Ficus platyphylla alleviates seizure severity and neurobehavioral comorbidities in pentylenetetrazole-kindled rats via modulation of oxidative stress.

PTZ kindling induces oxidative stress, neuronal cell degeneration, and neurobehavioral alterations in rodents that mimic neuropsychiatric comorbidities of epilepsy, which could be initiated or aggravated by some antiepileptic drugs. Here, we investigated the effects of the methanol extract of Ficus platyphylla (FP) on severity scores for seizures, neuronal cell degeneration, and neurobehavioral alterations in rats kindled with pentylenetetrazole (PTZ) and probed the involvement of oxidative stress in these ameliorative effects of FP. FP (50 and 100 mg/kg, p.o.) ameliorated seizure severity, neuronal cell degeneration, depressive behaviors, cognitive dysfunctions, and oxidative stress in rats kindled with PTZ (42.5 mg/kg, i.p.). The findings from this study give additional insights into the potential values of FP in the treatment of persistent epilepsy and major neuropsychiatric comorbidities via modulation of oxidative stress.

In Vivo Anti-Hepatocellular Carcinoma Effects of the Chloroform Root Extract of Clausena excavata Burm.

Liver cancer is the most common cancer among males in Africa. The disease has a poor prognosis and its treatment is associated with toxicity and resistance. For this reason, numerous herbal combinations are being subjected to anticancer screening to circumvent the shortcomings of the conventional anticancer drugs. In the current study, the in vivo anti-cancer effects of the chloroform root extract of the herb, Clausena excavata Burm were investigated. Liver cancer was induced in mice by a single intraperitoneal injection of diethylnitrosamine (DEN) followed by oral administration of the promoter of carcinogenesis, 2-aminoacetyl fluorine that was mixed with the mice feed. The cytotoxicity of the root extract of C. excavata on liver cancer cells was investigated using liver enzyme, histology, DNA fragmentation and caspases assays. Real time qPCR was conducted to evaluate the effect of the extract on apoptotic genes. The findings revealed that the extract of C. excavata significantly decreased the progression of hepatocarcinogenesis and the toxicity-induced production of the liver enzymes, alanine and aspartate aminotransferases. The histological analyses of the liver tissues revealed evidence of apoptotic cell death. The extract also provoked significant (p < .05) expressions of caspase 9 protein and gene as well as other apoptotic genes (P53, P27, Apaf-1, cytochrome C, bax and bid). Therefore, we postulate that the chloroform root extract of C. excavata induces apoptosis of liver cancer in mice.

Studies on neurobehavioural properties of Caralluma dalzielii N.E Br. aqueous aerial parts extract in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Caralluma dalzielii (Asclepiadiaceae) is a shrub used in folkloric medicine to treat epilepsy, pain and infertility in sub-Saharan Africa. Previous studies demonstrated its analgesic, antiulcer, anticonvulsant, and anti-inflammatory activities. AIM: This study aimed to determine the neurobehavioural properties of Caralluma dalzielii aqueous aerial parts extract (CDAE) in mice using standard experimental models. MATERIALS AND METHODS: Neurobehavioural activities of CDAE were evaluated (100, 200, and 400 mg/kg) in Swiss Albino mice using the beam walk, staircase, hole board, object recognition, open field assay, Y-maze and forced swimming tests. Phytochemical constituents were analysed using GC-MS. RESULTS: CDAE significantly increased the mean number of head dips, recognition index and spontaneous alternation in hole board (14.03 at 400 mg/kg and 6.01 in distilled water group; p < 0.05), object recognition (68.16% at 400 mg/kg compared with 51.66% of distilled water group) and Y maze (9.16 at 400 mg/kg as against 4.66 of distilled water group; p < 0.05) tests respectively. It decreased the rearing counts as well as the peripheral and central square crossing in the staircase (4.2 at 400 mg/kg as against 7.87 of the distilled water group; p < 0.05) and open field tests (central, 0.81; peripheral, 1.66 at 400 mg/kg as against central, 5.23; peripheral 11.83 of the distilled water control group; p < 0.05), respectively. There were no significant effects on beam walk assays and forced swim tests. The GC-MS analysis identified a hundred compounds in CDAE. Some compounds which have been reported to possess neurobehavioural activity that were identified include 3,5-Dimethylpyrazole, 2-Amino-5-methylbenzoic acid, Acetophenone, and Tetrahydropyran. CONCLUSION: CDAE demonstrated anxiolytic, anti-hyperactivity, and memory-improving effects in mice. The extract may possess GABAergic and glutamatergic properties. More studies are needed to confirm this. Isolation of the bioactive compounds is currently ongoing to unravel the bioactive constituents present in C. dalzielii extract.

