title: Lipopolysaccharide increased the acute toxicity of the Rhizoma coptidis extract in mice by increasing the systemic exposure to Rhizoma coptidis alkaloids.
abstract: BACKGROUND
  Rhizoma coptidis is used as an antidysenteric in clinics in China. However, patients suffering from dysentery are susceptible to the acute toxicity of Rhizoma coptidis. The current study investigates the effects of lipopolysaccharide (LPS), which are a key pathogenic factor in dysentery, on the acute toxicity of a Rhizoma coptidis extract in mice; possible mechanisms are proposed.
  
  
  METHODS
  Acute toxicity and pharmacokinetic experiments in mice were conducted. The plasma concentration of Rhizoma coptidis alkaloids in mice was determined using liquid chromatography/tandem mass spectrometry. The activity of acetylcholinesterase (AChE) in the tissue homogenate was determined using an AChE determination kit.
  
  
  RESULTS
  Pretreatment with LPS for 16 h increased the acute toxicity of the oral Rhizoma coptidis extract. Systemic exposure to Rhizoma coptidis alkaloids was also increased by LPS pretreatment. Neostigmine significantly increased whereas pyraloxime methylchloride reduced the acute toxicity of the Rhizoma coptidis extract. LPS pretreatment alone showed no significant effect on the activity of thoracoabdominal diaphragm AChE. However, it enhanced the inhibitory effect of the Rhizoma coptidis extract. LPS pretreatment did not affect the acute toxicity of various dosages of tail vein-injected berberine.
  
  
  CONCLUSIONS
  LPS increased the acute toxicity of the oral Rhizoma coptidis extract in mice by increasing the systemic exposure to the Rhizoma coptidis alkaloids.
authors.affiliation: Laboratory of Pharmacokinetics, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Bing-Liang
authors.initials: BL
authors.lastname: Ma
authors.forename: Yue-Ming
authors.initials: YM
authors.lastname: Ma
authors.forename: Cheng-Lu
authors.initials: CL
authors.lastname: Gao
authors.forename: Jia-Sheng
authors.initials: JS
authors.lastname: Wu
authors.forename: Fu-Rong
authors.initials: FR
authors.lastname: Qiu
authors.forename: Chang-Hong
authors.initials: CH
authors.lastname: Wang
authors.forename: Xin-Hong
authors.initials: XH
authors.lastname: Wang
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D001599:Berberine / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity*; D002800:Cholinesterase Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity*; D039323:Coptis / Q000737:chemistry* / Q000633:toxicity; D000089042:Coptis chinensis; D004334:Drug Administration Schedule; D004365:Drugs, Chinese Herbal / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity*; D004403:Dysentery / Q000188:drug therapy*; D005260:Female; D008070:Lipopolysaccharides / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009388:Neostigmine / Q000494:pharmacology; D008517:Phytotherapy; D027343:Rhizome
chemical_list: D002800:Cholinesterase Inhibitors; D004365:Drugs, Chinese Herbal; D008070:Lipopolysaccharides; D001599:Berberine; D009388:Neostigmine; C107393:Coptidis rhizoma extract; D000110:Acetylcholinesterase