title: Hispidulin, a constituent of Clerodendrum inerme that remitted motor tics, alleviated methamphetamine-induced hyperlocomotion without motor impairment in mice.
abstract: BACKGROUND
  Previously, we found a patient with an intractable motor tic disorder that could be ameliorated by the ground leaf juice of Clerodendrum inerme (CI). Furthermore, the ethanol extract of CI leaves effectively ameliorated methamphetamine-induced hyperlocomotion (MIH) in mice, an animal model mimicking the hyper-dopaminergic status of tic disorders/Tourette syndrome, schizophrenia, or obsessive-compulsive disorder. Here, we for the first time identified a constituent able to reduce MIH from the CI ethanol extract that might represent a novel lead for the treatment of such disorders.
  
  
  METHODS
  The ethanol extract of CI was sub-divided into n-hexane, dichloromethane, n-butanol and water fractions. Using MIH alleviation as a bioassay, active compounds were identified in these fractions using silica gel chromatography, recrystallization and proton NMR spectroscopy.
  
  
  RESULTS
  The dichloromethane and n-hexane fractions were active in the bioassay. Further subfractionation and re-crystallization resulted in an active compound that was identified to be hispidulin by proton NMR spectroscopy. Hispidulin significantly alleviated MIH in mice at doses that did not affect their spontaneous locomotor activity or performance in the rotarod test, a measure for motor coordination.
  
  
  CONCLUSIONS
  Hispidulin is a flavonoid that has been isolated from several plants and reported to have anti-oxidative, anti-inflammatory and anti-cancer activities. Here, we for the very first time found that hispidulin can also alleviate MIH at doses that did not impair motor activity, suggesting a therapeutic potential of hispidulin in hyper-dopaminergic disorders.
authors.affiliation: Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei, Taiwan; School of Pharmacy, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Wei-Jan
authors.initials: WJ
authors.lastname: Huang
authors.affiliation: Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Hsin-Jung
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Hon-Lie
authors.initials: HL
authors.lastname: Chen
authors.affiliation: Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Pediatrics, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Pi-Chuan
authors.initials: PC
authors.lastname: Fan
authors.affiliation: Medical and Pharmaceutical Industry Technology and Development Center, New Taipei City, Taiwan.
authors.forename: Yuan-Ling
authors.initials: YL
authors.lastname: Ku
authors.affiliation: Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei, Taiwan. Electronic address: lcchiou@ntu.edu.tw.
authors.forename: Lih-Chu
authors.initials: LC
authors.lastname: Chiou
mesh_terms: D000818:Animals; D032409:Clerodendrum / Q000737:chemistry*; D020834:Ethnopharmacology / Q000379:methods; D047309:Flavones / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects*; D008517:Phytotherapy / Q000379:methods; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology
chemical_list: D047309:Flavones; D010936:Plant Extracts; D008694:Methamphetamine; C055957:hispidulin
keywords: Acacetin (PubChem CID: 5280442); Clerodendrum inerme; Flavonoids; Hispidulin; Hispidulin (PubChem CID: 5281628); Methamphetamine; Motor tics; Tourette syndrome