Pharmacology

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A comparative study of the leaf and root extracts of Stephania abyssinica (Dillon & A. Rich) Walp on wound healing activity in mice
(Addis Ababa University, 2023-07) Girma,Minilu; Petros,Zelalem (PhD); Tamirat,Dagnachew(MD)
The roots and leaves of Stephania abyssinica are traditionally used to treat wounds in several regions of Ethiopia. The pharmacological screening for wound-healing activity of the plant was done for the crude extract and solvent fractions of the root extract. But there have been no pharmacological studies done on the wound-healing effect of the leaf extract. In this study, the wound-healing effects of both the 80% methanol extract of the leaves and the roots of S. abyssinica were evaluated using the excision wound model, and the results were compared. Histopathological investigations were also carried out. The antioxidant activity of both the leaf and root extracts was also assessed. In addition, preliminary phytochemical screening tests and quantification of total phenolic, flavonoid, and alkaloid contents were done for both the leaf and root extracts. Both the root and the leaf extracts significantly increased the rate of wound contraction (p < 0.05) and shortened the re-epithelialization period (p < 0.01). The root extract significantly increased the skin‟s tensile strength (p ˂ 0.001). The quantity of secondary metabolites in the root extract, such as total phenolic, flavonoid, and alkaloid contents, was found to be higher than those of the leaf extract, and this concentration difference demonstrated a substantial difference in its wound healing activity.
Activity Testing, Toxicity Assay and Characterization of Chemical Constituents of Medicinal Plants Used to Treat Tuberculosis in Ethiopian Traditional Medicine
(Addis Ababa University, 2016-04) Kahaliw, Wubayehu; Engidawork, Ephrem (PhD); Abebe, Markos (PhD)
Background: Tuberculosis (TB) is the leading killer disease worldwide. In 1993, WHO declared TB as a ‘global emergency,’ which requires emergency action and launched several programs to curb the disease, including the search for newer remedies and/or anti- TB agents to complement currently used agents. Hence, herbal remedies have become the readily available alternatives in the search for new antimycobacterial compounds. Objective: To investigate antimycobacterial activity and toxicity of selected Ethiopian medicinal plants (Otostegia integrifolia, Vernonia amygdalina, Persea americana, Pterolobium stellatum and Carissa edulis) as well as to isolate the main active principles through a bioassay guided process. Methods: Antimycobacterial activity test was conducted using the broth microdilution and microtitre resazurin assay methods in 96 well microtitre plates and MIC was determined by colony counting and resazurin color change observation for all test materials. Cytotoxicity test was performed based on the CellTiter 96® AQueous One Solution Cell Proliferation Assay on HepG2 cells. Genotoxic effects of extracts were evaluated using SCGE method on HepG2 cells. 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, while chloroform extract of V. amygdalina and C. edulis didn’t show significant activity compared to negative controls. The MIC of positive control was 0.125 μg/ml against the standard strain. However, MDR-TB clinical isolates were isoniazid resistant. Fractionation and activity testing of the chloroform extract of P. stellatum revealed that ethyl acetate ii fraction to be the most active fraction against M. tuberculosis H37Rv with MIC of 0.195 μg/ml. The MICs of compound 1, 2 and 3 were 1.25, 2.5 and 0.625 μg/ml, respectively. In the cytotoxicity test, V. amygdalina chloroform extract showed the highest IC50 value (3.202±0.3375), which suggests its safety. O. integrifolia and P. stellatum chloroform extracts were the most toxic in dose dependent manner as one can see the steepness of the dose-response curve. 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 rest of test extracts seemed to be without genotoxic effect up to a concentration of 0.5 mg/ml. Cytotoxicity test was not in the objectives of my study. Conclusion: P. stellatum, O. integrifolia and P. americana have potential to be developed into new anti-TB drugs or standardized herbal medicines. P. stellatum chloroform extract was the most active extract and hence, three compounds were isolated from ethyl acetate fraction and they were active against M. tuberculosis H37Rv. The results have also validated indigenous medical knowledge from the local people regarding the use of these species to treat TB. The IC50 value of P. stellatum chloroform extract was relatively higher compared to other extracts, suggesting its safety. In addition, its selectivity index was 13.5, which demonstrated > 10 selectivity index, considered as being of interest to the pharmaceutical companies. The genotoxicity assay findings revealed that the chloroform and 80% methanol extracts of P. stellatum caused DNA damage at 1 mg/ml and 0.5 mg/ml concentrations. Thus, necessary precautions should be taken during utilization of this plant.
