Anti-Convulsant Activity of Soxhlet Leaf Extracts of Ajuga Integrifolia Buch.-Ham. Ex D.Don (Lamiaceae) in Mice.

Background: The leaves of Ajuga integrifolia Buch.-Ham. ex D.Don (Lamiaceae) have long been used as an anti-convulsant remedy in Ethiopian traditional medicine. However, the evidence supporting their use is sparse in the literature. This study was conducted to add to the existing body of knowledge about the anti-convulsant activity of the plant. Methods: The anti-convulsant activity of the extract was investigated in both acute (pentylenetetrazol [PTZ], 80 mg/kg; and maximal electroshock [MES]) and chronic (PTZ, 35 mg/kg) kindling seizure models. For the experimental paradigms, various doses of the extract (100, 200, and 400 mg/kg) were administered. Positive controls received sodium valproate (200 mg/kg) for the PTZ model and phenytoin (25 mg/kg) for the MES model. Parameters including the onset of clonus and duration of hindlimb tonic extension were recorded and compared with controls. Moreover, the total alkaloid, flavonoid, and phenol contents of the extracts were determined. Results: Ethyl acetate extract produced a superior effect among all solvent extracts in both the PTZ and MES models. At all doses, it significantly delayed the mean onset of clonus (p<0.01) in the PTZ test compared to controls. It also significantly reduced (p<0.001) the mean duration of hindlimb tonic extension in the MES model. Treatment of mice with 200 mg/kg (p<0.01) and 400 mg/kg (p<0.001) of ethyl acetate extract significantly protected against PTZ-induced kindling compared to controls. The leaf was found to contain 10.002±0.119 mg atropine equivalent per gram of dry extract of alkaloids, 9.045±0.8445 mg quercetin equivalent per gram of dry extract of flavonoids, and 21.928±1.118 mg gallic acid equivalent per gram of dry extract of phenols. Conclusion: This study indicated that the plant A. integrifolia has anti-convulsant activity in both acute and chronic models of seizure. This plant represents a potential source for the development of a new anti-epileptic drug for pharmacoresistant epilepsy.

Antidiarrheal and Antibacterial Activities of Calpurnia aurea: Benth Seed Different Extracts.

Background: Calpurnia aurea is believed to have antidiarrheal potential but with limited scientific evidence. This study aimed investigating antidiarrheal and antibacterial activity of aqueous and 80% methanol seed extracts of the plant in mice and selected diarrhea-causing bacterial strains, respectively. Methods: Castor oil-induced diarrhea, prostaglandin-induced enteropooling, and castor oil-induced charcoal meal test models in mice of either sex using three dose levels (60, 120, and 240 mg/kg) were applied to evaluate antidiarrheal activity. Parameters, including onset, number, wet stool weight, weight and volume of secretion, and intestinal motility, were taken into consideration. The antibacterial activity was assessed on Shigella soni, Salmonella typhimurium, Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa using disk diffusion and microdilution techniques. Results: Compared to controls, pretreatment of mice at the graded dose (60, 120, and 240 mg/kg) resulted in a significant (p < 0.05) drop in frequency of wet stools and watery content of diarrhea as well as in delaying onset of diarrhea. Both extracts exhibited inhibition of diarrhea in a dose-dependent manner in all models used. The extracts also showed significant (p < 0.05) reduction in intestinal motility in castor oil-induced models. Both extracts showed a marginal activity against the selected bacterial strains; a better effect was seen with 80% methanol seed extract. Conclusion: Both extracts of the plant have beneficial effect in controlling diarrhea. This finding supports the use of the plant as a traditional antidiarrheal remedy.

In Vivo Anti-Malarial Activity of the Aqueous Root Extract of Euclea divinorum Hiern (Ebenaceae) against Plasmodium berghei ANKA.

