In vivo antiplasmodial activities and acute toxicity assessment of two plant cocktail extracts commonly used among Southwestern Nigerians.

Discovering and developing the desired antimalarials continue to be a necessity especially due to treatment failures, drug resistance, limited availability and affordability of antimalarial drugs and costs especially in poor malarial endemic countries. This study investigated the efficacies of two plant cocktails; CtA and CtB, selected based on their traditional usage. Efficacies of the cocktail extracts, chloroquine and pyrimethamine against Plasmodium berghei berghei were evaluated in mice using the suppressive, curative and prophylactic test models, after oral and intraperitoneal acute toxicity determination of the plant cocktails in accordance with Lorke's method. Data was analyzed using SPSS software version 23.0 with level of significance set at P < 0.05. The median lethal dose was determined to be higher than 5000 mg/kg body weight orally for both CtA and CtB; and 316.23 mg/kg body weight intraperitoneally for CtA. Each cocktail exhibited high dose dependent Plasmodium berghei berghei inhibition which was 96.95% and 99.13% in the CtA800 mg/kg and CtB800 mg/kg doses in the curative groups respectively, 96.46% and 78.62% for CtA800mg/kg and CtB800mg/kg doses in the suppressive groups respectively, as well as 65.05% and 88.80% for CtA800mg/kg and CtB800mg/kg doses in the prophylactic groups respectively. Throughout the observation periods, the standard drugs, chloroquine phosphate and pyrimethamine maintained higher inhibitions up to 100%. These findings demonstrate that CtA and CtB possess good antimalarial abilities and calls for their development and standardization as effective and readily available antimalarial options. The acute toxicity results obtained underscore the importance of obtaining information on toxicities of medicinal plant remedies before their administration in both humans and animals.

Evaluation of cardiotoxicity and other adverse effects associated with concomitant administration of artemether/lumefantrine and atazanavir/ritonavir-based antiretroviral regimen in patients living with HIV.

The interplay of artemether-lumefantrine (AL) and atazanavir-ritonavir (ATVr) with Cytochrome P (CYP) 3A4 isoenzyme and QTc-interval may spawn clinically significant drug interactions when administered concomitantly. Cardiotoxicity and other adverse effects associated with interaction between AL and ATVr were evaluated in patients with HIV infection and malaria comorbidity. In a two-arm parallel study design, six doses of AL 80/480 mg were administered to 20 participants [control-arm (n = 10) and ATVr-arm (n = 10)], having uncomplicated Falciparum malaria, at intervals of 0, 8, 24, 36, 48 and 60 h respectively. Participants in the control arm took only AL while those in ATVr-arm took both AL and ATVr-based ART regimen. Electrocardiography, adverse events monitoring and blood tests were carried out for each of them at pre and post doses of AL. Data obtained were analyzed. QTc-interval was significantly increased in the ATVr-arm (0.4079 ± 0.008 to 0.4215 ± 0.007 s, p = 0.008) but not in the control-arm (0.4016 ± 0.018 to 0.4024 ± 0.014 s, p = 0.962). All values were, however, within normal range [0.36 - 0.44 / 0.46 s (male/female)]. General body weakness and chest pain were new adverse events reported, at post-dose of AL, in the ATVr-arm but not in the control-arm. There was no significant change (p > 0.05) in the plasma levels of creatinine, alanine aminotransferase, aspartate aminotransferase and hemoglobin at post-dose compared to pre-dose of AL in both arms of study. Concomitant administration of artemether-lumefantrine with atazanavir-ritonavir-based regimen is potentially cardiotoxic but not associated with clinically significant renal, blood nor liver toxicities. They must be used with caution.

Anticonvulsant activity of Nymphaea lotus Linn. extract in mice: The role of GABAergic-glutamatergic neurotransmission and antioxidant defence mechanisms.

