Revealing the most effective anticonvulsant part of Malvaviscus arboreus Dill. Ex Cav. and its acute and sub-acute toxicity.

ETHNOPHARMACOLOGY RELEVANCE: Different parts of Malvaviscus arboreus Dill. Ex Cav. (M. arboreus) are traditionally used in the West Region of Cameroon to treat many diseases, including epilepsy. AIM OF THE STUDY: To determine which part of M. arboreus offers the best anticonvulsant effect, and to assess the acute and sub-acute toxicity of the part of interest. MATERIALS AND METHODS: the anticonvulsant effect of the aqueous lyophilisate of the decoction of flowers, leaves, stems and roots of M. arboreus at various doses was evaluated and compared on the model of acute epileptic seizures induced by pentylenetetrazole (PTZ) (70 mg/kg), injected 1 h after oral administration of the various extracts. Out of these plant parts, the leaves were then selected to prepare the hydroethanolic extract and its anticonvulsant effect against PTZ at the doses of 122.5, 245 and 490 mg/kg, as well as its acute toxicity were compared with those of the aqueous lyophilisate of the leaves. The anticonvulsant effect of the aqueous lyophilisate of M. arboreus leaves was further evaluated on models of acute epileptic seizures induced by picrotoxin (PIC) (7.5 mg/kg), strychnine (STR) (2.5 mg/kg) and pilocarpine (350 mg/kg). The 28 days sub-acute toxicity, as well as the quantitative phytochemistry and the in vitro antioxidant potential (FRAP, DPPH, ABTS+) of the aqueous lyophilisate of the leaves of M. arboreus were also evaluated. RESULTS: M. arboreus leaves showed the best anticonvulsant effect and the aqueous lyophilisate was the best extract. The latter significantly protected the animals against convulsions induced by PTZ (71.43%) (p < 0.01), PIC (57.14%) (p < 0.05) and STR (42%) and had no effect on pilocarpine-induced seizures. Furthermore, it showed no acute or sub-acute toxicity, and revealed a high content of flavonoids, saponins, tannins and alkaloids, and antioxidant activity in vitro. CONCLUSION: The aqueous lyophilisate of the leaves of M. arboreus offers the best anticonvulsant effect on the extraction solvent used, and it would act mainly via a potentiation of the inhibitory systems of the brain (GABA, Glycine). In addition, its richness in bioactive compounds gives it an antioxidant potential, and it is not toxic in acute and sub-acute toxicity. All this justifies at least in part its empirical uses, and makes M. arboreus a candidate for the alternative treatment of epilepsy.

Pharmacological and toxicological effects of Ruta chalepensis L. on experimentally induced seizures and electroencephalographic spectral power in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Ruta chalepensis L. (Rutaceae) is used in traditional medicine to treat a wide variety of disorders such as rheumatism, fever, mental disorders, dropsy, neuralgia, menstrual problems, anxiety, and epilepsy. AIM OF THE STUDY: To evaluate and compare the anticonvulsant properties of an aqueous extract and ethyl acetate (AcOEt) fraction of R. chalepensis on pentylenetetrazole (PTZ)-induced seizures and maximal electroshock (MES) test in mice, by analyzing behavior and electroencephalogram (EEG), as well as GABAA receptors involvement. METHODS: The effect of an acute administration of different dosage of the aqueous extract (300 or 500 mg/kg) or AcOEt fraction (100, 300, 500 or 1000 mg/kg) of R. chalepensis was explored on two different models of acute seizure induction in mice, the PTZ and maximal electroshock (MES) tests. Behavioral and electrographic effects were quantified. Additionally, the possible involvement of the GABAA receptors was explored in the presence of picrotoxin (a non-competitive antagonist of the GABAA receptor). RESULTS: AcOEt fraction of R. chalepensis was more efficient than aqueous extract to reduce the incidence of tonic-clonic seizures and mortality in a significant and dose-dependent manner in both the PTZ and MES tests. This anticonvulsant effect was not abolished in the presence of picrotoxin. The EEG spectral power analysis revealed that aqueous extract decreased alpha and beta power, while AcOEt fraction decreased alpha and gamma power confirming previous findings of its depressant effect in the central nervous system. It is important to mention that the highest dosage of the AcOEt (1000 mg/kg) produced a severe suppression or isoelectric EEG activity (EEG flattening), recognized as a comatose state, suggesting a neurotoxic effect at this dosage. CONCLUSION: Our data reinforce that depressant and anticonvulsant effects of R. chalepensis depend in part on the presence of constituents from medium polarity. We also found that anticonvulsant effect is not mediated by GABAA receptors. In addition, cautious is emphasized when high doses of this natural product are used in traditional medicine since it might produce neurotoxic effects.

