Evaluation of the diuretic activity of the aqueous and 80% methanol extracts of Ajuga remota Benth (Lamiaceae) leaves in mice

BACKGROUND: In the Ethiopian traditional medicine, the leaves of Ajuga remota B. (Local name, Armagusa) is used in the treatment of hypertension. Since this claim has not been investigated scientifically, the aim of the present study was to evaluate the diuretic potential of the aqueous and 80% methanol extracts of the leaves of Ajuga remota in mice after acute oral administration. METHODS: Adult mice were administered orally either aqueous (250 mg/kg, AA250; 500 mg/kg, AA500 and 1000 mg/kg, AA1000) or 80% methanol (250 mg/kg, AM250; 500 mg/kg, AM500 and 750 mg/kg, AM750) extract. Urine output and electrolyte contents were then quantified up to 5 h and compared with those administered with furosemide 10 mg/kg (F10) and distilled water (CON). RESULTS: The larger dose of 80% methanol extract produced significant diuresis (p < 0.01), while the aqueous extract had shown diuresis both at the middle (p < 0.01) and higher (p < 0.01) doses by the end of the fifth hour compared to CON mice. Regarding electrolyte excretion, larger doses of both extracts had increased natriuresis (p < 0.001 for AA1000 and p < 0.01 for AM1000), while the effect on kaliuresis were smaller when compared with the standard, suggesting the plant could possibly have a potassium-sparing effect. Phytochemical screening revealed the presence of secondary metabolites like phenolic compounds, tannins, saponins, flavonoids, terpenoids, steroids, and cardiac glycosides, which might account for the diuretic activity. CONCLUSIONS: The results indicate that the plant is endowed with significant diuretic activity at various doses, providing evidence for its folkloric use. The major components like flavonoids, tannins, terpenoids and alkaloids found in the plant might have contributed to the observed diuretic activity

The Effect of Acute and Subchronic Administration of Crude Khat Extract (Catha Edulis F.) on Weight in Mice

People widely chew khat, particularly in East Africa, for different purposes but there is no consistent data showing its effect on anorexia and weight. This study was made to add to the existing body of knowledge about khat and its effect on weight. A total of 50 albino mice, 6-8 weeks old, were administered orally with a single daily dose of khat extract for 30 days. The animals were divided into 4 groups. The first group served as controls and was administered with 0.5 ml 3% Tween 80 in water. Group two (K100), three (K200) and four (K300) were administered 100, 200 and 300 mg/kg khat extract, respectively.  The effect of crude khat extract on weight was measured and analyzed using One-way ANOVA. The result showed that acute administration of crude khat extract at doses used did have a significant effect on weight on all the three groups (khat administered) (p&lt; 0.01) but there was no significant weight difference among the three groups. After the fourth days, this weight decrease, however, was followed by regaining the initial weight and then increasing till the end of the experiment.  Crude khat extract at acute and sub-chronic administration have anorexic effect but followed by development of tolerance which may be explained by a complex of Neuro-chemical processes

Review of ethnobotanical and ethnopharmacological evidences of some Ethiopian medicinal plants traditionally used for the treatment of cancer

