Depression continues to be a major global health problem. Although antidepressants are used for its treatment, efficacy is often inconsistent. Thus, the search for alternative therapeutic medicines for its treatment is still important. In this study, the antidepressant-like effect of Pseudospondias microcarpa extract (30–300 mg kg−1, p.o.) was investigated in two predictive models of depression—forced swimming test and tail suspension test in mice. Additionally, the mechanism(s) of action involved were assessed. Acute treatment with the extract dose dependently reduced immobility of mice in both models. The antidepressant-like effect of the extract (100 mg kg−1, p.o.) was blocked by p-chlorophenylalanine and cyproheptadine but not prazosin, propranolol, or yohimbine. Concomitant administration of d-cycloserine and the extract potentiated the anti-immobility effect. In contrast, d-serine, a full agonist of glycine/NMDA receptors, abolished the effects. Anti-immobility effects of PME were prevented by pretreatment of mice with L-arginine (750 mg kg−1, i.p.) and sildenafil (5 mg kg−1, i.p.). On the contrary, pretreatment of mice with L-NAME (30 mg kg−1, i.p.) or methylene blue (10 mg kg−1, i.p.) potentiated its effects. The extract produces an antidepressant-like effect in the FST and TST that is dependent on the serotoninergic system, NMDA receptor complex, and the nitric oxide pathway.
Ethnopharmacological Relevance Mental and neurological disorders are a serious public health challenge globally, particularly in developing countries where cultural factors and limited access to standard healthcare have led to a reliance on traditional medicines. However, ethnopharmacological characterization of traditional medicines used to treat these diseases is lacking. In this study, an ethnobotanical description of plant species used in treating mental and neurological disorders in Ghana and an update of their experimentally validated pharmacological relevance are provided. Materials and Methods Two hundred herbalists agreed to participate but sixty-six specialized in treating mental and neurological disorders were interviewed on their traditional medical practice. Literature review was conducted to verify the experimentally validated pharmacological importance of the reported plants. Results Thirty-two plant species belonging to twenty-eight families were identified. Most plant species had either analgesic (50%), anxiolytic (18.8%), or anticonvulsant (15.6%) properties. Others had reported sedative, anti-Alzheimer's disease, motor coordination, antipsychotic, antidepressant, cognitive enhancement, and neuroprotective properties. While Ageratum conyzoides L. (Asteraceae) and Ocimum gratissimum L. (Lamiaceae) were the most commonly mentioned species with analgesic properties, Lantana camara L. (Verbenaceae) was the most-reported anxiolytic product, with Cymbopogon citratus DC. (Gramineae), Mangifera indica L., Tetrapleura tetraptera Schum Taub. (Fabaceae), and Persea Americana Mill (Lauraceae) being the most studied anticonvulsants. Conclusions This study provides the first report specifically on medicinal plants used in treating mental and neurological disorders in Ghana. Most of the identified plants have been scientifically confirmed to possess neuro- and psychopharmacological properties and may serve as templates for drug development.
Background There is considerable evidence that many people take dietary supplements including those of herbal origin as an alternative therapy to improve their health. One such supplement, with an amalgam of constituents, is CellGevity®. However, the effect of this dietary supplement on drug-metabolizing enzymes is poorly understood, as it has not been studied extensively. Therefore, we investigated the effect of CellGevity dietary supplement on selected rat liver microsomal cytochrome P450 (CYP) enzymes, the most common drug-metabolizing enzymes. We also determined the total antioxidant potential of this dietary supplement in vitro. Methods To determine the antioxidant potential of CellGevity dietary supplement, 2,2-diphenyl-2-picryl-hydrazyl (DPPH), total phenolic, and flavonoid assays were used after initial preparation of a solution form of the supplement (low dose, LD; 4 mg/kg and high dose, HD; 8 mg/kg). Rats received oral administration of these doses of the supplement for 7 days, after which the effect of the supplement on selected liver CYP enzymes was assessed using probe substrates and spectroscopic and high-performance liquid chromatographic methods. Rats which received daily administration of 80 mg/kg of phenobarbitone and distilled water served as positive and negative controls, respectively. Results The IC50 value of the supplement 0.34 ± 0.07 mg/ml compared to 0.076 ± 0.03 mg/ml of the BHT (positive control). The total phenolic content of the supplement at a concentration of 2.5 mg/ml was 34.97 g gallic acid equivalent (GAE)/100 g while its total flavonoid content at a concentration of 2.5 mg/ml was 6 g quercetin equivalent (QE)/100 g. The supplement significantly inhibited rat CYP2B1/2B2 (LDT 92.4%; HDT 100%), CYP3A4 (LDT 81.2%; HDT 71.7%), and CYP2C9 (LDT 21.7%; HDT 28.5%) while it had no significant inhibitory effect on CYPs 1A1/1A2, CYP1A2, and CYP2D6. Conclusion CellGevity dietary supplement possesses moderate antioxidant activity in vitro and has an inhibitory effect on selected rat liver CYP enzymes, suggesting its potential interaction with drugs metabolized by CYP enzymes.