Background: Drug resistance is a universal challenge to malaria control measures. As a result, the development and discovery of new chemotherapeutic agents from medicinal plants having anti-malarial traditional claims are very important. This work, therefore, attempted to evaluate the anti-malarial activity of the aqueous root extract of E. divinorum using a rodent model of malaria. Methods: The roots of E. divinorum were extracted by hot decoction using distilled water. Anti-malarial activity of various doses (100 mg/kg, 200 mg/kg, and 600 mg/kg) of the root aqueous extract was evaluated using the 4-day suppressive test as well as curative and repository tests. Parasitemia, rectal temperature, body weight, PCV, and MST were also determined. Results: The finding showed that there were a dose-related significant parasitemia chemo-suppression and increment in survival time as compared to the negative control (p < 0.001) in all tests. The chemo-suppression effect was higher at 400 mg/kg extract-treated groups in the 4-day suppressive test followed by the curative test. The lowest chemo-prophylaxis effect was observed in 100 mg/kg extract-treated groups in the repository test. Regarding the other parameters, the extract prevented weight loss, temperature drop, and hemolysis in all models but not in a consistent manner. Conclusion: The current study showed that the aqueous root extract of E. divinorum possessed a varying degree of anti-malarial activity in all three tests, with greater parasitemia suppression observed in the 4-day suppressive test. The extract produced higher parasitemia chemo-suppression and longer survival time in early infections followed by established and then residual infection.

The impact of catha edulis (vahl) forssk. ex endl. (celestraceae) (khat) on pharmacokinetics of clinically used drugs.

INTRODUCTION: Catha edulis (Vahl) Forssk. ex Endl. (Celestraceae) is used as a recreational drug on daily basis for its euphoric and psychostimulant effects. It is also chewed by individuals who are on medications, raising the possibility of drug-khat interaction. However, limited data are available in the literature, although clinically significant interactions are expected, as khat contains a complex mixture of pharmacologically active constituents. AREAS COVERED: It provides an overview of the phytochemistry, pharmacokinetics, pharmacodynamics, and pharmacogenetics of khat based on the literature mined from PubMed, Google Scholar, and Cochrane databases. It also presents a detailed account of drug-khat interactions with specific examples and their clinical significance. The interactions mainly occur at the pharmacokinetics level and particular attention is paid for the phases of absorption and cytochrome P450 enzyme-mediated metabolism. EXPERT OPINION: Despite the increasing trend of khat chewing with medications among the populace and the potential risk for the occurrence of clinically significant interactions, there is paucity of data in the literature demonstrating the magnitude of the risk. The available data, however, clearly demonstrate that the consequence of drug-khat interaction is dependent on genotype. Genotyping, where feasible, could be used to improve clinical outcome and minimize adverse reactions.

Ethiopian Medicinal Plants Traditionally Used for the Treatment of Cancer; Part 3: Selective Cytotoxic Activity of 22 Plants against Human Cancer Cell Lines.

Medicinal plants have been traditionally used to treat cancer in Ethiopia. However, very few studies have reported the in vitro anticancer activities of medicinal plants that are collected from different agro-ecological zones of Ethiopia. Hence, the main aim of this study was to screen the cytotoxic activities of 80% methanol extracts of 22 plants against human peripheral blood mononuclear cells (PBMCs), as well as human breast (MCF-7), lung (A427), bladder (RT-4), and cervical (SiSo) cancer cell lines. Active extracts were further screened against human large cell lung carcinoma (LCLC-103H), pancreatic cancer (DAN-G), ovarian cancer (A2780), and squamous cell carcinoma of the esophagus (KYSE-70) by using the crystal violet cell proliferation assay, while the vitality of the acute myeloid leukemia (HL-60) and histiocytic lymphoma (U-937) cell lines was monitored in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) microtiter assay. Euphorbia schimperiana, Acokanthera schimperi, Kniphofia foliosa, and Kalanchoe petitiana exhibited potent antiproliferative activity against A427, RT-4, MCF-7, and SiSo cell lines, with IC50 values ranging from 1.85 ± 0.44 to 17.8 ± 2.31 µg/mL. Furthermore, these four extracts also showed potent antiproliferative activities against LCLC-103H, DAN-G, A2780, KYSE-70, HL-60, and U-937 cell lines, with IC50 values ranging from 0.086 to 27.06 ± 10.8 µg/mL. Hence, further studies focusing on bio-assay-guided isolation and structural elucidation of active cytotoxic compounds from these plants are warranted.

Evaluation of the Diuretic Activity of Aqueous and 80% Methanol Extracts of Croton macrostachyus(Euphorbiaceae) Leaves in Saline-Loaded Rats.