Anticonvulsant activity of DNS II fraction in the acute seizure models.

AIM OF THE STUDY: Delphinium nordhagenii belongs to family Ranunculaceae, it is widely found in tropical areas of Pakistan. Other species of Delphinium are reported as anticonvulsant and are traditionally used in the treatment of epilepsy. Delphinium nordhagenii is used by local healer in Pakistan but never used for scientific investigation as anticonvulsant. Thus, Delphinium nordhagenii was subjected to bioassay-guided fractionation and the most active fraction, i.e. DNS II acetone was chosen for further testing in the acute seizure models of epilepsy to study the antiepileptic potential in male mice. MATERIALS AND METHODS: Different doses (60, 65 and 70mg/kg, i.p.) of DNS II acetone fraction of Delphinium nordhagenii was administered 30min prior the chemoconvulsant's injection in the male mice. Convulsive doses of chemoconvulsants (pentylenetetrazole 90mg/kg, s.c. and picrotoxin 3.15mg/kg, s.c.) were used. The mice were observed 45-90min for the presence of seizures. Moreover, four different doses of DNS II (60, 65, 70 and 100mg/kg, i.p.) were tested in the MES test. RESULTS: The DNS II acetone fraction of Delphinium nordhagenii has exhibited the anticonvulsant actions by preventing the seizures against PTZ- and picrotoxin-induced seizure as well as 100% seizure protection in MES test. The results are comparable with standard AEDs (diazepam 7.5mg/kg, i.p. and phenytoin 20mg/kg, i.p.). CONCLUSIONS: These findings suggest that the Delphinium nordhagenii possesses the anticonvulsant activity. Further analysis is needed to confirm the structure and target the extended activity profile.

'Complementary ENT': a systematic review of commonly used supplements.

OBJECTIVE: To assess the evidence surrounding the use of certain complementary supplements in otolaryngology. We specifically focussed on four commonly used supplements: spirulina, Ginkgo biloba, Vertigoheel and nutritional supplements (cod liver oil, multivitamins and pineapple enzyme). MATERIALS AND METHODS: A systematic review of the English and foreign language literature. INCLUSION CRITERIA: in vivo human studies. EXCLUSION CRITERIA: animal trials, in vitro studies and case reports. We also excluded other forms of 'alternative medicine' such as reflexology, acupuncture and other homeopathic remedies. RESULTS: Lack of common outcome measures prevented a formal meta-analysis. Three studies on the effects of spirulina in allergy, rhinitis and immunomodulation were found. One was a double-blind, placebo, randomised, controlled trial (RCT) of patients with allergic rhinitis, demonstrating positive effects in patients fed spirulina for 12 weeks. The other two studies, although non-randomised, also reported a positive role for spirulina in mucosal immunity. Regarding the use of Ginkgo biloba in tinnitus, a Cochrane review published in 2004 showed no evidence for this. The one double-blind, placebo-controlled trial that followed confirmed this finding. Regarding the use of Vertigoheel in vertigo, two double-blind RCTs and a meta-analysis were identified. The first RCT suggested that Vertigoheel was equally effective in reducing the severity, duration and frequency of vertigo compared with betahistine. The second RCT suggested that Vertigoheel was a suitable alternative to G. biloba in the treatment of atherosclerosis-related vertigo. A meta-analysis of only four clinical trials confirms that Vertigoheel was equally effective compared with betahistine, G. biloba and dimenhydrinate. Regarding multivitamins and sinusitis, two small paediatric pilot studies reported a positive response for chronic sinusitis and otitis media following a course of multivitamins and cod liver oil. Regarding bromelain (pineapple enzyme) and sinusitis, one randomised, multicentre trial including 116 children compared bromelain monotherapy to bromelain with standard therapy and standard therapy alone, for the treatment of acute sinusitis. The bromelain monotherapy group showed a faster recovery compared with the other groups. CONCLUSION: The positive effects of spirulina in allergic rhinitis and of Vertigoheel in vertigo are based on good levels of evidence, but larger trials are required. There is overwhelming evidence that G. biloba may play no role in tinnitus. There is limited evidence for the use of multivitamins in sinus symptoms, and larger randomised trials are required.