Evaluation of the anti-nociceptive profile of essential oil from Melissa officinalis L. (lemon balm) in acute and chronic pain models.

ETHNOPHARMACOLOGICAL RELEVANCE: Melissa officinalis L. (Lamiaceae) is a medicinal plant native to Mediterranean regions and found in other parts of the world. Extracts and essential oil from this widely cultivated culinary medicinal herb are used in traditional medicine to manage a variety of disorders that include epilepsy and pain. AIM OF THE STUDY: To assess the anti-nociceptive potentials of Melissa officinalis essential oil (MO) and probe the involvement of adrenergic, opioidergic, serotonergic and potassium adenosine triphosphate (KATP) mechanisms in its anti-nociceptive effects. MATERIAL AND METHODS: We employed formalin-, acetic acid and hot plate-induced nociception to study the acute anti-nociceptive effects of MO. The sciatic nerve injury (CCI) model of neuropathic pain was utilized to study the anti-nociceptive effects of MO on chronic pain. Effects of MO on anxiety, cognitive deficits, oxidative stress and inflammation in the CCI rats were evaluated on elevated plus maze, open field test, novel object recognition, oxidative stress parameters and pro-inflammatory cytokines, respectively. The possible mechanism(s) of MO's anti-nociceptive effects were elucidated using prazosin, yohimbine, propranolol, glibenclimide, naloxone and metergoline, which are acknowledged antagonists for α1-, α2- and ß-adrenergic, potassium adenosine triphosphate (KATP), opioidergic and serotonergic systems, respectively. RESULTS: MO significantly attenuated acetic acid- and formalin-induced nociception; prolonged the mean reaction time of rats on hot plate before and following sciatic nerve chronic injury (CCI). MO ameliorated anxiety, cognitive deficits and oxidative stress, reduced pro-inflammatory cytokine levels and produced a near total restoration of injured sciatic nerves in CCI rats. Naloxone, metergoline and glibenclimide significantly blocked, while prazosin, yohimbine and popranolol failed to block the anti-nociceptive effects of MO in formalin-induced nociception. CONCLUSIONS: MO contains biologically active compounds with potential anti-nociceptive properties that modulate KATP, opioidergic and serotonergic pathways. These support the development of bioactive compounds from MO as anti-nociceptive agents.

New Insights Into the Anticonvulsant Effects of Essential Oil From Melissa officinalis L. (Lemon Balm).

Melissa officinalis L. is used in traditional European and Iranian folk medicines to treat a plethora of neurological diseases including epilepsy. We utilized the in vitro and in vivo models of epilepsy to probe the anticonvulsant potentials of essential oil from M. officinalis (MO) to gain insight into the scientific basis for its applications in traditional medicine for the management of convulsive disorders. MO was evaluated for effects on maximal electroshock (MES) and pentylenetetrazole (PTZ) -induced seizures in mice, on 4-aminopyridine (4-AP)-brain slice model of epilepsy and sustained repetitive firing of current clamped neurons; and its ameliorative effects were examined on seizure severity, anxiety, depression, cognitive dysfunction, oxidative stress and neuronal cell loss in PTZ-kindled rats. MO reversibly blocked spontaneous ictal-like discharges in the 4-AP-brain slice model of epilepsy and secondary spikes from sustained repetitive firing, suggesting anticonvulsant effects and voltage-gated sodium channel blockade. MO protected mice from PTZ- and MES-induced seizures and mortality, and ameliorated seizure severity, fear-avoidance, depressive-like behavior, cognitive deficits, oxidative stress and neuronal cell loss in PTZ-kindled rats. The findings warrant further study for the potential use of MO and/or its constituent(s) as adjunctive therapy for epileptic patients.

