Esther O. Agbaje

Anti-obesity and antihyperlipidaemic effect of Hunteria umbellata seed extract in experimental hyperlipidaemia

AIM OF THE STUDY In Nigerian folk medicine, water infusion of the dried seeds of Hunteria umbellata (K. Schum.) Hallier f. has a reputation for the local management of obesity and hyperlipidaemia. The present study is aimed at evaluating the anti-obesity and antihyperlipidaemic activities as well as the underlying mechanisms of action of the aqueous seed extract of Hunteria umbellata (HU) in normal, triton-induced, and olive oil-induced hyperlipidaemic rats. MATERIALS AND METHODS Normal and olive oil-induced hyperlipidaemic, and triton-induced hyperlipidaemic rats were pre-treated with single, daily oral administration of 10 ml/kg of distilled water, 20 mg/kg of simvastatin, 50 mg/kg, 100 mg/kg and 200 mg/kg of HU in 10 ml/kg of distilled water for 28 days and 24 h. The effects of these drugs on % body weight change, feeding pattern, serum lipids, coronary artery risk index (CRI) and atherogenic index (AI) and Lees index (LI) were investigated. RESULTS Oral pre-treatment with simvastatin and graded oral doses of HU significantly (p<0.05) reduced the weight gain pattern and caused dose related (p<0.05, p<0.01 and p<0.001) reductions in the serum lipids, CRI, AI and LI. Also, HU pre-treatment significantly improved triton-induced hepatic histological lesions. CONCLUSIONS Results of this study showed that HU has both anti-obesity and antihyperlipidaemic effects which may partly be mediated via inhibition of intestinal lipid absorption and de novo biosynthesis of cholesterol. Thus, the results justify the ethnopharmacological use of the extract in the management of obesity and hyperlipidaemia.

Analgesic and anti-inflammatory effects of the methanol root extracts of some selected Nigerian medicinal plants

Abstract Context: The roots of Alafia barteri Oliver (Apocynaceae), Combretum mucronatum Schumach (Combretaceae) and Capparis thonningii Schum (Capparaceae) are used in Traditional African Medicine to alleviate painful and inflammatory conditions. Objective: This study investigated the analgesic and anti-inflammatory effects of the methanol root extracts of Alafia barteri (MeAB), C. mucronatum (MeCM), and Capparis thonningii (MeCT). Materials and methods: Analgesic activity of the extracts (50, 100, and 200 mg/kg, p.o. 1 h) was evaluated using acetic acid-, formalin- and hot plate-induced pain while anti-inflammatory actions (100 or 200 mg/kg) were investigated using the carrageenan- and xylene-induced edema tests. Results: MeAB, MeCM, and MeCT (200 mg/kg) inhibited acetic acid-induced abdominal constriction by 55.07, 46.67, and 47.25%, respectively. In the formalin test, the index of pain inhibition of early and late phases was, respectively, 47.83 and 81.98% for MeAB, 56.10 and 63.81% for MeCM, and 42.84 and 63.29% for MeCT (200 mg/kg). MeAB and MeCT pretreatments significantly increased the reaction time by 46.67 and 25.53%, respectively, 120 min post-treatment in the hot-plate test. Naloxone (5 mg/kg, s.c.) pretreatment 15 min before extract administration, significantly (p < 0.05) reversed the analgesic effect of MeAB and MeCT in the formalin test. MeAB, MeCM, and MeCT showed significant anti-inflammatory activity with 60.44 and 30.39%, 63.74 and 58.08%, and 50.55 and 77.84% (200 mg/kg, 4 h), respectively, inhibition of paw and ear edema. Discussion and conclusion: The analgesic and anti-inflammatory effects of MeAB and MeCT involve an interaction with opioid pathway and/or inhibition of chemical mediators of pain and inflammation.

Protective effect of Cnestis ferruginea and its active constituent on scopolamine-induced memory impairment in mice: A behavioral and biochemical study

Abstract Context: Cnestis ferruginea Vahl ex DC (Connaraceae) (CF) is used in traditional African medicine in the management of CNS disorders. The degeneration and dysfunction of cholinergic neurons is closely associated with the cognitive deficits of Alzheimer’s disease (AD) and oxidative stress has been implicated in its pathogenesis. However, the influence of C. ferruginea on the cholinergic system and oxidative stress parameters has not been explored. Objective: The present study investigates the effect of methanol root extract of C. ferruginea and its active constituent amentoflavone (CF-2) on memory, oxidative stress and acetylcholinesterase (AChE) activity in scopolamine-induced amnesia. Materials and methods: Mice were orally treated with CF (25–200 mg/kg), CF-2 (6.25–25 mg/kg) for three days and memory impairment was induced by intraperitoneal injection of scopolamine (3 mg/kg). Memory function was evaluated by passive avoidance and Morris water maze tests. Biochemical parameters of oxidative stress and cholinergic function were estimated in brain after the completion of behavioral studies. Results: Scopolamine caused memory impairment along with increased AChE activity and oxidative stress in mice brain. Oral administration of CF and CF-2 significantly prevented scopolamine-induced memory impairment, inhibited AChE and enhanced antioxidant enzyme activity in the brain following scopolamine injection as compared to vehicle administration in scopolamine (i.p.)-treated mice that were comparable to the effect of tacrine. Discussion and conclusion: The study demonstrated that C. ferruginea and its constituent have significant protective effect against scopolamine-induced memory deficits in mice that can be attributed to their antioxidant and antiAChE activity.