Microcirculatory effects of a homeopathic preparation in patients with mild vertigo: an intravital microscopic study.

The effects of the homeopathic preparation Vertigoheel on variables related to microcirculation were investigated using vital microscopy techniques in patients with vestibular vertigo. In a non-randomized, open study, 16 patients given Vertigoheel were compared with 16 untreated patients. Measurements were carried out in two areas (defined by selecting 60 blood-cell perfused nodal points of arterioles, venules, and capillaries with a mean diameter > or = 40 microm): the cuticulum/subcuticulum of the inside left lower arm and an area 5 mm behind the left earlobe. After 12 weeks of treatment, patients receiving the homeopathic preparation exhibited an increased number of nodal points, increased flow rates of erythrocytes in both arterioles and venules, increased vasomotion, and a slight reduction in hematocrit vs. baseline. None of these changes were observed in the control group and the differences between treatment groups were statistically significant. Partial oxygen pressure increased significantly in the Vertigoheel group compared with the control group. In addition, in Vertigoheel patients, significantly increased numbers of cell-wall adhering leucocytes were observed, accompanied by increased local concentrations of the adhesion molecules ICAM-1. The microcirculatory changes were associated with a reduction in the severity of vertigo in the actively treated patients, both as assessed by the treating physician and by the patients themselves. The data support a pharmacological effect on microcirculation from the treatment.

The homeopathic preparation Vertigoheel versus Ginkgo biloba in the treatment of vertigo in an elderly population: a double-blinded, randomized, controlled clinical trial.

OBJECTIVE: Alternative medical practices are common in the treatment of vertigo. This study compared the effects of Ginkgo biloba treatment with the homeopathic remedy Vertigoheel (Biologische Heilmittel Heel GmbH, Baden-Baden, Germany). DESIGN: Randomized, double-blinded, parallel group study. SUBJECTS: One hundred and seventy (170) patients, ages 60-80 years, with atherosclerosis-related vertigo. INTERVENTIONS: Patients were randomly allocated to receive treatment with either Vertigoheel (n = 87) or G. biloba (n = 83). OUTCOME MEASURES: The results were analyzed for the non-inferiority of Vertigoheel to G. biloba on the combined endpoint of changes from baseline to week 6 in dizziness score (assessed by questionnaire), frequency, duration, and intensity of vertigo episodes (recorded in patient diaries). RESULTS: Both treatments improved vertigo status. From a baseline mean value of 26.1 +/- 5.2 (on a 50-point scale) in the Vertigoheel group, the dizziness questionnaire score improved by -10.6 +/- 10.0, and by -10.7 +/- 9.0 from 25.8 - 4.7 in the G. biloba group. Statistical analysis of this endpoint showed that Vertigoheel was not inferior to G. biloba. The 95% confidence interval for the difference between treatment did not reach the inferiority threshold of 0.36 at any of the time points tested. The results were supported by the results of a line walking test, Unterberger's stepping test, and patient and physician global assessments of therapeutic effect. Both treatments were well tolerated. CONCLUSIONS: Vertigoheel is an appealing alternative to established G. biloba therapy for atherosclerosis-related vertigo.

Treatment of vertigo with a homeopathic complex remedy compared with usual treatments: a meta-analysis of clinical trials.