Analgesic and anti-inflammatory activities of Albizia gummifera (J. F. Gmel) C.A. Sm. bark hydro-alcoholic extract and its fractions in rodents
(Addis Ababa University, 2023-10) Tamirat,Mesfin; Petros,Zelalem(PhD); Shibeshi,Workineh(PhD)
Background: The majority of illnesses present as pain and inflammation. Despite advancement in pain medicines, there is a need for safe, effective analgesic drugs. In folkloric medicine, A.gummifera has been used for pain and inflammation, but not scientifically evaluated. Objectives: This study aimed to investigate the analgesic and anti-inflammatory activities of A.gummifera bark crude extract and its fractions in rodents. Methods: The analgesic activity of the A.gummifera was evaluated using an acetic-acid- induced writhing test and hot plate test by using acetyl salicylic acid 150 mg/kg and morphine 10 mg/kg as standard, respectively. Carrageenan-induced paw edema and cotton pellet granuloma methods were used to investigate the anti-inflammatory effect with Indomethacin 10 mg/kg and dexamethasone 0.5 mg/kg as the reference drugs, respectively. Three doses are selected based on the acute toxicity test result: 100 mg/kg, 200 mg/kg, and 400 mg/kg. Results: The A.gummifera bark crude extract and its fractions did not show any sign of toxicity at 2000 mg/kg. The crude extract and its fractions showed statistically significant analgesic and anti-inflammatory activities as compared to the control group (p<0.05). The crude extract and methanol fractions reduced writhes by 66.68% and elongate latency period by 61.47% on 60 and 90 minute, respectively. The maximum edema inhibition was 62.15% in the aqueous fraction after 2 hours of administration. Aqueous fraction produces maximum exudate and granuloma inhibition (62.07% and 65.66%, respectively). Conclusion: This study found that, A.gummifera bark crude extract and its fractions possessed promising analgesic and anti-inflammatory property.
Anti-hyperglycemic activities of hydro-alcoholic, alkaloid and non-alkaloid extracts of Calpurnia aurea (aiton) benth (Fabacea) against streptozocin induced diabetic mice
(Addis Ababa University, 2023-11) Beyene, Habtamu; Engidawork,Ephrem(Prof.); Shibeshi,Workineh(PhD)
Background: Diabetes mellitus is a metabolic disease with several etiologies that is typified by persistently high blood sugar levels. Given the rising rates of diabetes-related morbidity and death in low- and middle-income countries, it is critical to evaluate the potential pharmacological effects of medicinal plants in order to complement current diabetes treatments. The experimental plant Calpurinaaurea(Aiton)Benth is among the Fabaceae species, which is used traditionally for diabetes and other health disorders. Objectives:The purpose of this study was to assess the effects of crude, alkaloid, and non- alkaloid leaf extractsof C.aurea on blood glucose control in streptozotocin-induced diabetic mice and normoglycemic mice. Methods: The crude, alkaloid, and non-alkaloid extracts were prepared using the proper solvents prior to the commencement of the in-vivo investigation. Swiss albino mice, weighing between 20 and 30 grams, were selected for the animal trials. In order to study the hypoglycemic/antihyperglycemic effect of the extract, nine groups of diabetic mice and eleven groups of normal mice were used. Streptozotocin was used to induce diabetes, and blood glucose levels were measured with a glucometer. Doses of the plant alkaloid and non-alkaloid extract (100, 200, and 400 mg/kg) were administered to the test groups in each model while the crude extract was administered at lower doses(50, 100, and 200 mg/kg). Glibenclamide(5 mg/kg) served as a standard drug. The negative control, and the normal control were given 1% of tween 80 (10 mg/kg). Results: The results demonstrated that crude, alkaloid, and non-alkaloid extracts of C.aurea leaves lowered the incidence of hypoglycemia. After the administration of2.5 mg/kg of glucose, the alkaloid extract demonstrated significant lowering of blood glucose levels: 200 mg/kg at 80 minutes (p<0.05) and 400 mg/kg at the first and second hour (p<0.01). All extract-treated groups of streptozotocin induced diabetic mice had decreased blood glucose levels, besides the mice iv administered the alkaloid extract showed a statistically significant drop in blood glucose levels. The alkaloid extract reduced blood glucose levels in the 200 (P<0.05) and 400 mg/kg doses (162±5.21, 142±3.51), respectively, were used in a single dose study. Furthermore, the alkaloid extract at the middle dose (p<0.05), higher dose (p<0.01), and all doses at the third week all significantly decreased the fasting blood glucose level. Furthermore, compared to the negative control group, the groups treated with crude, alkaloid and non-alkaloid extracts experienced a lesser drop in body weight following the onset of diabetes mellitus.Conclusion:it can be concluded that the alkaloid extracts of C.aurea leaves are effective in lowering blood glucose levels in diabetic mice and lack a hypoglycemic effect in normoglycemic mice. Additionally, the extracts were observed to exhibit no acute toxicity.
