Nuhu M. Danjuma

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.

Psychopharmacological properties of saponins from Randia nilotica stem bark

Abstract Context: Decoctions of Randia nilotica Stapf. (Rubiaceae) have been used in the Nigerian traditional medicine for the management of epilepsy, anxiety, depression and psychosis for many years and their efficacies are widely acclaimed among the rural communities of Northern Nigeria. Objective: The aim of this study is to establish whether the saponins present in R. nilotica are responsible for its acclaimed beneficial effects in Nigerian traditional medicine. Materials and methods: The behavioural properties of the saponin-rich fraction (SFRN) of R. nilotica stem bark were studied on hole-board, diazepam-induced sleep, rota-rod and beam-walking in mice. The anticonvulsant properties of SFRN were also examined on maximal electroshock, pentylenetetrazole- and strychnine-induced seizures in mice. Results: The intraperitoneal LD50 of SFRN in mice and rats were estimated to be 11.1 and 70.7 mg/kg, respectively. SFRN significantly prolonged the duration of diazepam-induced sleep; diminished head dip counts in the hole-board test and protected mice against maximal electroshock seizures. SFRN failed to protect mice against pentylenetetrazole- and strychnine-induced seizures; and had no effect on motor coordination on the rota-rod treadmill at the doses tested. SFRN significantly decreased the number of foot slips in the beam-walking assay in mice with no effect on time to reach the goal box. Discussion and conclusion: This study provides evidence of the psychopharmacological effects of SFRN, thus supporting further development of the psychoactive components as remedies for epilepsy.

Anticonvulsant properties of methanol leaf extract of Laggera Aurita Linn. F. (Asteraceae) in laboratory animals.

ETHNOPHARMACOLOGICAL RELEVANCE Preparation of Laggera aurita Linn. (Asteraceae) is widely used in traditional medicine to treat various kinds of diseases such as epilepsy, malaria, fever, pain and asthma. Its efficacy is widely acclaimed among communities in Northern Nigeria. AIM OF THE STUDY The present study is aimed at establishing the possible anticonvulsant effects of the methanol leaf extract of Laggera aurita using acute and chronic anticonvulsant models. MATERIALS AND METHOD Median lethal dose (LD50) was determined in mice and rats via oral and intraperitoneal routes. Anticonvulsant screening of the extract was performed using maximal electroshock-induced seizure test in day-old chicks; pentylenetetrazole-, strychnine- and picrotoxin- induced seizure models in mice. Similarly; its effects on pentylenetetrazole-induce kindling in rats as well as when co-administered with fluphenamic and cyproheptadine in mice, were evaluated. RESULTS Median lethal dose (LD50) values were found to be >5000mg/kg, p.o. and 2154mg/kg, i.p., each for both rats and mice. The extract showed dose dependent protection against tonic hind limb extension (THLE) and significantly (p<0.05) decreased the mean recovery from seizure in the maximal electroshock-induced seizure. In the pentylenetetrazole-induced seizure model, the extract offered 50% protection at 600mg/kg and also increased the mean onset of seizure at all doses with significant (p<0.05) increase at the highest dose (600mg/kg). Similarly the extract produced significant (p<0.05) increase in the onset of seizures in both strychnine- and picrotoxin- induced seizure models, at all the doses except at 150mg/kg for the picrotoxin model. Co-administration of fluphenamic acid (FFA) (5mg/kg) and the extract (600mg/kg) showed an enhanced effect with percentage protection of 70% while co-administration of FFA (5mg/kg) and phenytoin (5mg/kg) as well phenytoin (5mg/kg) and the extract (600mg/kg) produced an additive effect. Administration of the extract (600mg/kg), phenytoin (20mg/kg) and cyproheptadine (4mg/kg) offered 40%, 100% and 0% protection against THLE, each respectively, while co-administration of cyproheptadine (4mg/kg) and the extract (600mg/kg) as well as co-administration of cyproheptadine (4mg/kg) and phenytoin (20mg/kg) offered reduced protection of 20% and 50% each respectively. The extract at all doses reduced the severity of seizure episodes induced by PTZ-induced kindling. CONCLUSION The results suggest that the methanol leaf extract of Laggera aurita possesses anticonvulsant and antiepileptogenic properties.

Elucidation of the possible mechanism of analgesic actions of butanol leaf fraction of Olax subscorpioidea Oliv

