Mucuna pruriens seed protects the hippocampal neurons and abrogates seizure indices in chemically-convulsed mice: Evidence of the Nrf2 expression defense pathway.

The anti-convulsant mechanisms and neuroprotective effects of Mucuna pruriens (MP) seed in male BALB/c mice were evaluated. Ninety mice were kindled with picrotoxin, strychnine, or pilocarpine hydrochloride at the 30th minute of intraperitoneal injection (i.p) of normal saline (0.2 ml), MP (200, 100, 50 mg/kg), diazepam (7.5 mg/kg), or haloperidol (5 mg/kg). The onset of convulsion and percentage mortality was recorded. The histoarchitectural and immunohistochemical profiles of the brains were determined. Data were expressed as mean ± SEM with a one-way analysis of variance (ANOVA), while p < 0.05 was considered significant. There was a significant prolongation of the latency to first seizure across the treatment groups following picrotoxin, and pilocarpine-induced convulsion; a decrease in percentage mortality in the MP (50 mg/kg) treatment group, and an increase in the hippocampal nuclear factor erythroid 2-related factor 2 count, and Neu-N expression in the MP (200 mg/kg, and 100 mg/kg) treated mice. Treatment with MP seed may abolish seizure occurrence and consequential mortality; mechanisms traceable to its GABAergic expression and hippocampal NRF 2 and Neu N expression.

Preliminary assessment of proanthocyanidin isolates of Vitis vinifera seed on the central nervous system of male Albino mice.

This study evaluated the potential neurobehavioral effects of proanthocyanidin-rich-fraction (PRF) obtained from Vitis vinifera seed in male Albino mice. Adult (2½- to 3-month old) male Albino mice were treated with PRF (200, 100, 50 mg/kg) and subjected to diverse behavioral models specially designed for the assessment of central nervous system-acting agents. One-shot intraperitoneal (i.p) injection of PRF (200 and 100 mg/kg) decreased the rectal temperature, exploratory activities (locomotion, rearing, and grooming), anxiety-like responses (% open-arm time, open-arm entries but decreased the total number of enclosed arm times). However, acute i.p administration of PRF decreased the total score of apomorphine-induced stereotyped behaviors, latency to hexobarbitone-induced sleep, and increased the total sleep duration. Moreover, indices of convulsion (tonic flexion, extension, clonic convulsion, stupor, and recovery time) were decreased in the PRF treatment groups, especially the PRF (50 mg/kg)-treated mice. Based on these present findings, it could therefore be inferred that systemic administration of PRF of V. vinifera seed origin induces diverse modification on the behaviors of the treated mice stemming from anxiolytic, anticonvulsant, sedative, and decrease in core temperature.

Graded doses of grape seed methanol extract attenuated ataxic movement, cerebellocortical toxicity, and impairment following chronic carbamazepine treatment in male Wistar rats.

This study investigated the effects of chronic cotreatment of carbamazepine (CBZ) with grape seed methanolic extract (GSME) on the markers of neurotoxicity and motor coordination in male rats. Thirty male Wistar rats were randomized into 5 groups (n = 6) and treated orally with propylene glycol (PG 0.1 ml/day), CBZ (25 mg/kg), CBZ (25 mg/kg) + GSME (200 mg/kg), CBZ (25 mg/kg) + GSME (100 mg/kg), or CBZ (25 mg/kg) + GSME (50 mg/kg) for 28 days. Thereafter, the animals were subjected to motor-coordination tests and, eventually, sacrificed by cervical dislocation. The cranium was opened and the brain excised. The prefrontal cortex (PFC) and cerebellum were homogenized for the biochemical assessment, while representative brain was fixed in 10% neutral-buffered formalin for the histomorphological investigation. The results were presented as mean ±â€¯SEM, analyzed using one-way analysis of variance (ANOVA) and Student-Newman-Keuls post hoc analysis where appropriate, while p < 0.05 was considered statistically significant. Indices of motor coordination were significantly (p = 0.0014) impaired with a significant (p = 0.0001) increase in the concentration of malondialdehyde (MDA) in the PFC and cerebellar tissue. In addition, the activities of glutathione increased (p = 0.0001) significantly in the CBZ + GSME-treated rats. All these anomalies were attenuated in the CBZ + GSME treated rats. Coadministration of GSME with CBZ may ameliorate CBZ-induced neurotoxicity, histoarchitectural disorganization of PFC and cerebellum with resultant effect on fine motor actions.

Graded doses of grape seed methanol extract attenuated hepato-toxicity following chronic carbamazepine treatment in male Wistar rats.

