Clerodendrum inermeLeaf Extract Alleviates Animal Behaviors, Hyperlocomotion, and Prepulse Inhibition Disruptions, Mimicking Tourette Syndrome and Schizophrenia

Abstract

Previously, we found a patient with intractable motor tic disorder, a spectrum of Tourette syndrome (TS), responsive to the ground leaf juice of Clerodendrum inerme (CI). Here, we examined the effect of the ethanol extract of CI leaves (CI extract) on animal behaviors mimicking TS, hyperlocomotion, and sensorimotor gating deficit. The latter is also observed in schizophrenic patients and can be reflected by a disruption of prepulse inhibition of acoustic startle response (PPI) in animal models induced by methamphetamine and NMDA channel blockers (ketamine or MK-801), based on hyperdopaminergic and hypoglutamatergic hypotheses, respectively. CI extract (10–300 mg/kg, i.p.) dose-dependently inhibited hyperlocomotion induced by methamphetamine (2 mg/kg, i.p.) and PPI disruptions induced by methamphetamine, ketamine (30 mg/kg, i.p.), and MK-801 (0.3 mg/kg, i.p.) but did not affect spontaneous locomotor activity, rotarod performance, and grip force. These results suggest that CI extract can relieve hyperlocomotion and improve sensorimotor gating deficit, supporting the therapeutic potential of CI for TS and schizophrenia.

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

“…Although MIH is not an animal model specifically resembling TS/tic disorders, it represents a hyper-dopaminergic status in animals that may mimic several other neurospsychiatric disorders with hyperdopaminergic activity, such as schizophrenia and OCD. Previously, we have demonstrated that haloperidol, a dopamine D2 receptor blocker effective for treating TS/tic clinically although causing extrapyramidal side effects, was effective in the same MIH model (Chen et al, 2012). Hispidulin was effective by i.p.…”

“…CI leaves were collected from mangrove marshes in the riverside of southern Taiwan and stored as reported in our previous study (Chen et al, 2012). A CI leave sample from the same batch was deposited as a voucher specimen (TMU27423) in the herbarium of College of Pharmacy, Taipei Medical University.…”

“…The animal model used is similar to that reported in our previous study (Chen et al, 2012). Male mice (ICR, 6-9 weeks) were housed (3-5 mice per cage) in the holding room on a 12-h/12-h reversed light schedule with free access to rodent chow and water.…”

“…We have found that the ethanol extract of CI effectively alleviated methamphetamineinduced hyperlocomotion (MIH) at doses that did not impair motor functions (Chen et al, 2012). In this study, we further identified the active constituents from the CI ethanol extract using MIH alleviation as a bioassay-guided isolation strategy.…”

Standardized extract of Ficus platyphylla reverses apomorphine-induced changes in prepulse inhibition and locomotor activity in rats

“…Classical and atypical antipsychotics that are clinically used have been shown to selectively inhibit CAR [16]. FP as well as clozapine effectively [41], Catha edulis [42], Glycyrrhiza glabra [43] or Clerodendrum inerme [44] are known to induce PPI deficits in rodents.…”