BACKGROUND: Croton macrostachyus (Euphorbiaceae) extract is a folk medicine traditionally used for treating a number of disorders, including edematous conditions. The present study aimed to evaluate the diuretic effects of aqueous and 80% methanol leaf extracts of Croton macrostachyus in saline-loaded rats. METHODS: Rats of either sex were randomly assigned into eight groups of eight animals per group. The animals were treated with vehicle (distilled water), standard (furosemide 10 mg/kg), and three doses (100, 200, and 400 mg/kg) of aqueous and 80% methanol leaf extracts after loading of normal saline (15 mL/kg). Then, urine volume, electrolyte concentration, and pH were measured as parameters of evaluation. Concentrations of urinary Na+ K+, and Cl- were determined and Na+:K+ and Cl-:Na+ + K+ ratios calculated to reveal possible mechanisms. RESULTS: The aqueous extract at 200 mg/kg had produced significant diuresis by hour 3, while the same dose of 80% methanol extract had produced substantial diuresis by the end of hour 4. Both extracts at 400 mg/kg produced significant diuresis from hour 2 to hour 5. In terms of effect on electrolysis, 400 mg/kg aqueous extract produced significant natriuresis, and a kaliuresis effect was observed for both extracts at higher doses and 200 mg/kg aqueous extract. CONCLUSION: The findings collectively indicated that both aqueous and 80% methanol extract showed significant diuretic activity, thereby justifying the plant's traditional use as a diuretic agent.

Complete symptom resolution as predictor of Helicobacter pylori eradication and factors affecting symptom resolution: Prospective follow up study.

BACKGROUND: Symptom resolution is the most common clinical practice during assessment and evaluation of helicobacter pylori infected patients after employing eradication therapy. OBJECTIVE: Prediction of eradication of H. pylori with symptom resolution and assess factors affecting symptom resolution. METHOD: Facility based follow up study was done on consented H. pylori positive adult patients who received standard triple therapy consisting of a proton pump inhibitor, amoxicillin, and clarithromycin from May 2016 to April 2018 at Bahir Dar city in Ethiopia. Sociodemographic and clinical data was collected before and after eradication therapy by using pre-developed structured questionnaire. Both positive and negative predictive values were calculated. SPSS version 23 was used to conduct bivariate and backward stepwise multivariate logistic regression to analyze data. P-value < 0.05 at 95%CI was considered as significant. RESULT: The study involved a total of 421 patients who completed follow up. Patients' mean age and body weight (±SD) were 30.63 (± 10.74) years and 56.71 (± 10.19) kg, respectively. Complete symptom resolution was achieved in 84.3% of the patients and eradication of H. pylori was successful in 90% of patients. Positive predictive value of complete symptom resolution for H. pylori eradication was 98.9% (351/355) and whereas negative predictive value was 57.6%(38/66). Factors associated with complete symptom resolution were regimen completion (AOR: 2.77 95%CI (1.12-6.86), p = 0.028) and no use of traditional homemade supplements prepared from Fenugreek or Flaxseed (AOR: 2.09 95%CI (1.22-3.58), p = 0.007). CONCLUSION: Complete symptom resolution is a powerful predictor of success of H. pylori eradication and can be used to assess H. pylori status after eradication therapy. Assessment of complete symptom resolution should consider regimen completion and traditional practice of using homemade supplements prepared from Fenugreek or Flaxseed.

Methanol (80%) leaf extract of Otostegia integrifolia Benth (Lamiaceae) lowers blood pressure in rats through interference with calcium conductance.