Epilepsy remains an unmet medical need affecting more than 50 million people worldwide with about 125,000 mortality annually and more prevalent in low- and middle-income countries. Nymphaea lotus (also known as water lilly) is an aquatic plant used traditionally to treat convulsive episodes in Southwestern Nigeria. This study was undertaken to evaluate anticonvulsant activity of aqueous Nymphaea lotus extract (ANL) and ethanol Nymphaea lotus extract (ENL) on chemical-induced seizures in mice as well as possible mechanisms of action. Vehicle (10 mL/kg, p.o.), ANL (50-200 mg/kg, p.o.), ENL (50-200 mg/kg) or diazepam (5 mg/kg, p.o.) was administered 1 h prior to chemo-convulsant (picrotoxin (PCT), pentylenetetrazol (PTZ), strychnine or N-methyl-D-aspartate (NMDA)) administration. Most effective doses of the extracts were administered to mice after the establishment of temporal lobe epilepsy (TLE) induced by kainic acid. Thereafter, memory assessment in Y-maze, depressive-like behaviour in tail suspension test (TST) and anxiety model in elevated plus maze test (EPM). The prefrontal cortex and hippocampus were assayed for oxidative stress parameters. The pretreatment of mice with ANL or ENL significantly prolonged onset of seizures and reduced the duration of picrotoxin-, pentylenetetrazol-, and strychnine-induced seizures or NMDA-induced turning behaviour. Kainic acid induced spontaneous recurrent seizures and oxidative stress were ameliorated by N. lotus extracts. Moreover, N. lotus-induced anticonvulsant action was reversed by the pretreatment of mice with flumazenil (benzodiazepine receptor antagonist) or L-arginine (nitric oxide precursor). In addition, kainic acid induced neurodegeneration was reduced by N. lotus extract. Findings from this study showed anticonvulsant activity of Nymphaea lotus in neurotoxins-induced seizures through enhancement of inhibitory GABAergic/ antioxidant signalling and inhibition of glutamatergic neurotransmission.

Sub-chronic toxicological evaluation of Strophanthus hispidus DC (Apocynaceae) aqueous root extract.

OBJECTIVES: Strophanthus hispidus DC (Apocynaceae) has gained wide and extensive applications in herbal medicine in Africa for the treatment of quite a lot of diseases. Owing to the extensive application and the propensity of persistent consumption of this shrub, this research investigates the sub-chronic toxicological effect of aqueous root extract of S. hispidus (SHP) in laboratory animals (rats). METHODS: The rats were allotted into four groups of eight rats each (n=8) and orally treated daily for ninety (90) days with SHP extract at 100, 500 and 1,000 mg/kg and the control group received distilled water (10 mL/kg). The rats were weighed at 15 days interval. After 90 days daily oral administration of SHP extract, blood samples were collected from the rats into lithium heparin and EDTA bottles for biochemical and haematological analysis respectively. Vital organs were weighed and histological examination was performed on the liver and kidney. RESULTS: The SHP extract displayed no significant (p>0.05) alterations in body weight of treated compared to control rats. At doses of 500 and 1,000 mg/kg, SHP-treated rats showed significant (p<0.05) increase in white blood cell (WBC), without significant difference in other haematological parameters. Non-significant (p>0.05) decrease in urea and non-significant (p>0.05) increase Na+, K+ and blood urea nitrogen (BUN) were observed. Significant (p<0.05) decrease in liver weight was observed without any alteration in the architecture of the liver and other organs investigated. CONCLUSIONS: Aqueous root extract of S. hispidus demonstrated a good safety profile in rats. Therefore, S. hispidus is harmless and safe following sub-chronic oral administration.

Evaluation of the effects of atazanavir-ritonavir on the pharmacokinetics of lumefantrine in patients living with HIV in Lagos University Teaching Hospital, South-Western Nigeria.

PURPOSE: Atazanavir-ritonavir (ATVr)-based antiretroviral therapy and artemether-lumefantrine (AL) are commonly used drugs for the treatment of human immune deficiency virus (HIV) infection and malaria respectively. However, interaction of both drugs, with Cytochrome P 3A4 (CYP 3A4) isoenzyme, may spawn clinically significant pharmacokinetic interactions. This study evaluated the effects of atazanavir-ritonavir on the pharmacokinetics of lumefantrine. METHOD: In a case-control study, twenty participants having Plasmodium falciparum malaria were recruited and divided into two groups (ATVr-arm, n=10; and control-arm, n= 10). All the participants were administered six oral doses of AL 80-480 mg (Coartem). Thereafter, their blood samples were collected at different time intervals over seven days. The concentration of lumefantrine in each sample was quantified with high-performance liquid chromatography (HPLC) and used to determine its pharmacokinetic parameters which were compared between the test and control groups. RESULTS: ATVr increased the mean day 7 concentration of lumefantrine (ATVr 3847.09 ± 893.35 ng/mL, control 1374.53 ± 265.55 ng/mL, p = 0.016) and the area under its plasma concentration-time curve (ATVr 670529.57 ± 157172.93 ng.h/mL, control 447976.28 ± 80886.99 ng.h/mL, p = 0.224) by 179.88 % and 49.68 %, respectively, but decreased its mean maximum plasma drug concentration (Cmax) (ATVr 13725.70 ± 2658.44 ng/mL, control 15380.48 ± 2332.62 ng/mL, p = 0.645) by 10.76 %. CONCLUSION: ATVr increased drug exposure and day 7 plasma concentration of lumefantrine. AL is therefore considered effective for the treatment of malaria in patients taking ATVr-based regimen. However, the safety associated with the interaction requires further elucidation. TRIAL REGISTRATION: Clin ClinicalTrials.gov Identifier: NCT04531072, August 27, 2020. "Retrospectively registered".

