Hispidulin, a constituent of Clerodendrum inerme that remitted motor tics, alleviated methamphetamine-induced hyperlocomotion without motor impairment in mice

Wei Jan Huang, Hsin Jung Lee, Hon Lie Chen, Pi Chuan Fan, Yuan Ling Ku, Lih Chu Chiou

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Ethnopharmacological relevance 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. Materials and 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.

Original languageEnglish
Pages (from-to)18-22
Number of pages5
JournalJournal of Ethnopharmacology
Volume166
DOIs
Publication statusPublished - May 26 2015

Fingerprint

Clerodendrum
Tics
Methamphetamine
Tic Disorders
Ethanol
Methylene Chloride
Biological Assay
Protons
Magnetic Resonance Spectroscopy
Rotarod Performance Test
Tourette Syndrome
1-Butanol
Obsessive-Compulsive Disorder
Silica Gel
Locomotion
Crystallization
Flavonoids
Gel Chromatography
Schizophrenia
Motor Activity

Keywords

  • Clerodendrum inerme
  • Flavonoids
  • Hispidulin
  • Methamphetamine
  • Motortics
  • Tourettesyndrome

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

Cite this

Hispidulin, a constituent of Clerodendrum inerme that remitted motor tics, alleviated methamphetamine-induced hyperlocomotion without motor impairment in mice. / Huang, Wei Jan; Lee, Hsin Jung; Chen, Hon Lie; Fan, Pi Chuan; Ku, Yuan Ling; Chiou, Lih Chu.

In: Journal of Ethnopharmacology, Vol. 166, 26.05.2015, p. 18-22.

Research output: Contribution to journalArticle

@article{0416f2d85298454ebdcae73823e3257d,
title = "Hispidulin, a constituent of Clerodendrum inerme that remitted motor tics, alleviated methamphetamine-induced hyperlocomotion without motor impairment in mice",
abstract = "Ethnopharmacological relevance 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. Materials and 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.",
keywords = "Clerodendrum inerme, Flavonoids, Hispidulin, Methamphetamine, Motortics, Tourettesyndrome",
author = "Huang, {Wei Jan} and Lee, {Hsin Jung} and Chen, {Hon Lie} and Fan, {Pi Chuan} and Ku, {Yuan Ling} and Chiou, {Lih Chu}",
year = "2015",
month = "5",
day = "26",
doi = "10.1016/j.jep.2015.03.001",
language = "English",
volume = "166",
pages = "18--22",
journal = "Journal of Ethnopharmacology",
issn = "0378-8741",
publisher = "Elsevier Ireland Ltd",

}

TY - JOUR

T1 - Hispidulin, a constituent of Clerodendrum inerme that remitted motor tics, alleviated methamphetamine-induced hyperlocomotion without motor impairment in mice

AU - Huang, Wei Jan

AU - Lee, Hsin Jung

AU - Chen, Hon Lie

AU - Fan, Pi Chuan

AU - Ku, Yuan Ling

AU - Chiou, Lih Chu

PY - 2015/5/26

Y1 - 2015/5/26

N2 - Ethnopharmacological relevance 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. Materials and 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.

AB - Ethnopharmacological relevance 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. Materials and 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.

KW - Clerodendrum inerme

KW - Flavonoids

KW - Hispidulin

KW - Methamphetamine

KW - Motortics

KW - Tourettesyndrome

UR - http://www.scopus.com/inward/record.url?scp=84925386100&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84925386100&partnerID=8YFLogxK

U2 - 10.1016/j.jep.2015.03.001

DO - 10.1016/j.jep.2015.03.001

M3 - Article

C2 - 25764963

AN - SCOPUS:84925386100

VL - 166

SP - 18

EP - 22

JO - Journal of Ethnopharmacology

JF - Journal of Ethnopharmacology

SN - 0378-8741

ER -