BACKGROUND: Otostegia integrifolia Benth. (Lamiaceae) leaves are used to treat hypertension in Ethiopian folk medicine. However, the claim has so far not been investigated scientifically. Thus, the objective of this study was to evaluate the antihypertensive activity of 80% methanol leaf extract of O. integrifolia in animal model of hypertension and possible underlying mechanisms in isolated rat aorta. METHODS: Antihypertensive effect of various oral doses of the extract (250, 500 and 1000 mg/kg) was determined in fructose-induced hypertensive rats using the non-invasive tail-cuff method. Thoracic aortic strips of rats were isolated and suspended in organ bath, and the vasodepressor effect as well as the possible mechanism (s) of action were studied by means of isometric tension recording experiments ex vivo. Phytochemical analysis was also performed to suggest possible constituents related to the activity. RESULTS: Blood pressure was significantly lowered in a dose-dependent manner following extract administration, suggesting that the extract possesses antihypertensive activity. The extract also caused a dose-dependent relaxation of aortic strip precontracted with KCl at a concentration of 6.25-125 µg/L, with a maximum relaxation (100%) achieved at a cumulative concentration of 318.75 µg/ml. The relaxation mechanism was found to be independent of muscarinic receptors, prostanoids, histamine receptors, ATP dependent K+ channels, sarcoplasmic reticulum stored Ca2+ and the endothelium system. The extract shifted the Ca2+ concentration-response curve to the right similar to that caused by nifedipine, suggesting that vasorelaxation could possibly be mediated via calcium channel blockade. The extract was found to contain phenolic compounds (164.3 mg/g, expressed as gallic acid equivalents) and flavonoids (125.7 mg/g, expressed as quercetin equivalents). CONCLUSION: The findings revealed that the plant is endowed with antihypertensive activity, providing evidence for its traditional use. The effect maybe, at least in part, due to dilation of blood vessels through blockade of Ca+ 2 channels mediated by phenolic and flavonoid constituents.

Evaluation of the Antimalarial Activity of the Hydroalcoholic Extract of Leaf of Leonotis ocymifolia (Burm. f.) Iwarsson (Lamiaceae) against Plasmodium berghei in Mice.

Malaria's global impact, fueled by resistance to several antimalarial drugs, has necessitated a quest to new antimalarial drugs from several sources with traditional medicinal plants being one of them. This study was conducted to assess the antimalarial activity of a traditionally used medicinal plant, Leonotis ocymifolia, against Plasmodium berghei. The plant has been extracted using maceration technique, and doses ranging from 100-800 mg/kg of Leonotis ocymifolia were used to test its antimalarial activity. Tween 80 (2% in water) and chloroquine 25 mg/kg were used as negative and positive controls, respectively. The antimalarial activities of the plant were determined by measuring parasitemia, survival time, packed cell volume, temperature, and weight. The plant's hydroalcoholic extract, as compared to negative control, maximally decreased parasite load by 41.4% at 800 mg/kg (p < 0.001). This parasite suppression was followed by longer survival time in the groups taking 400 mg/kg (p < 0.05) and 800 mg/kg (p < 0.05) in a four-day suppressive test and in those taking 800 mg/kg (p < 0.05) in Rane's test. The plant did not prevent weight and PCV reduction but prevented temperature reduction at 400 mg/kg (p < 0.05) and 800 mg/kg (p < 0.05) in a four-day suppressive model, and at 800 mg/kg (p < 0.05) in Rane's model. The average but consistent antimalarial activity of the plant across the test models corroborates the folkloric antimalarial use of the plant. The study recommends further pharmacological screenings, isolation, and identification of active compound(s) of the plant Leonotis ocymifolia.

Ethnobotanical Study of Medicinal Plants Used by Traditional Healers to Treat Cancer-Like Symptoms in Eleven Districts, Ethiopia.

There is no ethnobotanical study conducted specifically on medicinal plants traditionally used to treat cancer in Ethiopia. Yet, traditional herbalists in different parts of the country claim that they have been treating cancer-like symptoms using herbal remedies. The objective of this study was to document medicinal plants traditionally used to treat cancer-like symptoms in eleven districts, Ethiopia. Traditional herbalists were interviewed using semistructured questionnaires, and field visits were also carried out to collect claimed plants for identification purpose. Seventy-four traditional herbalists, who claimed that they knew about and/or had used medicinal plants to treat cancer-like symptoms, were selected using the snowball method and interviewed. Herbalists used their intuition and relied on the chronicity, growth of external mass, and spreading of the disease to other parts of the body, as a means to characterize cancer symptoms. Furthermore, in some of the study districts, herbalists reported that they treat patients who had already been diagnosed in modern healthcare institutions prior to seeking help from them. The inventory of medicinal plants is summarized in a synoptic table, which contains the scientific and vernacular names of the plants, their geographical location, the parts of the plants, and the methods used to prepare the remedies. A total of 53 traditionally used anticancer plants, belonging to 30 families, were identified during the survey. The most frequently reported anticancer plants were Acmella caulirhiza Del (Asteraceae), Clematis simensis Fresen. (Ranunculaceae), Croton macrostachyus Del. (Euphorbiaceae), and Dorstenia barnimiana Schweinf. (Moraceae). Organizing traditional healers, documenting their indigenous knowledge, and scientifically validating it for the development of better cancer therapeutic agents constitute an urgent and important task for policymakers and scientists.