AIM: This study investigated the effects of co-administration of carbamazepine (CBZ) with grape (Vitis vinifera) seed methanolic extract (GSME) on liver toxicity. METHOD: Thirty-five male rats (145-155 g) were randomized into 5 groups (n = 7) and administered with propylene glycol (PG 0.1 mL/day), CBZ (25 mg/kg), CBZ (25 mg/kg) + GSME (200 mg/kg), CBZ (25 mg/kg) + GSME (100 mg/kg), or CBZ (25 mg/kg) + GSME (50 mg/kg) orally for 28 days. Twenty-four hours after the last dose, changes in the body weights were determined. The rats were euthanized by cervical dislocation. The liver was weighed and later homogenized; while the supernatant was analyzed biochemically. The liver tissues were preserved in 10 % neutral-buffered formalin for the histomorphological investigation. RESULT: There was significant (p = 0.0001) decrease in the body weight following carbamazepine treatment. The relative liver weight also decreased significantly (p = 0.0004) across the treatment group compared with control. The activities of the liver enzymes (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and glutathione activities), including the concentrations of malondialdehyde, increased significantly (p ≤ 0.0004) following carbamazepine treatment. Various morphological alterations were observed, especially in the photomicrograph of the CBZ treated rats. However, these derangements were attenuated significantly in the CBZ - GSME co-treated group. CONCLUSION: This study concludes that GSME treatment may serve as a potential therapeutic agent in carbamazepine-induced hepatotoxicity/ dysfunction.

Biochemical, hematological and histopathological evaluation of the toxicity potential of the leaf extract of Stachytarpheta cayennensis in rats.

BACKGROUND AND AIM: The many pharmacological potentials of Stachytarpheta cayennensis (L.C. Rich) Vahl, especially in managing central nervous system disorders, hypertension, diabetes and infections, have made it a subject of abuse, necessitating the need to ascertain its safety. This study therefore investigated the toxic effects of the leaf extract of S. cayennensis in rats following acute and 28-day repeated doses in male and female rats. EXPERIMENTAL PROCEDURE: Acute and repeated dose studies were conducted in male and female groups of rats (135-150 g), using OECD 423 and 407 Tests guidelines respectively. Functional observational battery, and body weights were monitored. Blood samples were analysed for haematological and plasma biochemical indices. Organs (brain, kidneys and liver) specimen were collected and weighed. Kidney and liver specimen were subjected to histopathological analysis. RESULTS AND CONCLUSION: The LD50 of the extract was greater than 5000 mg/kg, p.o. (24 h) suggesting that the extract may be non-toxic. However, following single and repeated doses, the results revealed varying degree of significant (p < 0.05) changes in biochemical and heamatological indices, as well as in relative body weight and organ-body and organ-brain weight ratios. Also, histological assessment revealed evidence of liver and kidney toxicities and recovery was incomplete, as signs of toxicities were still evident after 21 days of recovery. Therefore, the extract is potentially harmful to vital organs with evidence of sex differential adverse effects and non-reversible forms of toxicity, especially with repeated usage, necessitating the need to avoid indiscriminate use.

Therapeutic Potentials and Cytochrome P450-Mediated Interactions Involving Herbal Products Indicated for Diabetes Mellitus.

BACKGROUND: There has been an increase in the use of herbal products to complement conventional drugs in the treatment of various diseases especially in developing countries. This may be attributable to the potential cost-effectiveness and ease of accessibility of these products as well as the perception of their safety profiles. However, there are numerous literature reports on herbs altering the pharmacokinetics and pharmacodynamics of other co-administered drugs thereby modulating the therapeutic outcomes. The prevalence of diabetes is on a steady increase worldwide and it is now identified as one of the main threats to human health. OBJECTIVE: It is important that knowledge on specific effects of antidiabetic herbs and their products on drug metabolizing enzymes are updated and documented so as to ensure optimization of their therapeutic utility. This review, therefore, aims to highlight herbal products with evidence-based antidiabetic effects, identify their bioactive phyto-constituents, and also focus on the important Cytochrome P450 and consequences of their inhibition or induction. METHODS: An extensive literature search was undertaken and the information obtained were critically analyzed and discussed. RESULTS AND CONCLUSION: The literature abounds with reports on the utilization of herbal medications for the treatment of diabetes mellitus since time immemorial, but very few of these herbal products have undergone clinical trials. Also, studies on the herb-drug interactions were limited. Due to the complex phytochemical composition of the herbs, concomitant administration with conventional drugs resulted in alterations of pharmacological effects of some drugs. Evidences of beneficial interactions were identified for medical exploitation.

Sedative and anxiolytic effects of the extracts of the leaves of Stachytarpheta cayennensis in mice.