Anti-ulcer activity of aqueous root extract of Ensete ventricosum (Welw.) Cheesman (Musaceae) in experimental rats
(Addis Abeba University, 2021-07) Hailu, Dejene; Shibeshi, Workineh (PhD); Umer, Shemsu (PhD); Arayaselassie, Mahlet (MD)
Peptic ulcer is a chronic disease of gastrointestinal system caused by an imbalance between damaging factors and protective factors. Even though many antiulcer drugs used to treat this disease are available, most of these drugs produced undesirable side effects, microbial resistance and danger of drug interactions during therapy. An ethnobotanical study showed that Ensete ventricosum is used for treatment of peptic ulcer but the efficacy and safety are not established. Thus, this study was aimed to evaluate the anti-ulcer activity of aqueous root extract of Ensete ventricosum (E. ventricosum) in experimental rats. The effect of the extract on gastric ulcer was evaluated against indomethacin, ethanol and pyloric ligation-induced ulcer models at doses of 100, 200 and 400mg/kg. Dose levels were selected based on outcome of acute toxicity study. Pantoprazole at a dose of 40mg/kg was used as a standard drug while distilled water was used as negative control. In indomethacin and ethanol-induced ulcer, pretreatment with aqueous root extract of E. ventricosum significantly reduced level of gastric mucosal ulceration and improved ulcer protection. Furthermore, histopathological findings of rats pretreated with aqueous root extract of E. ventricosum also revealed gastroprotective activity. In pyloric ligation-induced ulcer, administration of E. ventricosum at a dose of 200 and 400mg/kg significantly (p<0.05) reduced both ulcers number and severity scores and histopathological findings also revealed gastroprotective activity of the extract. The extract at a dose of 400mg/kg exerted best ulcer protection (98.53%) which was comparable to standard drug in pyloric ligation-induced ulcer as compared to other models studied. The extract at a dose of 200 and 400mg/kg also displayed antisecretory activity as revealed by significant (p<0.05, p<0.001) reduction in volume, free and total acidity of gastric juice with significant (p<0.05, p<0.001) increment in pH of the gastric juice in both ethanol and pyloric ligation-induced ulcer in dose dependent manner. In conclusion, the aqueous root extract of E. ventricosum showed significant antiulcer activity.