Antimalarial activity of the aqueous extract of the latex of Aloe pirottae Berger. (Aloaceae) against Plasmodium berghei in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: In spite of worldwide efforts, malaria remains one of the most devastating illnesses in the world. The huge number of lives it takes and the resistance of malaria parasites to current drugs necessitate the search for new effective antimalarial drugs. Medicinal plants have been the major source of such drugs and A. pirottae is one of these plants used traditionally for the treatment of malaria in Ethiopia. AIM: This study was aimed at evaluating the antimalarial activity of the aqueous extract of A. pirottae against chloroquine sensitive P. berghei in mice. MATERIALS AND METHODS: The extract was obtained by macerating the latex of A. pirottae with distilled water. To determine its antiplasmodial activity, a 4-day suppressive model was used by dividing 40 mice into five groups of 8 mice each and given 200, 400 & 600mg/kg of the extract, the standard drug (chloroquine 25mg/kg) and the vehicle (distilled water). Then parasite suppression by the extract, survival time and prevention of loss of body weight, rectal temperature and packed cell volume were assessed. All data were presented as the Mean ±â€¯SEM (Standard Error of the Mean) and analyzed using IBM SPSS version 20. RESULTS: The extract showed moderate antimalarial activity by significantly (p < 0.001) suppressing parasitemia at all dose levels with maximum parasitemia suppression of 47.0% and significantly (p < 0.01) increasing survival time. Furthermore, 400 mg/kg and 600 mg/kg doses showed significant (p < 0.01) prevention of loss in body weight, rectal temperature and packed cell volume. CONCLUSION: Based to the results of this study, A. pirottae is endowed with a moderate antimalarial activity that is in agreement with the traditional claim of A. pirottae, hence may be used as a basis for further studies to be conducted on antimalarial activity of the plant.

Involvement of CB2 Receptors in the Neurobehavioral Effects of Catha Edulis (Vahl) Endl. (Khat) in Mice.

There is behavioral evidence for the interaction between crude khat extract and the endocannabinoid system, whereby the endocannabinoid system alters khat extract-mediated behavioral effects through modulation of the monoaminergic system. The objective of this study was to investigate the role of the endocannabinoid system on the neurobehavioral effect of khat extract in mice following concomitant administration of khat extract and the CB2R agonist, JWH133. Locomotor activity test, immunohistochemistry, and reverse transcriptase polymerase chain reaction technique were utilized to assess locomotor activity, tyrosine hydroxylase immunoreactivity, and expression of dopamine transporter mRNA gene. The results show sub-acute administration of khat extract alone increased locomotor activity in mice and co-administration of the CB2R agonist, JWH133, reduced khat extract induced hyperlocomotor activity. The data revealed that cell type specific deletion of CB2Rs on dopaminergic neurons increased the hyperlocomotor behavior of khat extract. Furthermore, the results revealed that khat extract attenuated MPTP induced motor deficits, which is enhanced by JWH133. Khat extract also increased expression of tyrosine hydroxylase positive cells and expression of dopamine transporter mRNA gene in wild type mice. Nevertheless, JWH133 did not alter the effect of khat extract on tyrosine hydroxylase immunoreactivity and dopamine transporter mRNA expression when given together with khat extract. Taken together, the results suggest that the CB2Rs selectively interact with khat extract-mediated locomotor effects and could be utilized as therapeutic target in central nervous system movement disorders associated with dopamine dysregulation.

Evaluation of the anti-malarial activity of crude extract and solvent fractions of the leaves of Olea europaea (Oleaceae) in mice.