EFFECT OF SUBCLINICAL, CLINICAL AND SUPRACLINICAL DOSES OF CALCIUM CHANNEL BLOCKERS ON MODELS OF DRUG-INDUCED HEPATOTOXICITY IN RATS

Drug-related hepatotoxicity is the leading cause of acute liver failure, and hepatic problems are responsible for a significant number of liver transplantations and deaths worldwide. Calcium has been associated with various metabolic processes that lead to cell death and apoptosis, and increased cytosolic Ca2+ has been implicated in hepatotoxicity. This study was designed to investigate the effects of calcium channel blockers (CCBs) on isoniazid-rifampicin, zidovudine and erythromycin-induced hepatotoxicity in rats. Treatment groups comprised control, hepatotoxicant, hepatotoxicant along with each of silymarin, nifedipine, verapamil and diltiazem at subclinical, clinical and supraclinical doses. A day to the end of treatment for each model, rats were subjected to the hexobarbitone-induced hypnosis test. On the last days of treatment, blood samples were collected and serum was analyzed for relevant biochemical parameters. Animals were sacrificed after blood collection and livers were harvested, and samples obtained for in vivo antioxidant indices assay and histopathology. The hepatotoxicants significantly increased serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP), as well as duration of sleep in the hypnosis test. These drugs significantly reduced the hepatic levels of reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and increased the level of malondialdehyde (MDA). The CCBs at the various doses significantly reversed the effects of isoniazid-rifampicin, zidovudine and erythromycin. The results obtained in this study suggest that the CCBs possess hepatoprotective activity in drug-induced hepatotoxicity and may be beneficial at the subclinical and clinical doses.

Combretum mucronatum and Capparis thonningii prevent scopolamine-induced memory deficit in mice

Context: Roots of Combretum mucronatum Schumach. & Thonn. (Combretaceae) and Capparis thonningii Schum. (Capparaceae) are used in southwest Nigeria in the treatment of inflammatory disorders and mental illness. Objective: This study evaluated the antidementic effect of the methanol root extracts of C. mucronatum and C. thonningii on scopolamine (3 mg/kg, i.p.) induced memory impairment in mice. Materials and methods: The effect of C. mucronatum and C. thonningii (50–200 mg/kg) administered orally for 3 days on memory impairments induced in mice by scopolamine was assessed in the passive avoidance and Morris water maze test and compared with that of tacrine (5 mg/kg, i.p.). The activities of acetylcholinesterase (AchE) and antioxidant enzymes were estimated in the brain after the completion of behavioral studies. Results: C. mucronatum and C. thonningii root extracts (50–200 mg/kg) reversed scopolamine-induced memory deficit with significant (p < 0.05) increase in transfer latency in passive avoidance test. Similarly, the extracts (200 mg/kg) ameliorated memory deficit as a result of significant (p < 0.001) decrease in escape latency and path length in Morris water maze test. The increased AChE activity induced by scopolamine was significantly (p < 0.05) inhibited by C. mucronatum and C. thonningii (100 and 200 mg/kg) treatment which was similar to the effect of tacrine. Both extracts significantly (p < 0.05) attenuated scopolamine-induced increase in oxidative stress parameters as well as restoration of glutathione activity. Discussion and conclusion: C. mucronatum and C. thonningii extracts possess significant anticholinesterase, antioxidant and antidementic properties, which may be useful in the management of Alzheimer’s disease.

