METHODS
  SD rats were administered hesperidin (5, 20, and 80 mg·kg(-1)·d(-1), ig) for 3 consecutive days. POI operation (gently manipulating the cecum for 1 min) was performed on d 2. The gastrointestinal motility and isolated intestinal contraction were examined 1 d after the operation. Then the myosin phosphorylation and inflammatory responses in cecum tissue were assessed. Smooth muscle cells were isolated from rat small intestine for in vitro experiments.
  
  
  RESULTS
  The gastric emptying and intestinal transit were significantly decreased in POI rats, which were reversed by administration of hesperidin. In ileum and cecum preparations of POI rats in vitro, hesperidin (2.5-160 μmol/L) dose-dependently increased the spontaneous contraction amplitudes without affecting the contractile frequency, which was blocked by the myosin light chain kinase (MLCK) inhibitor ML-7 or verapamil, but not by TTX. Furthermore, administration of hesperidin increased the phosphorylation of MLC20 in the cecum tissue of POI rats. Moreover, administration of hesperidin reversed the increased levels of inflammatory cytokines, iNOS and COX-2 in cecum tissue of POI rats. In freshly isolated intestinal smooth muscle cells, hesperidin (5-80 μmol/L) dose-dependently increased the intracellular Ca(2+) concentration as well as the phosphorylation of MLC20, which was abrogated by ML-7 or siRNA that knocked down MLCK.
  
  
  CONCLUSIONS
  Oral administration of hesperidin effectively alleviates rat POI through inhibition of inflammatory responses and stimulation of Ca(2+)-dependent MLC phosphorylation.
authors.affiliation: Central Laboratory, the First Affiliated Hospital, Dalian Medical University, Dalian 116011, China.
authors.forename: Yong-Jian
authors.initials: YJ
authors.lastname: Xiong
authors.affiliation: Dalian Medical University, Dalian 116044, China.
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Chu
authors.affiliation: Dalian Medical University, Dalian 116044, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Laboratory Animal Center, Dalian Medical University, Dalian 116044, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Han
authors.affiliation: Laboratory Animal Center, Dalian Medical University, Dalian 116044, China.
authors.forename: Ya-Chan
authors.initials: YC
authors.lastname: Li
authors.affiliation: Laboratory Animal Center, Dalian Medical University, Dalian 116044, China.
authors.forename: Ai-Guo
authors.initials: AG
authors.lastname: Wang
authors.affiliation: Laboratory Animal Center, Dalian Medical University, Dalian 116044, China.
authors.forename: Fu-Jin
authors.initials: FJ
authors.lastname: Wang
authors.affiliation: Laboratory Animal Center, Dalian Medical University, Dalian 116044, China.
authors.forename: Da-Peng
authors.initials: DP
authors.lastname: Chen
authors.affiliation: Laboratory Animal Center, Dalian Medical University, Dalian 116044, China.
authors.forename: Jing-Yu
authors.initials: JY
authors.lastname: Wang
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D001381:Azepines / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002432:Cecum / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005746:Gastric Emptying / Q000187:drug effects; D005769:Gastrointestinal Motility / Q000187:drug effects; D006569:Hesperidin / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D045823:Ileus / Q000188:drug therapy*; D007249:Inflammation / Q000517:prevention & control*; D007421:Intestine, Small / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D018994:Myosin Light Chains / Q000378:metabolism; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors; D009218:Myosins / Q000378:metabolism*; D009281:Naphthalenes / Q000494:pharmacology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects*; D011183:Postoperative Complications / Q000188:drug therapy; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D014700:Verapamil / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001381:Azepines; D016207:Cytokines; D018994:Myosin Light Chains; D009281:Naphthalenes; D034741:RNA, Small Interfering; C070571:ML 7; D014700:Verapamil; D006569:Hesperidin; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D009219:Myosin-Light-Chain Kinase; D009218:Myosins; D002118:Calcium