BACKGROUND: Drug resistance poses a challenge to malaria control measures. This calls for discovery & development of new chemotherapeutic agents. This study therefore was initiated to investigate the antimalarial activity of Olea europaea against Plasmodium berghei infected mice and to further ascertain in which fraction (s) the constituents responsible for anti-malarial activity are concentrated. METHODS: The leaves of Olea europaea were extracted by maceration using 80% methanol and the crude extract was then successively fractionated with solvents of differing polarity (chloroform, n-butanol and water). The anti-malarial activity of various doses of the extract and fractions (200, 400 and 600 mg/kg) was evaluated using chemo-suppressive, curative, and repository tests. Parameters, including parasitemia, rectal temperature, body weight, and packed cell volume were determined to establish the activity. RESULTS: The acute oral toxicity test result revealed that the LD50 values of the extract and fractions were greater than 2000 mg/kg in mice. The crude extract significantly reduced parasitemia (p < 0.001) and prolonged survival time (p < 0.001), in a dose-dependent manner, in all tests, as compared to the negative control group. Higher parasitemia suppression (58%) was achieved with the larger dose (600 mg/kg) in the 4-day suppressive test, suggesting that the crude extract has largely a chemo-suppressive activity. Parasitemia was significantly reduced (p < 0.001) by all fractions in all doses used when compared to the negative controls, with the rank order of n-butanol (51%) > chloroform>aqueous (21%) fractions. Larger (600 mg/kg) and middle (400 mg/kg) doses of the crude extract as well as the fractions ameliorated all the other parameters in a consistent manner, with the crude being more active than the fractions. Preliminary phytochemical analysis revealed the presence of secondary metabolites that were differentially distributed in the fractions. CONCLUSION: The findings collectively indicate that the plant is endowed with antimalarial activity, the activity being more in the crude extract than the fractions, owing to the presence of secondary metabolites that act independently or in synergy. The varying degree of antimalarial activity in the fractions suggests that non-polar and medium polar principles could be responsible for the observed activity.

In Vivo Antimalarial Activity of the 80% Methanolic Root Bark Extract and Solvent Fractions of Gardenia ternifolia Schumach. & Thonn. (Rubiaceae) against Plasmodium berghei.

BACKGROUND: Evolution of antimalarial drug resistance makes the development of new drugs a necessity. Important source in search of such drugs is medicinal plants. Gardenia ternifolia plant is used in Ethiopian traditional medicine for the treatment of malaria and is endowed with in vitro antimalarial activity. Herein, the in vivo antimalarial activity of the plant was investigated. METHODS: Acute toxicity was carried out using a standard procedure. A 4-day suppressive test was employed to evaluate the antimalarial effect of methanolic crude extract and solvent fractions of the plant. The curative and prophylactic effect of crude extract was further tested by Ranes's test and residual infection procedure, respectively, using Plasmodium berghei (ANKA strain) in Swiss albino mice. RESULTS: The chemosuppressive effect exerted by the crude extract and fractions ranged between 30-59% and 14-51%, respectively. Curative and prophylactic effects of the crude extract were in the range of 36-63% and 24-37%, respectively. All dose levels of the crude extract prevented loss of weight, reduction in temperature, and anemia on early and established infection. Butanol and chloroform fractions also did reverse reduction in temperature, body weight, and packed cell volume. CONCLUSIONS: The results indicated that the plant has a promising antiplasmodial activity and it could be considered as a potential source to develop new antimalarial agents.

Genotoxicity study of Ethiopian medicinal plant extracts on HepG2 cells.

BACKGROUND: Most of herbal medicines are used without any standard safety and toxicological trials although common assumption is that these products are nontoxic. However, this assumption is incorrect and dangerous, so toxicological studies should be done for herbal drugs. Although Pterolobium stellatum, Otostegia integrifolia and Vernonia amygdalina root extracts are frequently used in Ethiopian traditional medicine, there are no evidences of their active toxic compounds. Therefore, we made an effort to assess probable genotoxic effect of these plant extracts on DNA of human hematoma (HepG2) cells using alkaline comet assay. METHODS: Genotoxic effects of extracts were evaluated using single cell gel electrophoresis (SCGE) method on HepG2 cell. Regarding comet data, the average mean tail intensities (TI) from each individual experiment and treatment (usually at least 3 cultures/treatment) were pooled and the average mean TI was used as an indicator of DNA damage and the standard error of mean (SEM) as the measure of variance. RESULTS: DNA damage in the form of comet tail has been observed for 1 and 0.5 mg/ml P. stellatum chloroform and 80% methanol extracts on HepG2 cells, respectively. The chloroform extract of P. stellatum showed increased tail DNA percentage in a concentration dependent manner. Comet tail length in the chloroform P. stellatum extract treated cells (1 mg/ml) was significantly higher by 89% (p < 0.05) compared to vehicle treated controls. The rest of test extracts seemed to be without genotoxic effect up to a concentration of 0.5 mg/ml. CONCLUSIONS: Our findings show that two extracts from one plant evaluated have a genotoxic potential in vitro which calls for a more thorough safety evaluation. Such evaluation should include other end-points of genotoxicity apart from DNA damage, and possibly also pure compounds.