Effect of nevirapine, efavirenz and lopinavir/ritonavir on the therapeutic concentration and toxicity of lumefantrine in people living with HIV at Lagos University Teaching Hospital, Nigeria.

Patients living with HIV in malarial endemic regions may experience clinically significant drug interaction between antiretroviral and antimalarial drugs. Effects of nevirapine (NVP), efavirenz (EFV) and lopinavir/ritonavir (LPVr) on lumefantrine (LM) therapeutic concentrations and toxicity were evaluated. In a four-arm parallel study design, the blood samples of 40 participants, treated with artemether/lumefantrine (AL), were analysed. Lumefantrine Cmax was increased by 32% (p = 0.012) and 325% (p < 0.0001) in the NVP and LPVr arms respectively but decreased by 62% (p < 0.0001) in the EFV-arm. AUC of LM was, respectively, increased by 50% (p = 0.27) and 328% (p < 0.0001) in the NVP and LPVr arms but decreased in the EFV-arm by 30% (p = 0.019). Median day 7 LM concentration was less than 280 ng/mL in EFV-arm (239 ng/mL) but higher in control (290 ng/mL), NVP (369 ng/mL, p = 0.004) and LPVr (1331 ng/mL, p < 0.0001) arms. There were no clinically relevant toxicities nor adverse events in both control and test arms. Artemether/lumefantrine is safe and effective for treatment of malaria in PLWHA taking NVP and LPVr based ART regimen but not EFV-based regimen.

Bioactivity and modulatory functions of Napoleona vogelii on oxidative stress-induced micronuclei and apoptotic biomarkers in mice.

Napoleona vogelii is used in traditional medicine for the management of pain, inflammatory conditions and cancer. This study was conducted to investigate the modulatory mechanisms of methanol stem bark extract of N. vogelii on induction of micronuclei, apoptotic biomarkers and in vivo antioxidant enzymes in mice. Forty male albino mice were randomly divided into eight groups (n = 5) and were administered distilled water (DW, 5 mL/kg) as negative control, 100, 200 or 400 mg/kg of the extract respectively for 28 days before the injection of cyclophosphamide (CP, 40 mg/kg) i.p. on the 28th day. The remaining groups were administered 100, 200 or 400 mg/kg of the extract only for 28 days. Twenty four hours after injection of CP or administration of the last dose of extract, animals were euthanized by cervical dislocation and blood samples collected for determination of in vivo antioxidants, the spleen harvested for immunohistochemical expression of NFκB, Bcl-2, Bax and p53. Bone marrow smears were also made for the micronucleus assay. Treatment with the extract resulted in a significant (p < 0.0001) reduction in frequency of micronucleated polychromatic erythrocytes (MNPCEs) compared to CP exposed control conferring protection of 75.09, 94.74 and 96.84% at 100, 200 or 400 mg/kg respectively. In extract and CP exposed animals, there were significant (p < 0.05) increases in GSH, GST and SOD with a corresponding significant (p < 0.05) reduction in MDA. In addition, the extract significantly downregulated cytoplasmic levels of NFκB and Bcl-2 and upregulated Bax and p53. These findings demonstrate that N. vogelli may serve as an interesting lead for chemo-preventive drug development.

Evaluation of in-vitro and in-vivo antidiabetic, antilipidemic and antioxidant potentials of aqueous root extract of Strophanthus hispidus DC (Apocynaceae).