Background: Ethiopia is endowed with enormous diversity of plants. However, the majority of these plants have not been scientifically investigated. Traditional knowledge on the use of plants as medicinal agents has been transferred from generation to generation, as guarded secrets, through the word of mouth, and scientific studies on these herbs have not been properly compiled.Objectives: The main objective of this study was to review published ethnobotanical and ethnopharmacological evidences of Ethiopian medicinal plants with anticancer potentials.Material and methods: A total of 92 articles have been reviewed. They were obtained from search engines such as PubMed, Science Direct and Google Scholar. The following keywords were used to search for the literature inside the databases: plant extract, anticancer, Ethiopia, antioxidant compounds, cytotoxic compounds and in vivo toxicity.Results: The current literature review revealed that about 136 anticancer plants belonging to 57 families have been identified in Ethiopia. Among these, 98 plant species were reported for their traditional use to treat different types of symptomatic cancers. However, only 29 species were scientifically studied for their in vitro cytotoxic or free radical scavenging activities. Plant parts commonly used for preparation of anticancer remedies were leaves (41.4%) and roots (32.8%). Among the reported plant species, whilst the crude extracts of Artemisia annua, Acokanthera schimperi and Catha edulis were found to be potent cytotoxic agents (IC50&lt;15 g/ml), the total extracts of Cassia arereh, Rubus steudneri and Thymus schimperi showed strong radical scavenging activity (IC50 &lt;15 g/ml). Chronic administration of Syzygium guineense hydroalcoholic leaf extract, on the other hand, induced pathological changes in liver and kidney of mice.Conclusions: Although several Ethiopian plants traditionally used for the treatment of cancer were shown to possess cytotoxic and free radical scavenging activities, in most cases compounds responsible for such activities have not been identified. Therefore, activity-guided detailed phytochemical studies coupled with evaluation of the safety particularly on those plant extracts that demonstrated potent activities should be carried out as this may lead to the discovery of safe and cost effective anticancer agents. [Ethiop. J. Health Dev. 2017;31 (3):161-187]Keywords: Ethiopian medicinal plants, Antioxidant, Anticancer, Ethnopharmacology, Traditional us

Effects of Khat (Catha edulis) use on catalytic activities of major drug-metabolizing cytochrome P450 enzymes and implication of pharmacogenetic variations

En un estudio cruzado unidireccional, investigamos el efecto del Khat, una planta psicoestimulante natural similar a las anfetaminas, en las actividades catalíticas de cinco importantes enzimas del citocromo P450 (CYP) que metabolizan las drogas. Tras una semana de abstinencia de Khat, se fenotipó a 63 varones voluntarios etíopes utilizando drogas de sonda de cóctel (cafeína, losartán, dextrometorfano, omeprazol). El fenotipado se repitió después de una semana de uso diario de 400 g de hojas frescas de Khat. Se hizo el genotipado para CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A5. Se cuantificaron las concentraciones de catinona y fenilpropanolamina urinarias, y de drogas de sonda de plasma y metabolitos mediante LC-MS/MS. Se evaluó el efecto del Khat en las actividades enzimáticas comparando las proporciones metabólicas (MR) de cafeína/paraxantina (CYP1A2), losartán/ácido carboxílico losartán (CYP2C9), omeprazol/5-hidroxiomeprazol (CYP2C19), dextrometorfano/dextrorfano (CYP2D6) y dextrometorfano/3-metoximorfano (CYP3A4) antes y después del uso del Khat. La prueba del par de Wilcoxon indicó un aumento significativo en la mediana de la RM de CYP2D6 (41%, p < 0,0001), y un aumento marginal en la RM de CYP3A4 y CYP2C19 por el Khat. La medida repetida ANOVA indicó el impacto del genotipo CYP1A2 y CYP2C19 en las interacciones de las enzimas Khat-CYP. La mediana de la RM aumentó un 35% en CYP1A2*1/*1 (p = 0,07) y un 40% en los portadores de alelos CYP2C19 defectuosos (p = 0,03). Las proporciones logarítmicas de catinona/fenilpropanolamina en la orina se correlacionaron significativamente con el genotipo CYP2D6 (p = 0,004) y la RM de CYP2D6 (p = 0,025). El khat inhibe significativamente el CYP2D6, inhibe marginalmente el CYP3A4 y, dependiendo del genotipo, inhibe las actividades enzimáticas del CYP2C19 y el CYP1A2.In a one-way cross-over study, we investigated the effect of Khat, a natural amphetamine-like psychostimulant plant, on catalytic activities of five major drug-metabolizing cytochrome P450 (CYP) enzymes. After a one-week Khat abstinence, 63 Ethiopian male volunteers were phenotyped using cocktail probe drugs (caffeine, losartan, dextromethorphan, omeprazole). Phenotyping was repeated after a one-week daily use of 400 g fresh Khat leaves. Genotyping for CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A5 were done. Urinary cathinone and phenylpropanolamine, and plasma probe drugs and metabolites concentrations were quantified using LC-MS/MS. Effect of Khat on enzyme activities was evaluated by comparing caffeine/paraxanthine (CYP1A2), losartan/losartan carboxylic acid (CYP2C9), omeprazole/5-hydroxyomeprazole (CYP2C19), dextromethorphan/dextrorphan (CYP2D6) and dextromethorphan/3-methoxymorphinan (CYP3A4) metabolic ratios (MR) before and after Khat use. Wilcoxon-matched-pair-test indicated a significant increase in median CYP2D6 MR (41%, p < 0.0001), and a marginal increase in CYP3A4 and CYP2C19 MR by Khat. Repeated measure ANOVA indicated the impact of CYP1A2 and CYP2C19 genotype on Khat-CYP enzyme interactions. The median MR increased by 35% in CYP1A2*1/*1 (p = 0.07) and by 40% in carriers of defective CYP2C19 alleles (p = 0.03). Urinary log cathinone/phenylpropanolamine ratios significantly correlated with CYP2D6 genotype (p = 0.004) and CYP2D6 MR (P = 0.025). Khat significantly inhibits CYP2D6, marginally inhibits CYP3A4, and genotype-dependently inhibit CYP2C19 and CYP1A2 enzyme activities.• Swedish Research Council. Proyecto VR 2015–03295 • Instituto de Salud Carlos III-Sara Borrell. Programa CD13/00348, para Fernando de Andrés SegurapeerReviewe