The increasing interest in alternative medical practices has led to a number of controlled studies on herbal and homeopathic agents. This paper presents the results of a meta-analysis of four recent clinical trials evaluating the homeopathic preparation Vertigoheel (VH) compared with usual therapies (betahistine, Ginkgo biloba extract, dimenhydrinate) for vertigo in a total of 1388 patients. Two trials were observational studies and the other two were randomised double-blind controlled trials. The duration of treatment (6-8 weeks) and dosage were comparable in all studies. Treatments were evaluated for the variables "number of vertigo episodes", "intensity of episodes" and "duration of episodes". As the studies differed in the age of patients and in the baseline values of vertigo, the individual reductions of number, intensity and duration of episodes were adjusted on equal age and baseline values (total means). An analysis of variance (with studies as random effects) showed no relevant influence of studies on the adjusted reductions and no relevant interaction between studies and treatment effects. The meta-analysis of all four trials showed equivalent reductions with VH and with control treatment: mean reduction of the number of daily episodes 4.0 for VH and 3.9 for control (standard error 0.11 for both groups); mean reduction of the duration (on a scale 0-4) for VH 1.1 and for the control 1.0 (standard error 0.03 for both groups); mean reduction of the intensity (on a scale 0-4) for VH 1.18 and for the control 1.8 (standard error 0.03 for both groups). In the non-inferiority analysis from all trials, VH was non-inferior in all variables. The results show the applicability of meta-analyses on the data from studies with homeopathicdrugs and support the results from the individual studies indicating good efficacy and tolerability of VH in patients with vertigo.

Suppression of absence seizures by electrical and pharmacological activation of the caudal superior colliculus in a genetic model of absence epilepsy in the rat.

Activation of the superior colliculus has been shown to reproduce the antiepileptic effect of the inhibition of the substantia nigra reticulata. A circuit involving neurons of the caudal deep layers of the superior colliculus has been suggested to control brain stem convulsive seizures. The present study was designed to examine whether a similar circuit is also involved in the control of absence seizures. For this, activation of either the rostral or caudal parts of the deep and intermediate layers of the superior colliculus was applied in a genetic model of absence seizures in the rat (GAERS). Single-shock (5 s) electrical stimulation of the rostral and caudal superior colliculus interrupted ongoing spike-and-wave discharges at an intensity (antiepileptic threshold) significantly lower than the intensity inducing behavioral effects. At this intensity, no interruption of licking behavior was observed in water-deprived rats. Repeated stimulations (5 s on/5 s off) at the antiepileptic threshold reduced absence seizures only during the first 10 min. Bilateral microinjection of a GABA antagonist (picrotoxin, 33 pmol/side) significantly suppressed spike-and-wave discharges when applied in the caudal aspect of the superior colliculus. This antiepileptic effect appears dissociated from an anxiogenic effect, as tested in an elevated plus maze test. Finally, bilateral injection of picrotoxin (33 pmol/side) appeared more effective in the superficial and intermediate layers of the caudal superior colliculus, whereas such injections had only weak effects on absence seizures when applied in the deep layers. These results suggest that a specific population of neurons located in the intermediate and superficial layers of the caudal superior colliculus is involved in the inhibitory control of absence seizures. It may constitute an important relay for the control of absence seizures by the basal ganglia via the substantia nigra reticulata.

[Myogenic vestibular evoked potentials used to objective estimation of effectiveness of central action drugs]. / Miogenne przedsionkowe potencjaly wywolane zastosowane jako obiektywna ocena skutecznosci leków o dzialaniu osrodkowym.

