Abstract:
Tics
are characterized by involuntary, sudden, rapid, repetitive, nonrhythmic,
stereotyped movements or phonic productions. Those who suffer from
either motor or phonic tics, but not both, for more than 1 year are
diagnosed with chronic tic disorder. Several pharmacological
interventions have been proposed for the treatment of tic disorder.
Dopamine D2 receptor blockers and dopamine depletors are thought to be
the most effective ones clinically. However, such treatments are
suboptimal in terms of effectiveness and side effects, such as body
weight gain and extrapyramidal symptoms. We report on a 13-year-old
girl, with chronic motor tic disorder refractory to multiple anti-tic
therapies, who showed dramatic improvement and remission after taking
the crude leaf extract of Clerodendrum inerme (L) Gaertn. No side
effects were observed during a follow-up of more than 2 years. To the
best of our knowledge, this is the first report on the anti-tic effect
of Clerodendrum inerme.
Hispidulin, a
constituent of
Clerodendruminerme
that remitted motor tics, alleviated methamphetamine-induced hyperlocomotion
without motor impairment in mice.
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.
Tic Disorders 3 -
Types of Tics (7:39 minutes)
Tic Disorders 7 - PANDAS (4:58 minutes)
Clerodendrum
Inerme (Cleo)
Homeopathic Remedy for Tics and Tourettes
(14:02 minutes)
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