Methanol extract of Ficus platyphylla decreases cerebral ischemia induced injury in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Extracts of the stem bark of Ficus paltyphylla (FP) are used in the Nigerian traditional medicine to manage psychoses, depression, epilepsy, pain, and inflammation. Our previous studies revealed that the methanol extract of FP ameliorate body core temperature. AIM OF THE STUDY: A number of pharmacological agents that utilize mechanisms that enhanced neuronal survival and/or neural regeneration have been developed for the treatment of stroke. Hypothermia protects the brain from damage caused by ischemia by attenuating destructive processes such as neuroinflammation, excitotoxicity, blood-brain barrier disruption, apoptosis, and free radical formation following cerebral ischemia. In the present study, we examined the neuroprotective potential of FP on permanent occlusion of the middle cerebral artery (MCAO)-induced ischemia in mice. MATERIAL AND METHODS: C57Bl mice were subjected to MCAO. FP was administered 1 h prior to and immediately after surgery. The brains were collected 24 h later and infarct volumes were measured using immune-histochemical staining, DAPI, NeuN, synaptophysin, and NR2B were quantified. RESULTS: Administration of FP prior to MCAO significantly reduced infarct volume, with no effect on infarct volume immediately after MCAO. Higher numbers of cells and neurons were observed in the peri-infarct area in both groups of mice. FP-induced hypothermia protected tissue in the peri-infarct region from synaptophysin reduction. NMDA receptor 2 (NR2B) immunoreactivity is enhanced by MCAO, with no difference observed in both sham-operated and FP-induced hypothermia groups of mice. CONCLUSIONS: The data suggest that FP might be useful in the reduction of ischemia-induced infarct volume when administered prior to the initiation of ischemia with no effect observed after ischemia induction.

Effects of a methanol extract of Ficus platyphylla stem bark on a two-way active avoidance task and on body core temperature.

Preparations of Ficus platyphylla are used in Nigeria's folk medicine to manage a variety of diseases, including insomnia, psychoses, depression, epilepsy, pain, and inflammation. In this study, we examined the effects of the standardised methanol extract of F. platyphylla stem bark (FP) on two-way active avoidance learning and body core temperature to complement earlier studies on the neuroleptic potential of this medicinal plant, which is already in common use. The extract did not interfere with the acquisition and consolidation of the conditioned avoidance reaction (CAR), but did diminish the retrieval of CAR. The extract dose-dependently reduced body core temperature; this was significantly ameliorated by the use of amphetamine. The results confirmed the neuroleptic-like efficacy of FP, probably via the modulation of dopaminergic neurons.

Analgesic potential of standardized methanol stem bark extract of Ficus platyphylla in mice: Mechanisms of action.

ETHNOPHARMACOLOGICAL RELEVANCE: Extracts of the stem bark of Ficus platyphylla (FP) have been used in traditional the Nigerian medicine to treat psychoses, depression, epilepsy, pain and inflammation. Previous studies have revealed the analgesic and anti-inflammatory effects of FP in different assays including acetic acid-induced writhing, formalin-induced nociception, and albumin-induced oedema. PURPOSE/METHODS: In this study, we assessed the effects of the standardised extract of FP on hot plate nociceptive threshold and vocalisation threshold in response to electrical stimulation of the tail root in order to confirm its acclaimed analgesic properties. We also investigated the molecular mechanisms underlying these effects, with the focus on opiate receptor binding and the key enzymes of eicosanoid biosynthesis, namely cyclooxygenase (COX) and 5-lipoxygenase (5-LO). RESULTS: FP (i) increased the hot plate nociceptive threshold and vocalisation threshold. The increase in hot plate nociceptive threshold was detectable over a period of 30min whereas the increase in vocalisation threshold persisted over a period of 90min. (ii) FP showed an affinity for µ opiate receptors but not for δ or κ opiate receptors, and (iii) FP inhibited the activities of COX-2 and 5-LO but not of COX-1. CONCLUSIONS: We provided evidence supporting the use of FP in Nigerian folk medicine for the treatment of different types of pain, and identified opioid and non-opioid targets. It is interesting to note that the dual inhibition of COX-2 and 5-LO appears favourable in terms of both efficacy and side effect profile.

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

Preparations of Ficus platyphylla are used in Nigeria's folk medicine to manage a plethora of diseases including, insomnia, psychoses, depression, epilepsy, pain and inflammation. In this study, we examined the effects of the standardized methanol extract of F. platyphylla stem bark (FP) on apomorphine-induced changes in prepulse inhibition and locomotor activity in rats, as well as on the retrieval of a conditioned reaction in one-way active avoidance in mice. FP did not affect basal prepulse inhibition, but significantly reduced locomotor activity. The apomorphine-induced prepulse inhibition deficit and hyperactivity were significantly reversed by co-administration of clozapine or FP. Furthermore, FP inhibited the retrieval of a conditioned avoidance reaction. Our results revealed that FP contains psychoactive ingredients with neuroleptic-like properties, thus supporting the isolation and development of the biologically active components of this medicinal plant as antipsychotic agents.