Affordability of commonly prescribed antibiotics in a large tertiary teaching hospital in Ethiopia: a challenge for the national drug policy objective

Objective In national drug policies of many countries, ensuring availability and affordability of essential medicines is indicated among the major policy objectives. To achieve the objectives, countries with low and middle income compile such medicines into NEMLs. This study aims to determine availability and affordability of commonly prescribed antibiotics at a tertiary hospital in Ethiopia by assessing (in private and public pharmacies) 13 antibiotics constituting DU90% at the hospital. Results Availability of the antibiotics in the private and public pharmacies was 92.3% and 98.5%, respectively. Average MPRs for the antibiotics were 4.1 and 2.7, respectively, in the private and public pharmacies. The days’ wages (in median prices) ranged from 0.2 for treating acute diarrhea with doxycycline to 415.8 for treating HAP in public pharmacies. Costs of a single day treatment with antibiotics purchased from the public pharmacies ranged from USD 0.1 for acute diarrhea to USD 29.7 for HAP. For the private pharmacies, the range was from USD 0.1 for toxoplasmosis to USD 54.9 for HAP. This study showed that treatments of commonly diagnosed infectious conditions at TASH remain unaffordable according to the WHO/HAI criteria

Effect of Extracts of Khat (Catha edulis F.) on Glucose Handling in Normoglycaemic, Diabetic, and Glucose Loaded Rodents

Khat (Catha edulis F., Celastraceae) is widely chewed for its euphoric effects and as recreational drug to improve performance. Although khat is also claimed to be useful in diabetic patients, conflicting results appear in the literature on the benefit of khat in managing diabetes. This study was therefore initiated to investigate the effect of khat on blood glucose homeostasis in rodents. Crude extract as well as flavonoid and alkaloid fractions of khat were used to investigate its effect in normoglycaemic, diabetic, and oral glucose loaded animals. Three doses of crude extract (100, 200, 400 mg/kg), four doses of flavonoid fraction (50, 100, 200, 400 mg/kg), and one dose of alkaloid fraction (200 mg/kg) were employed. Positive and negative controls were treated with 5 mg/kg glibenclamide and 2% Tween-80, respectively. Fractions and doses that provided prominent activity in diabetic mice were selected for oral glucose tolerance test. Blood was then taken from the tail vein at 0, 1, 2, 3 and 4 h to determine blood glucose level using commercial one touch glucometer. The flavonoid fraction at 200 and 400 mg/kg (p &lt; 0.001) as well as the alkaloid fraction (p &lt; 0.05) and glibenclamide (p &lt; 0.05) produced a significant reduction in blood glucose level in normoglycaemic mice compared to the negative control. In diabetic mice, significant decline (p &lt; 0.05) was noted with 400 mg/kg of the crude extract, 50, 100 and 400 mg/kg of the flavonoid fraction, and glibenclamide. In glucose loaded rats, 400 mg/kg of the crude extract was the only group that significantly lowered (p &lt; 0.05) blood glucose level in comparison to vehicle-treated animals. Higher dose of the crude extract was shown to possess antidiabetic activity without producing hypoglycaemia. Antidiabetic effect could be primarily, if not exclusively, linked to the flavonoidal contents. However, since the flavonoid and alkaloid fractions were associated with hypoglycaemia, this effect seems to be counterbalanced by other constituents.Keywords: Catha edulis, flavonoids, alkaloids, blood glucose, diabete