In this paper possibility of employing vestibular evoked myogenic potentials (VEMPs) was evaluated to following efficacy of drug effect in patients with central and peripheral vestibular disorders of various aetiologies. Also influence of antihomotoxic remedies on sacculo-collic reflex function were followed. Treatment concerned 23 ills that is 20 women and 3 men in age from 20 to 68 years, average age being 46,82 years. The studied population included 8 patients were diagnosed to have Meniere's disease, 5 ills suffered from neuronitis vestibularis, 5 patients complained of vertigo of vertebrobasilar arterial insufficiency. 3 patients were diagnosed to have vertigo after head trauma, 1 patient suffered from benign paroxysmal positional vertigo and one's cause of disease was unknown. Patients with tumor of ponto-cerebellaris angle or VIII nerve were excluded. Registration of VEMPs was done in all patients treated before starting and after stopping therapy. After using of Cerebrum comp. improvement of vestibulo-spinal reflex function was affirmed in the form of shorted latencies and higher amplitudes of VEMPs in the most patients. Using sublingually of Vertigoheel distinct greater amplitudes were observed in significant numbers of patients after therapy. Administered of placebo did not essential influence on values of VEMPs parameters.

The clinical efficacy of Vertigoheel in the treatment of vertigo of various etiology.

In this paper the authors describe the clinical efficacy in treatment of vertigo of various etiology. A group of 31 patients were treated with Vertigoheel medication: 14 patients suffered from vertebrobasilar arterial insufficiency, 8 patients were diagnosed as Meniere's disease, 5 patients complained of vertigo of traumatic origin and 4 patients suffered from neuronitis vestibularis. The authors found regression of clinical symptoms in the majority of cases in the investigated group who were treated with Vertigoheel.

[Inhibitory effects of gamma-aminobutyric acid and diazepam on ventricular arrhythmias induced by hypothalamic electric stimulation].

The experiments were carried out on rabbits with ventricular arrhythmias (VA) induced by hypothalamic electric stimulation. The effects of GABA or diazepam (Dz) and picrotoxin on VA were observed. After GABA 0.25, 0.5, 1 mg/rabbit were injected into cerebral ventricle (icv) or cisterna magna (icm), the VA was dose-dependently reduced, the similar effect was seen after Dz 0.1 mg was injected into subarachnoid cavity (sac) or icm. The effect was not induced by GABA sac or Dz icv. Picrotoxin 20 micrograms icv or 30 micrograms icm obviously increased VA, and this effect was partly antagonized by pretreatment with GABA 0.5 mg icv or icm and Dz 0.1 mg icm. The results suggest that central GABAergic system plays an important role in development of arrhythmias, and that increasing activity in this system may inhibit VA.

[Clinical experimental test and equilibrimetric measurements of the therapeutic action of a homeopathic drug consisting of ambra, cocculus, Conium and mineral oil in the diagnosis of vertigo and nausea]. / Klinisch-experimentelle Prüfung und äquilibriometrische Messungen zum Nachweis der therapeutischen Wirksamkeit eines homöopathischen Arzneimittels bestehend aus Ambra, Cocculus, Conium und Petroleum bei der Diagnose Vertigo und Nausea.

This paper presents a study by means of a modern neurotological technique for investigating the action and the site of action of an antivertiginous drug. The sensory motor tests are able to discriminate the sites of the lesions in the equilibrium regulating system, i.e., peripheral vestibular system, lower brainstem regulating system, upper brainstem nystagmus generating system and supratentorial system. Acoustic brainstem evoked potentials add information. A sample of 40 vertigo and nausea patients was treated by a combined drug, containing cocculus D4 210 mg, conium D3 30 mg, ambra D6 30 mg, mineral oil D8 30 mg (Vertigo-heel). The patients received 3 tablets 3 times per day during 14 days. An initial investigation was performed just before starting the treatment. A second directly followed the therapy. By subjective self-rating 57.5% of the patients reported on an improvement after the intake of Vertigoheel. Statistical evaluations showed that the different vertigo and nausea symptoms as well as the trigger mechanisms of vertigo and nausea (i.e. getting up, turning the head or gazing aside), highly significantly improved due to the therapy. The objective sensory motor tests showed a highly significant improvement in the monaural caloric butterfly chart as well as in the vestibulospinal head and body sway. The site of the action of Vertigoheel is in the brainstem and the Medulla oblongata, especially the middle longitudinal fascicle (MLF). The localisation in this area can be stressed by the investigation with acoustically brainstem evoked potentials (ABEP).(ABSTRACT TRUNCATED AT 250 WORDS)