Methanol extract of Ficus platyphylla ameliorates seizure severity, cognitive deficit and neuronal cell loss in pentylenetetrazole-kindled mice.

Decoctions of Ficus plathyphylla are used in Nigeria's folk medicine to manage epilepsy for many years and their efficacies are widely acclaimed among the rural communities of Northern Nigeria. In this study, we examined the ameliorative effects of the standardized methanol extract of Ficus platyphylla (FP) stem bark on seizure severity, cognitive deficit and neuronal cell loss in pentylenetetrazole-kindled mice. The (35)S-GTPγS, glutamate and γ-aminobutyric acid receptors binding properties of the extract were also evaluated. Male CD-1 mice were kindled with an initial subeffective dose of pentylenetetrazole (PTZ, 37.5mg/kg, i.p.) for a total of 13 convulsant injections and the treatment groups concurrently received FP (100 and 200mg/kg). Control animals received the same number of saline injections. Twenty-four h after kindling completion the animals' learning performance was tested in a two-way shuttle-box. The animals were challenged with another subeffective dose of PTZ (32.5mg/kg, i.p.) on day 7 after kindling completion. Animals were sacrificed a day after the challenged experiment and the brains were processed for histological investigation. FP ameliorates seizure severity, cognitive deficits and neuronal cell loss in PTZ kindled mice. Components of the extract showed affinity for GABAergic and glutamatergic receptors. Glutamate release was diminished and the (35)S-GTPγS binding assay revealed no intrinsic activity at glutamatergic receptors. Our results revealed that FP contains psychoactive secondary metabolites with anticonvulsant properties, thus supporting the isolation and development of the biologically active components of this medicinal plant as antiepileptic agents.

Behavioral and anticonvulsant effects of the standardized extract of Ficus platyphylla stem bark.

ETHNOPHARMACOLOGICAL RELEVANCE: Decoctions of Ficus platyphylla Del.-Holl (Family: Moraceae) are used in Nigeria׳s folk medicine for the management of epilepsy and their efficacies are widely acclaimed among the rural communities of northern Nigeria. The aim of the study is to examine the behavioral and anticonvulsant properties of the standardized methanol extract of Ficus platyphylla (FP) stem bark, in order to scientifically describe its potential values in the management of convulsive disorders. MATERIALS AND METHODS: High performance liquid chromatography (HPLC) and preliminary phytochemical analysis of the methanol extract were utilized and the intraperitoneal median lethal dose (LD50) determined in mice. The effects of FP were investigated on some murine models of behavior and its anticonvulsant effects studied on pentylenetetrazole (PTZ)-, strychnine (STN)-, picrotoxin (PCT)-, isoniazid (INH)-, aminophylline (AMI)- and maximal electroshock (MES)-induced seizures in mice. RESULTS: The intraperitoneal oral LD50 of FP was estimated to be 5000mg/kg. FP significantly reduced the locomotor activities including the total distance covered, speed, active time and rearing counts. It shortened the onset and prolonged the duration of diazepam-induced sleep, but had no effect on motor coordination on the rota-rod treadmill or beam-walking assay in mice at the doses tested. The extract protected the mice against PTZ- and STN-induced seizures and significantly delayed the latencies of myoclonic jerks and tonic seizures induced by all the standard convulsant agents (PTZ, PCT, INH, STN and AMI) used in this study, but failed to protect the mice against MES seizures at the doses tested. The HPLC fingerprint of the extract shows a spectrum profile characteristic of Ficus platyphylla, while the preliminary phytochemical screening revealed the presence of saponins, flavonoids and tannins. CONCLUSION: Our study provides scientific evidence that FP may contain psychoactive principles with potential anticonvulsant properties, thus supporting further development of the psychoactive components of this plant as anticonvulsant agents.

Ketamine-enhanced immobility in forced swim test: a possible animal model for the negative symptoms of schizophrenia.