Pharmacological and Toxicological Effects of Catha edulis F. (Khat).

Khat chewing is deeply rooted in the culture and tradition of communities in khat belt countries, and its consumption is spread to other countries through the suitcase trade. The aim of this article is to review current knowledge on the chemistry, social, pharmacology and toxicology of khat and its use. Khat produces effect invariably in every system, which is harmful or beneficial in some instances. Harmful effects are observed in heavy users, although firm evidence is lacking. Chewing khat acutely elicits states of euphoria, which is followed by low mood. Khat contains alkaloids with psychostimulant properties, but the effect cannot be totally explained by these alkaloids. It is also not clear whether the effect produced in some organs like liver could be attributed to khat or pesticides sprayed during farming. Although the evidence indicates that khat has adverse effects in most organs, our understanding of the complex interaction between use and effect is incomplete, and causal relationships have not yet been described. Moreover, khat has positioned itself well in the social, economic and political arena. Thus, a multidisciplinary research is required to understand the different dimensions and come up with ways that maximize the benefit while minimizing the risk. Copyright © 2017 John Wiley & Sons, Ltd.

Evaluation of the anti-diarrheal activity of the aqueous stem extract of Lantana camara Linn (Verbenaceae) in mice.

BACKGROUND: Diarrheal disease remains a public health problem in developing countries, including Ethiopia. In order to alleviate this disease, Ethiopian traditional healers use a wide range of medicinal plants from which Lantana camara is one of them. The stem of this plant is traditionally used for the treatment of diarrhoea. In addition, this plant is scientifically evaluated to have an antispasmodic effect on in vitro study. The aim of this study was to evaluate the antidiarrheal activity of the aqueous stem extract of L. camara Linn in mice. METHODS: The antidiarrheal activity of the extract was investigated using castor oil induced diarrhoea, enteropooling and small intestine transit models. The test groups received various doses (100, 200, and 400 mg/kg) of the extract, whereas positive controls received Loperamide (3 mg/kg) and negative controls received distilled water (10 ml/kg). RESULTS: In castor oil induced diarrhoea model, the extract, at all test doses, significantly (p < 0.001) prolonged diarrhoea onset, decreased the frequency of defecation, and weight of faeces. Similarly, the extract produced a significant (p < 0.001) decline in the weight and volume of intestinal contents at all tested doses. In addition, a significant (P < 0.001) reduction in the gastrointestinal motility in charcoal meal test was also observed in all doses of the extract. Phytochemical screening of the extract revealed the presence of flavonoids, alkaloids, tannins, and phytosterols that may play a key role in its antidiarrheal activity. CONCLUSION: The obtained results of the present study confirm antidiarrheal activity of the stem of L. camara, thus provide the scientific basis for the traditional uses of this plant as a treatment for diarrhoea.

Analgesic and anti-inflammatory activities of 80% methanol root extract of Jasminum abyssinicum Hochst. ex. Dc. (Oleaceae) in mice.

BACKGROUND: Pain and inflammation are associated with the pathophysiology of various clinical conditions. Most analgesic and anti-inflammatory drugs available in the market present a wide range of problems. The current study was aimed at investigating the analgesic and anti-inflammatory activity of 80% methanol extract of J. abyssinicum root. METHODS: The analgesic activity was determined using tail-flick test and acetic acid induced writhing, whereas anti-inflammatory activity was determined by carrageenan induced paw edema and formalin induced pedal edema, carried out in vivo. The test group received three different doses of the extract (50mg/kg, 100mg/kg and 200mg/kg) orally. The positive control group received diclofenac (10mg/kg), aspirin (100mg/kg or 150mg/kg) or morphine (20mg/kg) orally. The negative control group received vehicle (2% Tween 80, 10ml/kg) orally. Furthermore, preliminary phytochemical screening was carried out. RESULTS: Oral administration of J. abbysinicum 80% methanol extract (at all doses) significantly (p<0.001) inhibit pain sensation in the pain models. Similarly, the extract demonstrated anti-inflammatory effect in the inflammation models in mice. Preliminary phytochemical screening showed the presence of saponins, flavonoids, terpenoids, triterpenens and glycosides. CONCLUSION: The data obtained from the present study indicates that the extract possessed a significant analgesic and anti-inflammatory activity, upholding the folkloric use of the plant.

