title: Mechanism of aqueous fructus aurantii immaturus extracts in neuroplexus of cathartic colons.
abstract: OBJECTIVE
  To examine the effect of aqueous fructus aurantii immaturus (FAI) extracts on the intestinal plexus of cathartic colons.
  
  
  METHODS
  Cathartic colons were induced in rats with dahuang, a laxative used in traditional Chinese medicine. Once the model was established (after approximately 12 wk), rats were administered mosapride (1.54 mg/kg) or various doses of aqueous FAI extracts (1-4 g/kg) for 14 d. Transit function was assessed using an ink propulsion test. Rats were then sacrificed, and the ultramicrostructure of colonic tissue was examined using transmission electron microscopy. The expression of the 5-hydroxytryptamine receptor 4 (5-HTR4) and neurofilament-H was assessed in colon tissues using real-time PCR, Western blot, and immunohistochemistry.
  
  
  RESULTS
  Mosapride and high dose (4 g/kg) of aqueous FAI extracts significantly improved the bowel movement in cathartic colons compared to untreated model colons as measured by the intestinal transit rate (70.06 ± 7.25 and 72.02 ± 8.74, respectively, vs 64.12 ± 5.19; P < 0.05 for both). Compared to controls, the ultramicrostructure of cathartic colons showed signs of neural degeneration. Treatment with mosapride and aqueous FAI extracts resulted in recovery of ultrastructural pathology. Treatment with mosapride alone upregulated the gene and protein expression of 5-HTR4 compared to untreated controls (P < 0.05 for both). Treatment with aqueous FAI extracts (≥ 2 g/kg) increased 5-HTR4 mRNA levels (P < 0.05), but no change in protein level was observed by Western blot or immunohistochemistry. The mRNA and protein levels of neurofilament-H were significantly increased with mosapride and ≥ 2 g/kg aqueous FAI extracts compared to controls (P < 0.05 for all).
  
  
  CONCLUSIONS
  Aqueous FAI extracts and mosapride strengthen bowel movement in cathartic colons via increasing the expression of 5-HTR4 and neurofilament-H.
authors: Shi-Yi Wang, Yan-Ping Liu, Yi-Hong Fan, Lu Zhang, Li-Jun Cai, Bin Lv, Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China.
authors: Shi-Yi
authors: SY
authors: Wang
authors: Shi-Yi Wang, Yan-Ping Liu, Yi-Hong Fan, Lu Zhang, Li-Jun Cai, Bin Lv, Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China.
authors: Yan-Ping
authors: YP
authors: Liu
authors: Shi-Yi Wang, Yan-Ping Liu, Yi-Hong Fan, Lu Zhang, Li-Jun Cai, Bin Lv, Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China.
authors: Yi-Hong
authors: YH
authors: Fan
authors: Shi-Yi Wang, Yan-Ping Liu, Yi-Hong Fan, Lu Zhang, Li-Jun Cai, Bin Lv, Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China.
authors: Lu
authors: L
authors: Zhang
authors: Shi-Yi Wang, Yan-Ping Liu, Yi-Hong Fan, Lu Zhang, Li-Jun Cai, Bin Lv, Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China.
authors: Li-Jun
authors: LJ
authors: Cai
authors: Shi-Yi Wang, Yan-Ping Liu, Yi-Hong Fan, Lu Zhang, Li-Jun Cai, Bin Lv, Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China.
authors: Bin
authors: B
authors: Lv
mesh_terms: D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002400:Cathartics / Q000494:pharmacology*; D003106:Colon / Q000187:drug effects* / Q000294:innervation* / Q000378:metabolism / Q000648:ultrastructure; D003248:Constipation / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D003672:Defecation / Q000187:drug effects; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009197:Myenteric Plexus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology / Q000648:ultrastructure; D009410:Nerve Degeneration; D016900:Neurofilament Proteins / Q000235:genetics / Q000378:metabolism; D008517:Phytotherapy; D010946:Plants, Medicinal; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D044422:Receptors, Serotonin, 5-HT4 / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D001549:Benzamides; D002400:Cathartics; D004365:Drugs, Chinese Herbal; D009025:Morpholines; D016900:Neurofilament Proteins; D012333:RNA, Messenger; C000611371:fructus aurantii immaturus; C051774:neurofilament protein H; D044422:Receptors, Serotonin, 5-HT4; C062720:mosapride
keywords: 5-HTR4; Aqueous extracts; Cathartic colon; Fructus aurantii immaturus; Myenteric plexus; Neurofilament