Antidepressant-like effect of the hydroethanolic leaf extract of Alchornea cordifolia (Schumach. & Thonn.) Mull. Arg. (Euphorbiaceae) in mice: Involvement of monoaminergic system

ETHNOPHARMACOLOGICAL RELEVANCE The leaf of Alchornea cordifolia (Euphorbiaceae) is used in traditional African medicine in the treatment of various neurological and psychiatric disorders including depression. Previous studies have shown its potent antidepressant-like effect in the forced swimming test (FST). Hence, this study sought to investigate the involvement of monoaminergic systems in the antidepressant-like effect elicited by hydroethanolic leaf extract of Alchornea cordifolia (HeAC) in the FST. MATERIALS AND METHODS HeAC (25-400mg/kg, p.o.) was administered 1h before the FST. To investigate the contribution of monoaminergic systems to antidepressant-like effect, receptors antagonists were injected 15min before oral administration of HeAC (200mg/kg) to mice and 1h thereafter, subjected to FST. RESULTS HeAC (200 and 400mg/kg, p.o.) produced dose dependent and significant (P<0.001) antidepressant-like effect, in the FST, without accompanying changes in spontaneous locomotor activities in the open-field test. The anti-immobility effect of HeAC (200mg/kg) in the FST was prevented by pretreatment of mice with SCH 23390 (0.05mg/kg, s.c., a dopamine D1 receptor antagonist), sulpiride (50mg/kg, i.p., a dopamine D2 receptor antagonist), prazosin (1mg/kg, i.p., an α1-adrenoceptor antagonist), yohimbine (1mg/kg, i.p., an α2-adrenoceptor antagonist), and GR 127993 (5-HT1B receptor antagonist). Similarly, 3 days intraperitoneal injection of p-chlorophenylalanine (pCPA, 150mg/kg, i.p., an inhibitor of serotonin synthesis) prevented the antidepressant-like effect elicited by HeAC. The combination of subeffective doses of imipramine (5mg/kg, p.o.) or fluoxetine (5mg/kg, p.o.), with HeAC (25mg/kg, p.o., subeffective dose) produced a synergistic antidepressant-like effect in the FST. CONCLUSION The hydroethanolic extract of Alchornea cordifolia possesses antidepressant-like effect mediated through interaction with dopamine (D1 and D2), noradrenergic (α1 and α2 adrenoceptors), and serotonergic (5HT1B receptors) systems. Also, the potentiation of the anti-immobility effect of conventional antidepressants (fluoxetine and imipramine) by Alchornea cordifolia suggest potential therapeutic effect in depression.

Antidepressant, anxiolytic, and anticataleptic effects of aqueous leaf extract of Antiaris toxicaria Lesch. (Moraceae) in mice: possible mechanisms of actions

Abstract Background: The leaves of Antiaris toxicaria Lesch. (Moraceae) are used by traditional medicine practitioners in southwest Nigeria in the management of epilepsy, wounds, and neurological disorders. Hence, this study was undertaken to investigate the effect of the aqueous leaf extract of A. toxicaria on the central nervous system. Methods: One hour after administration of A. toxicaria [50–300 mg/kg orally (p.o.)], its antidepressant effect was evaluated using the forced swimming test (FST), anxiolytic effect using elevated plus maze (EPM) test, and anticataleptic effect using haloperidol-induced catalepsy, whereas its effects on hypnosis and motor coordination were studied using hexobarbitone-induced sleeping time and open-field tests, respectively, in mice. Results: Antiaris toxicaria (300 mg/kg) significantly increased swimming activity (36.88%) and reduced immobility time (38.54%). Pretreatment of mice with prazosin (an α1-adrenoceptor antagonist), sulpiride (a D2 receptor antagonist), and l-NG-nitro-arginine (nitric oxide synthase inhibitor) 15 min before A. toxicaria (300 mg/kg p.o.) treatment significantly prevented its antidepressant-like effect by 35.58%, 53.30%, and 56.11%, respectively, in the FST. However, pretreatment with metergoline (5-HT2 receptor antagonist), and atropine (muscarinic cholinergic antagonist) failed to reverse this effect. Interestingly, A. toxicaria (50 mg/kg) significantly increased open-arm exploration in the EPM by 70.31%, which was reversed by 82.66% in the presence of flumazenil [3 mg/kg intraperitoneally (i.p.)]. Haloperidol (1 mg/kg i.p.) induced cataleptic behavior in mice, which was reversed by A. toxicaria (300 mg/kg) (p<0.001) treatment. Conclusions: The results suggest that A. toxicaria possesses an antidepressant-like effect involving interaction with α1-adrenoceptor, D2 dopamine receptor, and nitrergic pathway; an anxiolytic-like effect linked to the benzodiazepine system; and a neuroprotective effect.