Antibiotic Use Practice and Predictors of Hospital Outcome Among Patients with Systemic Bacterial Infection at Tikur Anbessa Specialized Hospital: Identifying Targets for Antibiotic and Health Care Resource Stewardship
(Addis Ababa University, 2015-04) Alemkere, Getachew; Tenna, Admasu(PhD)
Background: Despite massively used in different settings, about half of antimicrobial agents prescribed to hospital in-patients were considered inappropriate. Such malpractice and excess use has been associated with increased mortality, adverse drug reactions, financial cost and the development of resistant bacteria, which have become a threat for the generation. These calls for an integrated intervention that should better are preceded with identification of targets. Objective: To assess the antibiotic use practice and to identify predictors of hospital outcome among patients with systemic bacterial infection to uncover targets for antibiotic and health care resource stewardship Methods: A prospective cross-sectional study was performed from 9 April to 7 July in the internal medicine wards of Tikur Anbessa specialized Hospital. Patients who had and/or developed systemic bacterial infections during this period were strictly followed. Data abstraction format was used to collect data on demographic, disease, drug and microbiologic related factors. Pattern of antibiotic use was assessed and predictors for mortality and length of stay (LoS) were identified. Descriptive statistics and Binary logistic regression were used for statistical analysis. Results: Females accounted for about 52% of the 323 study participants whose mean age was 41.8. Of all, 75.2% of the participants had suspected infection during ward admission. Cephalosporins were the most widely prescribed class of drugs in the internal medicine wards and the medical ICU. Based on changes to microbiologic culture reports the initial antibiotic uses were inappropriate in all of the ICU and 99.3% of the ward patients. About 28% of the wards and 59% of the ICU patients were died during the in-hospital stay. The mean (+ SD) LoS was 18.5+12.2 in the wards and 8.9+4.9 days in the ICU. Whilst presence of HIV, liver-cirrhosis, different signs and symptoms of disease, neoplasm, sepsis, meningitis, renal failure, vancomycin and increased antibiotic courses (> 2) were iv positive predictors, prolonged antibiotic days (>10) and simultaneous antibiotic uses (>3) were negative predictors of mortality. On the other hand, age range of 25-44, hospital acquired infection and prolonged agent days (>21) (positively) and on admission infection (negatively) were independently associated with prolonged LoS. Conclusion: Generally, these observations call for the establishment and implementation of antimicrobial stewardship that facilitate appropriate use of antimicrobials as a whole in the context of resource limited settings. Any stewardship activity should better start by addressing infections like pulmonary, sepsis and meningitis and drugs like vancomycin. Key words: Antimicrobial Stewardship, Antibiotic use, Length of Stay, In-hospital Mortality, Tikure Anbesa Specialized Hospital, Ethiopia
Anticonvulsant Effect of Pterlobium stellatum (Leaves), Moringa stenopetala (Root) And Clutia abyssinica (Leaves) Traditionally Used for Treatment of Epilepsy in Ethiopia Using Mice Model
(Addis Ababa University, 2021-06) Sahile Salile, Samson (PhD); Prof. Abula, Teferra
Background :Epilepsy is the third leading contributor to the global burden of disease for neurological disorders and affects 65 million people worldwide. Although the current antiepileptic drugs achieve symptomatic seizure relief they do not prevent or reverse the pathological process that underlies human epilepsy. Drug resistant epilepsy is also one of the most important unmet needs in the daily management of epilepsy. These currently unmet needs provide a roadmap for the development of more effective antiseizure drugs, as well as for disease modifying and antiepileptogenic drugs especially from plants. This study was conducted to investigate the anticonvulsant activity of the crude hydroalcoholic extracts of 3selected plants Pterlobium stellatum ( leaves), Moringa stenopetala (root) and Clutia abyssinica (leaves). These all are used for treatment of epilepsy by traditional healers in different parts of Ethiopia. Additionally the solvent fractions of the Pterlobium stellatum were tested for anticonvulsant activity as the crude extract showed positive response in all the models used. Methods :.The dry residues of the plant extracts were used for test in different doses. Male balb c mice were used for in vivo study and for in vitro study P14-P21 of C57BL16 mice were used. In vitro mice model of hippocampal slice with 0Mg 2+ was used and the extracts were tested at the 0.7mg/kg concentration. Diazepam 3µM was positive control and DMSO as negative control. In in vivo PTZ and MES mice models 400mg/kg and 800mg/kg of each test extract were used for efficacy test in as positive control Diazepam 5mg/kg and phenytoin 10mg/kg were used respectively. The negative control was 2% tween 80 .Fisher's exact test was used to analyze proportions and ANOVA with post hoc LSD to test means. The tests were conducted after the ethical clearance was obtained from the ethical committee of Addis Ababa University and university of Cape Town. Qualitative test and quantitative tests were used to determine the secondary metabolites in the plants. And ultraperformance liquid chromatography-mass spectrometer (UPLCMS) tests were used to characterize plant constituents in Pterlobium stellatum crude extract and its fractions. Results :In the in vitro study the hydroalcoholic extract of P.stellatumand M. stenopetalaat 