Background Antidiabetic activity of aqueous root extract of Strophanthus hispidus (SHP) was evaluated based on its folklore used in traditional medicine for the treatment of diabetes. Objectives: This study aimed to investigate the in-vitro and in-vivo antidiabetic potential of the aqueous root extract of SHP. Methods SHP (50, 100 and 200 mg/kg p.o.), glibenclamide (5 mg/kg p.o.), normal saline (10 mL/kg; diabetic control) and distilled water (10 mL/kg; normal control) were administered once daily for 28 days, with the measurement of fasting blood glucose level at 7 days interval. Blood samples were collected on day 28 for serum biochemical (albumin, total protein [TP], creatinine, alanine transaminase [ALT], aspartate transaminase [AST], alkaline phosphatase [ALP], triglycerides [TG], total cholesterol [TC], high-density lipoprotein [HDL], low-density lipoprotein [LDL], bilirubin and urea) and hematological assays. The in-vitro antidiabetic activity was investigated using α-amylase and α-glucosidase enzymes inhibitory assays. Results SHP produced a day-dependent reduction in glucose level. Peak reduction (82.94 %; p < 0.05) was produced at the dose of 100 mg/kg. SHP significantly (p < 0.05) increased the level of HDL and TP but significantly (p < 0.05) reduced the levels of TG, LDL, TC, AST, ALT, ALP, bilirubin, creatinine and urea compared with diabetic control rats. Furthermore, SHP significantly (p < 0.05) increased the level of catalase, superoxide dismutase and reduced glutathione compared to diabetic control rats. SHP significantly (p < 0.05) inhibited α-amylase and α-glucosidase enzymes compared with acarbose. Conclusion The findings in this study showed that SHP possesses beneficial antidiabetic activity.

Clinically Significant Drug-Drug Interaction in a Large Antiretroviral Treatment Centre in Lagos, Nigeria.

Background: An important cause of treatment failure to antiretroviral therapy (ART) is the potential interaction between the antiretroviral (ARV) drugs and co-prescribed drugs used concomitantly for the treatment of opportunistic infections and co-morbid ailments in HIV-infected patients. Objectives: The study evaluated potential clinically significant drug interactions (CSDIs) occurring between recommended ART regimens and their co-prescribed non-antiretroviral drugs (CPD) Method: This study was carried out in a large HIV treatment centre (APIN clinic) in a Nigerian teaching hospital, in Lagos Nigeria, caring for over 20,000 registered patients. Electronic Medical Records (EMR) of 500 patients  who received treatment between 2005 and 2015, were selected using systematic random sampling, reviewed retrospectively, and evaluated for potential CSDIs using Liverpool HIV Pharmacology Database and other similar databases.                                                                                                                                          Results:  Majority of patients, 421 (84%) were at risk of CSDIs, of  which  410, (82%) were moderate and frequently involved co-trimoxazole + zidovudine (or stavudine) /lamivudine (386, 77.2%) and NNRTIs or PIs + artemisinin-based combination therapies (ACTs) [296, 59.2%]. Age (p=0.131), sex (p=0.316) and baseline CD4+ cell counts (p>0.05) were not significantly associated with CSDIs. The interactions, however, were significantly associated with the development of antiretroviral treatment failure (p <0.001) which occurred in nearly a third (139; 27.8%) of the patients. Conclusion: There is a high prevalence of CSDIs between ART and CPDs most of which were categorized as moderate.  Further studies are required to evaluate the pharmacokinetic and clinical relevance of these interactions.

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

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.

Antidiabetic Effects of the Ethanolic Root Extract of Uvaria chamae P. Beauv (Annonaceae) in Alloxan-Induced Diabetic Rats: A Potential Alternative Treatment for Diabetes Mellitus.

Diabetes mellitus has been a menace to mankind from time immemorial. However, a natural product such as U. chamae P. Beauv (Annonaceae) offers alternative treatment for diabetes mellitus. The study aimed at evaluating antidiabetic activity of the ethanolic root extract of U. chamae in alloxan-induced diabetic rats. Diabetes was induced in Sprague Dawley rats after overnight fast with 150 mg/kg alloxan intraperitoneally. After 72 h, those with plasma glucose levels >200 mg/dl were classified as diabetic. Five diabetic rats in each group were treated daily for 14 days orally with 100, 250, and 400 mg/kg of the extract, glibenclamide (71 µg/kg) and pioglitazone (429 µg/kg), respectively, while another group was untreated. Control received 0.5 ml of Acacia senegal. Effects of extract on glucose, other biochemical, and hematological parameters were evaluated. α-amylase and α-glucosidase inhibitory activities of extract and its fractions were also evaluated. Percentage inhibition and IC50 values were determined. Diabetic control was achieved on the 7th day of the study with 100, 250, and 400 mg/kg of the extract showing glucose reduction of 72.14%, 78.75%, and 87.71%, respectively. The HDL-cholesterol levels of diabetic rats treated with extracts were significantly increased. Extract and its fractions caused α-amylase and α-glucosidase inhibition. Histologically, pancreas of diabetic rats treated with extract showed regenerated islet cells which were not seen in rats treated with glibenclamide and pioglitazone. This study showed that U. chamae has antidiabetic activity which may be through α-amylase and α-glucosidase inhibition and regeneration of pancreatic beta cells. Also, it may reduce the risk of cardiovascular disease by increasing HDL-cholesterol levels.