Context:Mallotus oppositifolius is a shrub that is used traditionally to treat epilepsy, but its potential has not been scientifically validated.Aims:This study investigated the anticonvulsant properties and possible mechanism of action of the 70% v/v hydroalcoholic extract of the leaves of M. oppositifolius.Materials and Methods:Inprinting control region (ICR) mice (25–30 g) were pretreated with the M. oppositifolius leaf extract (10–100 mg/kg) before administering the respective convulsants (pentylenetetrazole [PTZ], picrotoxin [PTX], strychnine [STR], 4-aminopyridine [4-AP], and pilocarpine). The effect of the extract in maximal electroshock seizure (MES) model was investigated also.Statistical Analysis:Data were presented as mean ± standard error of the mean and were analyzed with one-way analysis of variance (ANOVA) or two-way ANOVA where appropriate with Newman–Keuls or Bonferroni post hoc test respectively. P < 0.05 was considered significant.Results:In both PTX and PTZ test, extract delayed the onset of seizures and reduced the frequency and duration of seizures. In the STR-induced seizure test, the extract significantly delayed the onset of seizures and reduced the duration of seizures. The extract also delayed the onset of clonic and tonic seizures as well as increasing the survival of mice in the 4-AP-induced seizure test. It further reduced the duration of tonic limb extensions in the MES test. In the pilocarpine-induced status epilepticus, the extract significantly delayed the onset of clonic convulsions and reduced the frequency and duration of seizures. Moreover, the anticonvulsant effect of the extract was attenuated by flumazenil, a benzodiazepine/gamma-aminobutyric acid (GABA) receptor antagonist.Conclusion:These findings show that the extract has anticonvulsant effect possible mediated by GABAergic, glycinergic neurotransmission, and potassium channel conductions. It may also be acting by antagonizing muscarinic receptor activation and N-Methyl-D-aspartate receptor activation.
Natural polymer research has recently become the focus of intensive research in the quest for new enabling excipients for novel drugs in pharmaceutical formulation for optimal treatment outcomes. Evaluations of some excipients have shown deleterious haematological effects of varying extents on the safety profile of these excipients. A 90-day subchronic toxicity study was conducted to evaluate the influence of cocoa pod husk (CPH) pectin on indicators for haematotoxicity. Male and female Sprague Dawley rats (SDRs) were fed with CPH pectin in doses up to 71.4 mg/kg. The effects of CPH pectin on the haematological indices, direct and total bilirubin, and the spleen were determined. The results indicated that CPH pectin did not induce any untoward toxic effects on the haematological indices, bilirubin levels, and the spleen. There were, however, elevations in MCV at day 30, which was not sustained after the 90 days. The data obtained from this study did not reveal any remarkable findings of toxicological relevance to the haematopoietic system.
BackgroundThe hydro-ethanolic whole plant extract of Synedrella nodiflora (SNE) has demonstrated anticonvulsant, sedative and analgesic effects. Preliminary studies conducted in animals, SNE significantly decreased stereotypic behaviours suggesting antipsychotic potential. Coupled with the central nervous system depressant effects of SNE, we hypothesized that it may have utility in the management of psychosis. The present study therefore investigated the antipsychotic potential of the SNE in several murine models of psychosis.MethodThe primary central nervous system activities of SNE (30–3000 mg/kg, p.o) were investigated using the Irwin’s test. The novelty-induced rearing, locomotion and stereotypy counts provoked by SNE (100–1000 mg/kg, p.o) were conducted using the open-field paradigm. The antipsychotic test models used in the screening of SNE (100–1000 mg/kg, p.o) included apomorphine-induced stereotypy, rearing, locomotion and cage climbing activities. The combined effects of a low dose of SNE (100 mg/kg) with various doses of haloperidol and chlorpromazine were analysed using the apomorphine-induced cage climbing and stereotypy, respectively. The ability of SNE to cause catalepsy in naïve mice as well as its effect on haloperidol-induced catalepsy was assessed.ResultsSNE showed acetylcholine-like and serotonin-like activities in the Irwin test, with sedation occurring at high doses. SNE significantly reduced the frequencies of novelty- and apomorphine-induced rearing and locomotion; stereotypy behaviour and the frequency and duration of apomorphine-induced cage climbing in mice. In all the tests performed, SNE was less potent than the reference drugs used (chlorpromazine and haloperidol). In addition, SNE potentiated the effects of haloperidol and chlorpromazine on apomorphine-induced cage climbing and stereotypy activities in mice.ConclusionSNE, while exhibiting antipsychotic properties itself, can also potentiate the antipsychotic effects of chlorpromazine and haloperidol.
Antiaris toxicaria (Moraceae) was evaluated for anticonvulsant activity in rodents. Animal models used include maximal electroshock test (MEST); pentylenetetrazole-induced (PTZ) convulsions; picrotoxin-induced (PCT) convulsions; strychnine- (STR-) and 4-aminopyridine-induced convulsions. Increase in latency to seizures as well as reduction in duration and frequency of seizures indicated anticonvulsant activity. The extract was more effective in all models used except the maximal electroshock test and strychnine-induced convulsions. Antiaris toxicaria aqueous extract (200, 400, and 800 mg kg−1) significantly (P < 0.05 − 0.01) shortened the duration of convulsions in PTZ- and PCT-induced seizures. Delay in the onset of convulsions in the two tests was significant (P < 0.001). Reduction in the frequency of seizures was also significant (P < 0.05 − 0.001) in both tests. Antiaris further delayed the onset of seizures in 4-aminopyridine model while producing 75% protection against death in mice. Diazepam (0.1, 0.3, and 1 mg kg−1), carbamazepine (3, 10, and 30 mg kg−1), and sodium valproate (100–400 mg kg−1) were used as reference anticonvulsant drugs for various models. Flumazenil blocked the effect of the extract in the PTZ test significantly suggesting that Antiaris toxicaria may be acting by enhancing the effects of the GABAergic system. Antiaris toxicaria aqueous extract therefore possesses anticonvulsant activity.
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