Evaluation of the antidepressant-like activity of solvent fractions of the aerial parts of Hypericum revolutum (Hypericaceae) in rodent models

Various species of the genus Hypericum have been traditionally used for different purposes. A previous study showed that 80% methanol extract of Hypericum revolutum was active in animal model of depression. The present study was performed on solvent fractions of the crude extract as part of the effort to develop a candidate drug from the plant. The fractions (chloroform, butanol and aqueous) were prepared using liquid-liquid extraction from 80% methanol extract. Antidepressant-like activity of the fractions was investigated at various doses (100, 200 and 400 mg/kg) using a host of paradigms, including forced swim test (FST), tail suspension test (TST) and open field test (OFT). Moreover, preliminary phytochemical screening and finger printing using thin layer chromatography were undertaken. Promising antidepressant-like activity was detected with 200 mg/kg and 400 mg/kg (p &lt; 0.05) of the butanol and chloroform fractions in the FST and TST. The doses did not, however, produce significant effect on spontaneous motor activity when assessed in OFT. The aqueous fraction was devoid any activity. The findings indicate that the higher doses of chloroform and butanol fractions possess antidepressant-like activity as evidenced by significant decrease in the duration of immobility in the two paradigms. These effects of fractions were displayed without significant effect on locomotor activity, suggesting that the antidepressant-like activity observed is not caused by a non-specific motor stimulation. In addition, the preliminary phytochemical screening indicated that the fractions contained different secondary metabolites previously reported to have antidepressant-like effects.Keywords: Hypericum revolutum, anti-depressant activity, solvent fractions, forced swimming test, tail suspension tes

Adherence and treatment outcome among epileptic patients of follow-up at Amanuel Specialized Mental Hospital, Ethiopia

Epilepsy is treated with anti-epileptic drugs, aiming at controlling seizure without inducing adverse effects. The literature is sparse in treatment outcome of epileptic patients in resource poor settings. The aim of this study was therefore to assess adherence and treatment outcome among epileptic patients. A cross-sectional study was conducted among epileptic patients on follow-up at Amanuel Specialized Mental Hospital (ASMH). Patients who had follow up for at least two years were recruited and adherence and treatment outcome were evaluated through chart review and patient interview. Factors affecting adherence and seizure control were also determined using regression analysis. A total of 397 patients were evaluated, out of which 61% were males. Generalized tonic clonic seizure was the predominant (76.1%) form of seizure diagnosed. A large proportion of patients were managed with monotherapy (74.8%), phenobarbitone being the most commonly (60.5%) used single agent. About 70% of patients were adherent to treatment, but only 38.6% of the patients were seizure free for at least two years. Seizure free period and year of follow up were found to have significant association with adherence. Number of drugs, side effect burden, adherence and educational levels were found to have a significant association with seizure control status. The findings collectively indicate that health care providers should focus on adherence, treatment modality and side effect burden to control seizure. In addition, there must be a consideration of clinical assessment to withdraw treatment for those patients who were seizure free for at least two years. Keywords: anti-epileptic drugs, epilepsy, treatment outcome, adherence, cross-sectional stud