0.7mg/ml had a statistically significant anticonvulsant activity compared to negative control(P<0.05). The hydroalcoholic extract of C.abyssinicaat 0.7mg/ml didn't show statistically significant effect compared to negative control (P>0.05). A positive control, diazepam(3µM), showed statistically significant anticonvulsant activity compared with negative control (P<0.05).When we compare the in vitro activity of different solvent fractions of P. stellatum,the chloroform and water fractions at 0.7mg/ml were also shown to have significant anticonvulsant activity as compared to negative control (P<0.05). The petether and butanol fractions activities were not statistically significant compared to negative control (P>0.05). Pterolobium stellatum hydroalcoholic extract shown that dose dependent and statistically significant anticonvulsant activity with PTZ model(P<0.05).Whereas the activity of M. stenopetala and C. abyssinica hydroalcoholic extracts were not statistically significant (P>0.05) in in vivo PTZ model. The in vivo PTZ test has also revealed the chloroform fraction and the water fraction of Pterolobium stellatum to have anticonvulsant effect(P<0.05) compared with the negative control. Whereas the pet ether and butanol fractions shown activity which was not statistically significant with negative control(P>0.05).The effect of the diazepam was statistically significant with the negative control and all test extracts (P<0.05). Pterolobium stellatum and M. stenopetala hydroalcoholic extracts shown statistically significant anticonvulsant activity with MES model in both lower and higher doses(P<0.05). The C. abyssinica hydroalcoholic extracts activity at the given doses were not statistically significant (P>0.05).The in vivo MES test has also revealed the chloroform fraction to have anticonvulsant effect at both doses (P<0.05). The water fraction at 400mg/kg dose shown anticonvulsant effect compared with the negative control(P<0.05). The pet ether and butanol fractions shown activity which was not statistically significant at the given doses (P>0.05).The effect of the phenytoin was statistically significant with the negative control as well as compared with other tested extract doses(P<0.05). The qualitative and quantitative analysis indicated the presence of different plant secondary metabolites in hydromethanolic extracts of the three plants. In Pterolobium stellatum the UPLCMS analysis indicated also the presence of gallic acid, ellagic acid, kaempferol, myricitrin, isoquercitrin and quercitirin in the crude extract. Of these gallic acid and ellagic acid were found in chloroform fraction. In the water fraction ellagic acid, kaempferol, myricitrin and isoquercitrin were found. Conclusion: The results demonstrated that Pterolobium stellatum has anticonvulsant effect. The hydroalcoholic and chloroform and water fraction of Pterolobium stellatum demonstrated effect in both in vitro and in vivo MES and PTZ models of epilepsy. The crude extract of Moringa stenopetala has also shown to have anticonvulsant effect both in the in vitro and in vivo MES models. But was negative on PTZ model. The traditional use of both herbs for treatment of epilepsy can be supported by the finding of this study. However ,C. abyssinica didn't show anticonvulsant activity at the tested doses in the models used in this study and its traditional use for treatment of epilepsy is not supported according to the findings of this study.
Anticonvulsant Activity of 80% Methanol Extract and Solvent Fractions of Ajuga integrifolia Buch.-Ham (Lamiaceae) leaves in Mice
(Addis Abeba University, 2020-11) Getaneh, Yigrem; Abula, Teferra( Professor)
Ajuga integrifolia is one of the species in the genus Ajuga that is used in the Ethiopian traditional medicine for the treatment of different ailments, including epilepsy. Thus, this study was initiated to evaluate the traditional anticonvulsant use of 80% methanol leaves extract and solvent fractions of Ajuga integrifolia. Acute routine screening tests; the pentylenetetrazole (PTZ) and maximal electroshock (MES) models were used. The rota rod test was further performed to evaluate neurotoxic effect of the plant. Swiss albino mice of 6-8 weeks old were randomly assigned to five groups (n=6/group). The test groups received 100, 200 and 400mg/kg oral dose of crude extract and solvent fractions for both PTZ and MES tests as well as 2.5, 5 and 10mg/kg i.p. dose for rota rod test. The positive control groups received valproate 200mg/kg oral for PTZ, phenytoin 25mg/kg oral for MES, and diazepam 5mg/kg i.p for rota rod test. The negative control groups received oral dose of 10 ml/kg of distilled water or 2% tween 80. The crude extract produced dose dependent and statistically significant anticonvulsant effect on both PTZ and MES induced seizures. It was suggested by delayed latency (p<0.001 for 400 mg/kg and p<0.05 for 100mg/kg and 200mg/kg) and fast recovery (p<0.001 for all doses) on PTZ and reduction of duration of tonic hind limb extension (p<0.001 for all doses) in MES model, against control. Similarly, n-butanol and chloroform fractions displayed dose dependent activity in both models as evidenced by having significant activity against control. However, aqueous fraction at doses used did not show a significant effect on latency and duration on both models. Furthermore, all doses of the crude extract and solvent fractions did not display a significant change in motor coordination. The plant extract contained alkaloid, glycosides, flavonoids, phenols, steroids, tannins, terpenoids and saponins that might contribute to the observed anticonvulsant activity. In conclusion, the plant has anticonvulsant activity at various doses providing evidence for its traditional use.