Schizophrenia is a chronic and highly complex psychiatric disorder characterised by cognitive dysfunctions, negative and positive symptoms. The major challenge in schizophrenia research is lack of suitable animal models that mimic the core behavioural aspects and symptoms of this devastating psychiatric disorder. In this study, we used classical and atypical antipsychotic drugs to examine the predictive validity of ketamine-enhanced immobility in forced swim test (FST) as a possible animal model for the negative symptoms of schizophrenia. We also evaluated the effects of a selective serotonin reuptake inhibitor (SSRI) on the ketamine-enhanced immobility in FST. Repeated administration of a subanaesthetic dose of ketamine (30 mg kg(-1), i.p., daily for 5 days) enhanced the duration of immobility in FST 24 h after the final injection. The effect, which persisted for at least 21 days after withdrawal of the drug, was neither observed by single treatment with ketamine (30 mg kg(-1) i.p.) nor repeated treatment with amphetamine (1 and 2 mg kg(-1) i.p., daily for 5 days). The enhancing effects of ketamine (30 mg kg(-1) day(-1) i.p.) on the duration of immobility in the FST were attenuated by clozapine (1, 5 and 10 mg kg(-1) i.p.), risperidone (0.25 and 0.5 mg kg(-1) i.p.) and paroxetine (1 and 5 mg kg(-1) i.p.). Haloperidol (0.25 and 0.50 mg kg(-1) day(-1) i.p.) failed to attenuate the ketamine-enhanced immobility in the FST. The repeated ketamine administration neither affects locomotor activity nor motor coordination in rats under the same treatment conditions with the FST, suggesting that the effects of ketamine on the duration of immobility in this study was neither due to motor dysfunction nor peripheral neuromuscular blockade. Our results suggest that repeated treatment with subanaesthetic doses of ketamine enhance the duration of immobility in FST, which might be a useful animal model for the negative symptoms (particularly the depressive features) of schizophrenia.

Anticonvulsant properties of saponins from Ficus platyphylla stem bark.

Preparations of Ficus platyphylla have been used in Nigerian traditional medicine for the management of epilepsy for many years and their efficacy is widely acclaimed among the Hausa communities of northern Nigeria. The anticonvulsant properties of the saponin rich fraction (SFG) obtained from the methanol extract of F. platyphylla stem bark were studied on pentylenetetrazole-, strychnine- and maximal electroshock seizures in mice. Effects of SFG were also examined in murine models for neurological disease and on relevant in vitro targets for anticonvulsant drugs. SFG protected mice against pentylenetetrazole- and strychnine-induced seizures; and significantly delayed the onset of myoclonic jerks and tonic seizures. SFG failed to protect mice against maximal electroshock seizures at doses tested. SFG neither abolished the spontaneous discharges induced by 4-aminopyridine in a neonatal rat brain slice model of tonic-clonic epilepsy nor could it modulate chloride currents through GABA(A) receptor channel complex in cultured cortical cells. However, it was able to non-selectively suppress excitatory and inhibitory synaptic traffic, blocked sustained repetitive firing (SRF) and spontaneous action potential firing in these cultured cells. Our results provide scientific evidence that F. platyphylla stem bark may contain psychoactive principles with potential anticonvulsant properties. SFG impaired membrane excitability; a property shared by most anticonvulsants particularly the voltage-gated sodium channel (VGSC) blocking drugs, thus supporting the isolation and development of the saponin components of this plant as anticonvulsant agents.

Behavioural effect of Pavetta crassipes extract on rodents.

The effects of the ethanol extract of Pavetta crassipes on the central nervous system (CNS) and on actions of some selected centrally acting drugs were studied in mice and rats. These studies were carried out using the spontaneous motor activity (SMA), amphetamine-induced hyperactivity and stereotyped behaviour, pentobarbital-induced hypnosis and exploratory activity, apomorphine-induced climbing and haloperidol-induced catalepsy in rats. The results demonstrated that the extract of P. crassipes dose-dependently decreased SMA in mice and attenuated amphetamine-induced hyperactivity and the different episodes of stereotypic behavioural patterns induced by amphetamine. In addition, the extract decreased the number of head dips in the exploratory activity test and potentiated pentobarbital-induced sleeping time in rats. Furthermore, the extract inhibited apomorphine-induced climbing in mice and potentiated haloperidol-induced catalepsy in rats. Our results suggest that the extract of P. crassipes contains biologically active substance(s) that might be acting centrally through the inhibition of dopaminergic pathway or a system linked to this pathway to mediate the observed pharmacological effects.