Evaluation of the antimycobacterial activity of crude extracts and solvent fractions of selected Ethiopian medicinal plants.

BACKGROUND: Tuberculosis (TB) is a global health problem complicated by drug resistance and human immunodeficiency virus that has dramatically increased active TB. Several medicinal plants are used traditionally to treat TB in Ethiopia and investigating these plants is required as plants are an alternative source for development of new anti-TB drugs. The purpose of this study was to investigate antimycobacterial activity of crude extract of Carissa edulis, Otostegia integrifolia, Persea americana, Pterolobium stellatum and Vernonia amygdalina as well as fractions of the most active crude extract. METHODS: The effect of various doses of the crude extracts as well as solvent fractions on M. tuberculosis H37Rv and/or MDR-TB clinical isolate was determined using broth microdilution and microtiter resazurin assay methods. Minimum inhibitory concentration was determined by CFU count and resazurin color change observation. RESULTS: Chloroform and 80% methanol extracts of P. stellatum and O. integrifolia as well as 80% methanol and acetone extracts of P. americana had significant antimycobacterial activity (p < 0.001) against M. tuberculosis H37Rv. Chloroform extract of V. amygdalina and C. edulis didn't, however, show any significant activity compared to negative controls. P. stellatum chloroform extract was the most active on M. tuberculosis H37Rv (MIC 0.039 mg/ml) and AOZ8W-4 (MDR-TB clinical isolate) (MIC = 0.078 mg/ml). Ethyl acetate fraction of P. stellatum chloroform extract was the most active fraction. CONCLUSION: P. stellatum, O. integrifolia and P. americana were found to be endowed with antimycobacterial activity. However, P. stellatum appears to be the most promising plant based on criteria set by different studies. Ethyl acetate fraction of P. stellatum was found to be the most active and future studies should involve this fraction.

Evaluation of the antidiarrheal activity of the leaf extracts of Myrtus communis Linn (Myrtaceae) in mice model.

BACKGROUND: Myrtus communis L. has a folkloric repute for the management of diarrhea and dysentery in different parts of the world. However, the safety and efficacy of the leaf extract have not been scientifically validated in animal model. This study was, therefore, aimed to investigate the antidiarrheal effect of 80% methanol extract (80ME) and solvent fractions of the leaves of Myrtus communis L. in mice. METHODS: The antidiarrheal activity of the 80ME and solvent fractions was evaluated against castor oil induced diarrheal model, charcoal meal and enteropooling tests. For the 80%ME, the test groups received 100, 200 and 400 mg/kg of the extract. In case of fractions, the test groups received various doses of fractions (200, 300, 400 mg/kg and an additional dose of 800 mg/kg for the aqueous fraction (AF)), where as negative controls received the vehicle (10 ml/kg) and positive controls received loperamide (3 mg/kg). RESULTS: The 80ME at 200 mg/kg (p < 0.05) & 400 mg/kg (p < 0.01) as well as the chloroform fraction (CF) and methanol fraction (MF) at 400 mg/kg (p < 0.05) significantly delayed the onset of diarrhea. Besides, the 80ME (at all tested doses) and both of these fractions (at 300 & 400 mg/kg) significantly decreased the frequency and weight of fecal outputs. Results from the charcoal meal test revealed that the 80ME, at all doses, (p < 0.001) as well as the CF and MF at 300 mg/kg (p < 0.05) & 400 mg/kg (p < 0.001) produced a significant anti-motility effect. Similarly, in the entero-pooling test, the 80ME (at all tested doses) (p < 0.01) as well as the CF and MF (at 300 & 400 mg/kg, p < 0.05) produced a significant decline in the weight and volume of intestinal contents, whereas the AF revealed significant effect (p < 0.05) at dose of 800 mg/kg only. CONCLUSION: The study demonstrated that the 80ME and solvent fractions contain bioactive constituents that have antidiarrheal activity. Therefore, this study provides a scientific support for the acclaimed traditional use of Myrtus communis L for the treatment of diarrheal diseases.