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.

Antidiabetic and hypolipidemic activities of hydroethanolic root extract of Uvaria chamae in streptozotocin induced diabetic albino rats.

BACKGROUND: Diabetes mellitus is a metabolic disorder of multiple aetiology characterised by hyperglycemia resulting from defects in insulin secretion, insulin action or both. It is a global epidemic ravaging both developed and developing countries. The situation will worsen if nothing is done urgently. In fact, the need to identify natural products with antidiabetic potentials is of great importance as supported by several research efforts all over the world, in search of antidiabetic plant based products that are safe and efficacious. Available literatures show that several phytochemicals with antidiabetic properties have been identified in certain plants amongst which include Uvaria chamae. The potentials of Uvaria chamae as an antidiabetic and hypolipidemic drug-candidate are thus tested. METHODS: Diabetes mellitus was experimentally induced after the rats were fasted overnight by administering intraperitoneally, 60 mg/kg streptozotocin. After 72 h, the rats with plasma glucose levels >200 mg/dl were classified as diabetic. A total of six groups containing five rats per group were used. One group of diabetic rats was untreated. Three diabetic groups, each were treated orally with 100, 250 and 400 mg/kg body weight of the extract. Another diabetic group was treated with insulin (0.5 IU/kg) subcutaneously. The control received 0.5 ml (2% solution) of acacia orally. The treatment was for 8 days. The effects of the extract on weight, plasma glucose and other biochemical parameters were evaluated using standard procedures. RESULTS: The diabetic rats treated with the extract showed significant reductions (p < 0.05) in weight, plasma glucose levels, low density lipoprotein and cholesterol compared with the control. The 100, 250 and 400 mg/kg body weight of the extract showed maximum glucose reduction of 85.16, 81.50 and 86.02% respectively. Histologically the pancreas of the diabetic rats treated with the extract, showed clusters of variably sized regenerated islet of Langerhans within sheets of normal exocrine pancreas, while the pancreas of diabetic rats treated with insulin showed no islet of Langerhans. CONCLUSION: The study showed that Uvaria chamae caused weight loss and has good hypoglycemic and hypolipidemic activities that may reduce the risk of developing cardiovascular diseases.

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.

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

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.

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.

Antihyperglycemic profile of erinidine isolated from Hunteria umbellata seed.

Water decoction made from the seed of Hunteria umbellata is widely used in the traditional management of diabetes mellitus by Nigerian herbalists, particularly, in the southwest region of the country. Recently, a new bisindole alkaloid, erinidine, was isolated but its antihyperglycemic profile remains largely un-investigated scientifically. This forms the basis for the current study which is primarily designed at investigating the antihyperglycemic profile of erinidine and other fractions in both in vitro and in vivo models of diabetes mellitus. In the present study, erinidine was isolated and purified using the earlier described methods and its antihyperglycemic potentials tested in in vitro models such as dipeptidylpeptidase (IV), glycogen phosphorylase, HIT-T15 cell insulin secretion, glucose uptake activity, aldose reductase assays and α-glucosidase inhibition assay testings. In addition, 50 mg/kg of erinidine and that of other fractions were evaluated in in vivo models of normal and chemically-induced hyperglycemic rats. Results showed that erinidine was a light yellow, amorphous solid with UV (CHCl3) λ max 256 nm, HRESIMS m/z 382.1881 [(M+H)(+)] (calculated for C22H26N4O2, 382.1876) and melting point of 230 °C. The in vitro study showed the antihyperglycemic action of erinidine to be weakly mediated via α-glucosidase inhibition mechanism as the results for other in vitro tests such as dipeptidylpeptidase (IV), glycogen phosphorylase, HIT-T15 cell insulin secretion, glucose uptake activity and aldose reductase assays were all negative. However, the in vivo results showed 50 mg/kg erinidine given per os to normal and alloxan-induced hyperglycemic rats to significantly (p<0.05, p<0.001) attenuate an increase in their post-absorptive blood glucose concentrations after 3 g/kg glucose loading in the rats, suggesting its antihyperglycemic mechanism to be via α-glucosidase inhibition. This result, although, further corroborated the in vitro findings but also suggests that erinidine needs to be biotransformed in vivo for its inhibitory activity on intestinal glucose absorption to become evident. Thus, the present study suggests erinidine to be the possible antihyperglycemic agent in Hunteria umbellata seed extract mediating its antihyperglycemic action via intestinal glucose uptake inhibition.

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

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.

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.

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 Ca(2+) 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.