Assessing the Risk of Birth Defects Associated with Exposure to Fixed-Dose Combined Antituberculous Agents during Pregnancy in Rats

Due to the risks of disease progression and transmission to the newborn, treatment of tuberculosis is often pursued during pregnancy and fixed-dose combined antituberculous agents have been found to be beneficial. Unfortunately, there is paucity of data on the safety of the fixed-dose combined antituberculous drugs during pregnancy. This study intends to assess the teratogenic effect of fixed-dose combined antituberculous drugs on the organogenesis stage of fetal development and also investigate the possible roles of vitamin C in modulating the teratogenic effects of these agents on the fetus using animal model. Pregnant rats were divided into 3 groups with 12 animals per group: group 1 received distilled water (10 mL/kg) orally; group 2 received 51.4 mg/kg/day of fixed-dose combined antituberculous agents orally; group 3 received 51.4 mg/kg/day of fixed-dose combined antituberculous agents plus vitamin C (10 mg/kg/day) orally. Six rats in each group were randomly selected and sacrificed on day 20 by cervical dislocation prior to day 21 of gestation, and the foetuses were harvested through abdominal incision for physical examination. Blood samples were collected from the 1st filial rats of the remaining six animals for biochemical and hematological examination. The liver, kidney, heart, and brain of all the sacrificed animals were used for histopathological examination. There were significant (P ≤ 0.05) low birth weights of the foetuses of the animals that were treated with fixed-dose combined antituberculous agents. The haematological parameters also revealed a reduction in the platelets counts and neutrophiles at the first filial generation. Significant (P ≤ 0.05) elevations in the levels of aspartate aminotransferase (AST) and alkaline phosphatase (ALP) in the foetuses of the animals treated with fixed-dose combined antituberculous agents were also observed. However, the combination of vitamin C with fixed-dose combined antituberculous agents significantly (P ≤ 0.05) reduced the level of AST. Fixed-dose combined antituberculous agents have teratogenic potential as shown in low birth weight and mild liver damage in the first filial of the treated animals. As much as it is imminent to treat TB patients in pregnancy, there is need to always exercise caution and clinically weigh the risk-benefit ratio.

Biochemical, hematological, and hormonal profile of rats orally administered methanol stem bark extract of Napoleona vogelii Hook and Planch (Lecythidaceae)

Abstract Napoleona vogelii is used in traditional medicine for the management of stomach aches, ulcer, and cancers. This study was conducted to investigate the subchronic toxicological effect of methanol stem bark extract of N. vogelii on biochemical, hematological, and hormonal profile of male and female rats. Forty rats of both sexes were randomly divided into four groups of 10 rats each and were administered 100, 200, and 400 mg/kg of the extract p.o. for 90 d. Ten milliliter per kilogram of distilled water p.o. was administered to control rats. On hematological assessment, mean corpuscular hemoglobin concentration was significantly (p < 0.01) increased at 400 mg/kg compared to control. Biochemical assessment showed a significant increase (p < 0.05) in levels of alanine aminotransferase and aspartate aminotransferase at 200 and 400 mg/kg, respectively, compared to control. Hormonal assessment of male rats revealed a significantly (p < 0.0001) reduced level of testosterone at all treatment doses compared to control while estradiol was significantly (p < 0.05) reduced at 100 mg/kg, but significantly (p < 0.0001) increased at 200 and 400 mg/kg respectively compared to control in female rats. Findings from this study demonstrate that N. vogelli is relatively safe on oral acute exposure but may possess the potential to cause hepatic dysfunction and infertility in male rats by perturbations of the hypothalamic-pituitary axis while conversely enhancing fertility in female rats on subchronic administration.

Antigenotoxic and Antioxidant Activity of Methanol Stem Bark Extract of Napoleona Vogelii Hook & Planch (Lecythidaceae) In Cyclophosphamide-Induced Genotoxicity

BACKGROUND: Napoleona vogelii is used in traditional medicine for cancer management. AIM: The study was conducted to evaluate the antigenotoxic and antioxidant activities of methanol stem bark extract of N. vogelii in male Sprague Dawley rats. MATERIALS AND METHOD: Thirty male Sprague Dawley rats were randomly divided into group 1 (control) administered 10 mL/kg distilled water, groups 2 and 3 were co-administered 100 mg/kg, 200 mg/kg of N. vogelli and 5 mg/kg cyclophosphamide (CPA) respectively for 7 days p.o. Groups 4 and 5 were administered only 5 mg/kg CPA and 200 mg/kg NV respectively. RESULTS: The LD50 oral was greater than 4 g/kg. There were significant (p < 0.0001) increases in plasma enzymatic and non-enzymatic antioxidant enzymes and significant (p < 0.0001) decrease in percentage micronuclei in bone marrow of extract treated rats compared to rats administered 5 mg/kg CPA alone. There was steatosis pointing to cytotoxic injury in the liver of rats co-administered 200 mg/kg NV and 5 mg/kg CPA. Gas chromatography-mass spectrometry analysis of the extract showed the presence of phytol and unsaturated fatty acids. CONCLUSION: N. vogelii possesses antigenotoxic and antioxidant activities associated with the presence of phytochemicals, phytol and unsaturated fatty acids.