Anticonvulsant Activity of Soxhlet Leaf Extracts of Ajuga Integrifolia Buch.Ham ex D.Don (Lamiaceae) in Mice
(Addis Ababa University, 2021-11) Desalegn, Tesfaye; Prof. Engidawork, Ephrem
Epilepsy is one of the most common chronic neurological conditions that affect 70 million people in different parts of the world. The leaves of Ajuga integrifolia Buch.ham ex D Don have been used as anti-convulsant remedy in Ethiopian traditional medicine. However, the evidence supporting this claim 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. To this effect successive Soxhlet extraction was performed using n-hexane, ethyl acetate, methanol and water. Anti-convulsant activity of the extracts was investigated in both acute (pentylenetetrazole, PTZ; and maximal electroshock, MES) and chronic (PTZ kindling) seizure models. For the acute model, various doses of the extract (100mg/kg, 200mg/kg and 400mg/kg) were administered. Positive controls received sodium valproate (200mg/kg) for PTZ and phenytoin (25mg/kg) for MES. Distilled water or 2% tween 80 was used for negative controls. Kindling was induced by repeated alternate day intra-peritoneal administration of sub-convulsive dose of PTZ (35 mg/kg) for 13 days and the most active extract (ethyl acetate) was tested in this model. Parameters including onset of clonus and duration of hind limb tonic extension were recorded. Moreover, total alkaloid, flavonoid and phenol contents of the most active extract were determined. Treatment of mice with ethyl acetate extract produced a superior effect among all solvent extracts in both PTZ and MES model. The mean latency to clonic seizure was significantly increased (p<0.01) with all doses of ethyl acetate extract in PTZ test compared to control and n.hexane extract ranked next to ethyl acetate extract in increasing onset of clonus. It significantly increased mean onset of clonus compared to controls, with a maximum increase (12.67min, p<0.001) displayed by HA400 mg/kg. Methanol extract at 200mg/kg and 400 mg/kg also significantly delayed onset of clonus (p<0.001) in PTZ model.Once again, all doses of ethyl acetate extract of the study plant significantly reduced (p<0.001) the mean duration of hind limb tonic extension in MES test compared to control. Hexane extract at 200 mg/kg and 400 mg/kg also significantly reduced (p<0.001) duration of hind limb tonic extension. Methanol extract at 200mg/kg and 400 mg/kg also significantly reduced (p<0.01) mean duration of hind limb tonic extension (HLTE) compared to control in MES test. Aqueous extract at all doses was devoid of any anti-convulsant effect in both models. A similar type of study done on the leaf crude extract and solvent fractions collected from different geographical location also reported anti-convulsant activity of the plant in acute seizure models. Treatment of mice with 200mg/kg and 400mg/kg of ethyl acetate extract along with alternate day PTZ injection significantly protected(p<0.01 for 200mg/kg and p<0.001 for 400 mg/kg) against PTZ induced kindling compared to controls in chronic model. Ethyl acetate extract of the plant 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 /g of dry weight extract of flavonoids and 21.928 ±1.118 mg gallic acid equivalent / g of dry weight of extract of phenols. This study indicated that the plant has anti-convulsant activity in both acute and chronic model and it could be a potential source to develop a new anti epileptic drug for pharmacoresistant epilepsy.