The leaves are used ethnomedicinally in Nigeria and other parts of the world for insomnia and anxiety among other uses. The investigations sought scientific evidence for the ethnomedicinal use of the leaves for the management of insomnia and anxiety as well as the neural mechanisms for the activities. The sedative and anxiolytic effects of the extracts of the leaves of Stachytarpheta cayennensis were examined in this study. The methanolic extract (5-50 mg/kg, i.p.) as well as the ethylacetate (10-50 mg/kg, i.p.), butanol and aqueous fractions (5-50 mg/kg, i.p.) of the extract were examined. Sedation was assessed as reduced novelty-induced rearing (NIR), reduced spontaneous locomotor activity (SLA) and increased pentobarbitone-induced sleeping time (PIST) in mice. The anti-anxiety effect (methanol 2.5-5.0; butanol 5.0; aqueous 20.0; ethylacetate 25.0 mg/kg, i.p.) was assessed using an elevated plus maze. LD50 was calculated for the extract and the fractions after the intraperitoneal route of administration using the Locke method. The methanolic extract, the butanol and the aqueous fractions inhibited rearing and spontaneous locomotion but prolonged pentobarbitone induced sleep. The ethylacetate fraction however increased both rearing and locomotion and decreased pentobarbitone sleeping time. The butanol and aqueous fractions, but not the methanol extract showed indices of open arm avoidance consistent with anti-anxiety effect. Naltrexone (2.5 mg/kg, i.p.) reversed the inhibition of rearing, locomotion and prolongation of pentobarbitone sleep due to the aqueous fraction of the extract. Flumazenil (2mg/kg, i.p.) abolished the effects of both methanolic extract and the butanol fraction on rearing, locomotion, pentobarbitone sleep and anxiety model. The methanolic extract, the butanol and aqueous fractions possess sedative activity while the ethylacetate fraction possesses stimulant property. The anxiolytic effect was found in both the aqueous fraction and the butanol fraction but not in the main methanol extract and also not in the ethylacetate fraction. Flumazenil, blocked the effect of the leaves of Stachytarpheta cayennensis on rearing, locomotion and elevated plus maze suggesting that GABA receptors are involved in the observed sedative and anxiolytic activities. This study also found opioid receptors involved in the sedative activity of the leaves of Stachytarpheta cayennensis. The rationale for the ethnomedicinal use of the leaves for the management of insomnia and anxiety were confirmed scientifically in this study.

Bronchorelaxant property of 'African potato' (Hypoxis hemerocallidea corm) aqueous extract in vitro.

This study was undertaken to investigate the bronchorelaxant effect of Hypoxis hemerocallidea corm ('African potato') aqueous extract (APE) on spasmogen-provoked contractions of guinea-pig isolated tracheal smooth muscle preparations. APE (25-400 mg/ml) relaxed spasmogen (histamine-, carbachol- and potassium-)-induced contractions of the isolated tracheal muscle preparations in a concentration-dependent manner. The relaxant effects of APE on spasmogen-evoked contractions of the tracheal muscle preparations were not altered by bath-applied propranolol (0.1-5.0 microg/ml), which markedly inhibited or completely abolished the relaxant effects of isoprenaline (0.1-5.0 microg/ml). Although the precise mechanism of the bronchorelaxant effect of APE could not be established in the present study, it is unlikely that the herb's aqueous extract stimulates the beta(2)-adrenoceptors present on the bronchial smooth muscles to produce its bronchodilatation. The finding that APE significantly relaxed (P<0.05) histamine-, carbachol- and high potassium ion concentration (K(+), 80 mM)-induced contractions of guinea-pig isolated bronchial muscle preparations appears to suggest that the bronchospasmolytic effect of the plant's extract is probably not mediated through a specific receptor, but rather, probably mediated via a non-specific bronchospasmolytic mechanism.

Hypoglycaemic and hypotensive effects of Momordica charantia Linn (Cucurbitaceae) whole-plant aqueous extract in rats.

Various morphological parts (roots, stems, leaves and fruits) of Momordica charantia Linn (family: Cucurbitaceae) are used traditionally in African folk medicine to manage, control and/or treat a plethora of human ailments, including diabetes mellitus and hypertension. In order to scientifically appraise some of the folkloric, anecdotal and ethnomedical uses of M charantia, the present study was undertaken to investigate the hypoglycaemic and hypotensive effects of M charantia whole-plant aqueous extract (MCE) in rat experimental paradigms. The hypoglycaemic effect of the plant extract was examined in normal and diabetic rats, using streptozotocin (STZ)- induced diabetes mellitus models. Normotensive (normal), and hypertensive Dahl salt-sensitive rats were used to probe the hypotensive (antihypertensive) effect of the plant extract. Chlorpropamide was used as reference hypoglycaemic agent for comparison. Acute oral administrations of the plant extract caused dose-related, significant hypoglycaemia in normal (normoglycaemic) and STZ-treated, diabetic rats. Furthermore, acute intravenous administrations of MCE produced dose-dependent, significant reductions in systemic arterial blood pressure and heart rates of normal, and hypertensive Dahl salt-sensitive rats. Although the exact hypoglycaemic and hypotensive mechanisms of action of the plant extract remain speculative at the moment, it is unlikely that the herb causes hypotension in the mammalian experimental animal model used via cholinergic mechanisms, since its cardiovascular effects are resistant to atropine pretreatment. However, the findings of this experimental animal study indicate that the plant extract possesses hypoglycaemic and hypotensive properties, and therefore, lend pharmacological credence to folkloric, ethnomedical uses of the plant in the management and/or control of diabetes mellitus and hypertension in some rural African communities.