ETHNOPHARMACOLOGICAL RELEVANCE Preparations of Olax subscorpioidea have been used traditionally for the management of pains, inflammatory diseases, yellow fever, cancer and rheumatism. Previously, the analgesic activity of its leaf extract have been reported. Furthermore, an analgesic assay guided fractionation showed that the butanol soluble fraction is the most active. However, the mechanism of this activity remains to be elucidated. This present study investigated the possible pharmacological mechanisms involved in the analgesic activity of the butanol leaf fraction of Olax subscorpioidea (BFOS) using the acetic acid induced writhing test in mice. MATERIALS AND METHODS Animals were orally administered distilled water (10ml/kg), BFOS (1,000mg/kg) and morphine (10mg/kg) 60minutes before i.p administration of acetic acid and the resulting writhing were counted for 10minutes. To establish the possible mechanism(s) of action of BFOS, separate group of animals were pretreated with naloxone (2mg/kg, i.p), prazosin (1mg/kg, i.p), yohimbine (1mg/kg, i.p), propranolol (20mg/kg, i.p), metergoline (2mg/kg, i.p), glibenclamide (5mg/kg, i.p) and l-arginine (50mg/kg, i.p) 15minutes before BFOS. RESULTS BFOS and morphine showed marked analgesic activities (p<0.001); the pretreatment of animals with naloxone, metergoline and l-arginine significantly (p<0.05 and p<0.001) reduced the analgesic activity of BFOS; however, pretreatment with prazosin, yohimbine, propranolol and glinbenclamide showed no effect on its analgesic activity. CONCLUSION Results obtained in this study suggest the involvement of opioidergic, serotonergic and nitric oxide-l-arginine pathways in the analgesic effect of butanol leaf fraction of Olax subscorpioidea.

Chronic administration of ethanol leaf extract of Moringa oleifera Lam. (Moringaceae) may compromise glycaemic efficacy of Sitagliptin with no significant effect in retinopathy in a diabetic rat model

ETHNOPHARMACOLOGICAL RELEVANCE Moringa oleifera Lam. (Moringaceae) has gained awareness for its antidiabetic effect, and is used as alternative therapy or concurrently with orthodox medicines such as sitagliptin in diabetes mellitus. This is without ascertaining the possibility of drug-herb interactions, which could either lead to enhanced antidiabetic efficacy, increased toxicity, or compromised glycaemic control with negative consequence in diabetic retinopathy. AIM OF THE STUDY To investigate the effect, of sitagliptin (50mg/kg), Moringa oleifera (300mg/kg) leaf extract, and a combination of both on glycaemic control parameters, lenticular opacity and changes in retinal microvasculature in alloxan (150mg/kg i.p) induced diabetic rat model. MATERIALS AND METHOD Seven groups of eight rats per group were used, with groups I, II and VII as normal (NC), diabetic (DC) and post-prandial controls (PPC). Groups III to VI were diabetic rats on sitagliptin (III), M. oleifera (IV), sitagliptin and M. oleifera (SM) (V), for 42 days with 2 weeks delayed treatment in a post-prandial hyperglycaemic group (PPSM) (VI). Glycaemic control parameters, insulin levels, body weights, and effects of retinal microvasculature on lenticular opacity/morphology were investigated. RESULTS A significant decrease in fasting blood glucose (FBG) levels was displayed in SM group from day 14(60%) (p<0.01) to day 28 (38%) (p<0.01) of treatment, compared to day 1. Thereafter, a steady increase of up to 57% on day 42 compared to day 28 was observed. A significant decrease in random blood glucose (RBG) levels, were demonstrated on day 42 (24%) (p<0.001), compared to day 1. No significant difference was seen in mean serum levels of insulin across groups. No significant changes in body weights. Evidence of mild lenticular opacity was observed, with no significant effect in pathologic lesions in the retina. CONCLUSION The chronic co-administration of sitagliptin and M. oleifera showed a progressive decrease in anti-hyperglycaemic effect of sitagliptin, and although it delayed the onset of lenticular opacity (i.e. cataract-like changes) it did not prevent the progression nor ameliorated pathologic lesions in the retina.

Sitagliptin–Moringa oleifera coadministration did not delay the progression nor ameliorated functional and morphological anomalies in alloxan-induced diabetic nephropathy

OBJECTIVE: Sitagliptin (ST) and Moringa oleifera (MO) Lam (Moringaceae) are used concomitantly by diabetic patients, with no study ascertaining for potential favorable or otherwise renal implications. We investigated the effect of coadministration of ST and MO leaf extract on functional and morphological biomarkers of alloxan-induced diabetic nephropathy (DN). MATERIALS AND METHODS: Diabetes was induced with a single dose of 150 mg/kg of alloxan intraperitoneally. Seven groups of eight rats per group were used, with Groups I, II, and VII as normal (NS), diabetic control (DC), and postprandial controls. Groups III, IV, V, and VI were diabetic rats on ST, MO, ST and MO (SM), for 42 days with 2 weeks delayed treatment in a postprandial hyperglycemic group (PPSM), respectively. Serum urea, albumin, electrolyte levels, lipid profile, and kidney tropism were determined in addition to histological examinations. RESULTS: There was a significant increase (P < 0.05) in kidney tropism comparing all drug-treated groups and DC to normal rats. Significant increases in serum urea were observed (P = 0.02) in DC, MO-treated, and SM-treated rats compared to normal rats and also in serum triglyceride (P < 0.05) in MO-treated and SM-treated rats compared to controls and other drug-treated groups. A mild reduction in severity of pathologic lesions was observed (glomerulosclerosis Grade 1) in SM-treated rats compared to a marked necrosis in DC (Grade 3). CONCLUSION: The coadministration of ST–MO did not delay the progression of functional anomalies and renal injury nor ameliorated the lesions associated with chronic DN in Wistar rats.