Antidepressant-like Activity of Solvent Fractions of the Root Bark of Carissa spinarum Linn. (Apocynaceae) in Rodents
(Addis Ababa University, 2022-03) Saif, Hana; Prof. Engidawork, Ephrem
Depression is a chronic and recurrent psychiatric disorder affecting mental and physical health. Traditional medicines have been used for decades in the treatment of depression due to resistance development, side effects, inadequate accessibility and affordability of modern antidepressant drugs. The root bark of Carissa spinarum Linn. (Apocynaceae), which is used traditionally for depression is reported to possess antidepressant- like activit y in rodent models of depression. In the current study, different fractions of the root bark obtained using solvents of different polarities were investigated using a host of models, including tail suspension test (TST), forced swim test (FST), muricidal behavioral test, and open field test (OFT). Moreover, markers for depression and phytoconstituents were determined, and preliminary mechanistic studies using different drugs were also conducted. Five groups of animals of either sex each having 6 animals per group were randomly assigned for every model and each solvent fraction (Ethyl acetate, n-butanol, and aqueous). Group I, served as a negative control group and received a vehicle (2% Tween 80), group II served as a positive control and received the standard drug Imipramine (30 mg/kg), group III-V received increasing doses of the solvent fractions 50, 100 and 200 mg/kg, respectively. Ethyl acetate (CSE) and n-butanol (CSB) fractions significantly (p<0.001) reduced the duration of immobility in TST and FST, while the aqueous fraction (CSA) failed to show any appreciable antidepressant- like activity. No change in the locomotor activity using OFT was observed at all doses. From the two active fractions, the ethyl acetate fraction was the most effective and contributed to reducing the muricidal behavior in rats. Serum corticosterone level was reduced by both fractions and once again the ethyl acetate fraction was the most effective. Mechanistic studies revealed the involvement of multiple neurotransmission systems, including adrenergic, dopaminergic and choline r gic as well as the L-Arginine-NO-cGMP pathway in the antidepressant- like effect of the plant, hence only both the dopaminergic and the L-Arginine-NO-cGMP pathway were the predominant by which the ethyl acetate fraction might mediate its action. Phytochemica l analysis showed the presence of high content of alkaloids (0.17 mgATE/g and 0.07 mgATE/g), flavonoids (12.43 mgQE/g and 2.07 mgQE/g), and phenols (42.42 mgGAE/g and 29.8 mgGAE/g) for CSE and CSB, respectively. The findings collectively indicate that CSE and CSB are endowed with antidepressant- like activity due to the presence of phenols, flavonoids, and alkaloids, which are medium polar in nature.
Antidiarrheal Activity of Aqueous and 80% Methanol Extracts of the Leaves of Leucas Abyssinica (Lamiaceae) in Mice
(Addis Abeba University, 2020-11) Abera, Tadele; Abula, Teferra( Professor)
Leucas abyssinica (Lamiaceae family) is one of the medicinal plants used for the management of diarrhea in Ethiopia but it lacks scientific evidence. Thus, this study was aimed to evaluate the antidiarrheal activities of aqueous and 80% methanol extracts of the leaves of Leucas abyssinica using experimental models in mice. castor oil induced diarrhea, misoprostol induced enteropooling, normal and castor oil induced gastrointestinal transit in mice models were used to evaluate antidiarrheal activity of the plant. Five groups of mice (six animals per group) were used for each model. These groups were negative control group (received distilled water 10 ml/kg), positive control group (administered loperamide 3 mg/kg) and three test groups (treated with graded dose of 100, 200 and 400 mg/kg aqueous and methanol 80% extracts respectively). Pretreatment of mice with stated doses of both extracts of the plant significantly reduced the frequency of wet and total feces, the weight of wet and total feces as well as increased diarrheal free periods compared to negative controls. Both extracts produced significant reduction in both the weight and volume of intestinal contents induced by misoprostol in a dose dependent manner. The percentage of inhibition of gastrointestinal transit induced by castor oil for both extracts were significant (p < 0.001) at all the tested doses in a dose dependent fashion. But none of the tested doses of both extracts significantly reduced normal gastrointestinal transit in mice. Finally, the results from this study suggests that both extracts of the plant have significant antidiarrheal effect on animal models and this finding supports the antidiarrheal traditional use of the plant for management of diarrhea.
Antimalarial Activity of 80% Methanol Extract of The Stem Bark of Syzygium Guineense (Willd.) DC. (Myrtaceae) In Mice Infected with Plasmodium Berghei
(Addis Ababa University, 2015-03) Zeleke, Gemechu; Engidawork, Ephrem (PhD); Shibeshi, Workineh(PhD); Teklehaymanot, Tilahun(PhD)
Malaria is one of the world’s most deadly infectious diseases. Spread and emergence of antimalarial drug resistance is the major challenge that endangers all the recent gains in malaria control. Medicinal plants are the key source of new effective antimalarials. Syzygium guineense is commonly used by traditional healers’ in many parts of Africa including Ethiopia for treatment of malaria. Thus, this study attempted to evaluate in vivo antimalarial activity of 80% methanol extract of the stem bark of the plant in mice infected with Plasmodium berghei ANKA strain. To this effect various doses (100, 200, 400 mg/kg) of the extract were evaluated for the antimalarial effect using the four-day suppressive, curative and prophylactic tests. Parameters, including percent parasitemia, survival time, body weight, body temperature and packed cell volume (PCV) were determined using standard procedures. A significant (p<0.001) parasite suppression of 11.20%, 34.04% and 45.05% was observed with 100, 200, and 400mg/kg of the extract, respectively, in early infection. On the other hand, a significant parasite suppression was observed by the extract in curative test with 400 mg/kg (36.3%, p<0.001) being the highest. In the prophylactic test, 100, 200, and 400mg/kg of the extract produced 26.91%, 37.13%, 58.24% parasite suppression, respectively. In addition, the standard produced significant parasitemia suppression in all tests. In general, the extract of stem bark of S. guineense showed considerable in vivo antimalarial properties with outstanding prophylactic activity. The phytochemical screening of the extract showed the presence of alkaloids, anthraquinones, terpenoids, saponins, tannins, phenols and flavonoids. The findings suggest that S. guineense contain active phytochemicals that could potentially be a lead compound in the search for new antimalarials. Key words: Syzygium guineense, Plasmodium berghei, Antimalarial activity
Antimalarial Activity of Aqueous and 80% Methanol Crude Seed Extracts and Solvent Fractions of Schinus molle Linnaeus (Anacardiaceae) in Plasmodium berghei Infected Mice
(Addis Ababa Universty, 2018-11) Habte, Getu; Nedi, Teshome (PhD)
Antimalarial activity of aqueous and 80% methanol crude seed extracts and solvent fractions of Schinus molle Linnaeus (Anacardiaceae) in Plasmodium berghei infected mice Getu Habte Addis Ababa University, 2018 Malaria is one of the major global public health problems. Resistance to antimalarial drugs has been a major challenge in controlling the disease. This issue makes the development of novel antimalarial drugs a necessity. Medicinal plants had been one of the important sources in discovering antimalarial drugs. Schinus molle Linnaeus is among medicinal plants that are used for the treatment of malaria in Ethiopia and exhibited in vitro antimalarial activity. Nevertheless, it lacks further in vivo pharmacological investigations to substantiate its antimalarial activity. As a result, this study was aimed at investigating in vivo antimalarial activity of aqueous and 80% methanol crude seed extracts and solvent fractions of Schinus molle in Plasmodium berghei infected mice using peter’s four day suppressive test. The crude extracts and fractions were administered at doses of 100, 200 and 400mg/kg. Parameters including body weight, packed cell volume, temperature, survival time and parasitemia were then determined. The crude extracts and solvent fractions exerted significant inhibition of parasitemia compared to the negative control. Chemosuppressive effects exerted by the crude extracts and solvent fractions were in a range of 27.18-66.91% and 15.64-55.60%, respectively. The highest inhibition of parasitemia was exhibited by the highest dose of 80% methanol crude extract. Among the fractions of the 80% methanol crude extract tested, chloroform fraction demonstrated the highest inhibition. Moreover, the crude extracts and solvent fractions prevented loss of weight, reduction in temperature and anemia compared to the negative control in a dose dependent manner. In addition, they significantly prolonged the survival time of infected mice except the aqueous fraction. In conclusion, the findings of the present study show that the seed of Schinus molle has in vivo antimalarial activity which supports the traditional claim and promising to be a source for developing more effective and safer antimalarial drugs, and alerts in depth investigations on the plant.
Antimicrobial Resistance Pattern of Common Bacterial isolates in Soddo Christian Hospital
(Addis Ababa University, 2017-01) Worku, Yalemzerf; Nedi, Teshome (PhD)
Infectious diseases are the leading causes of mortality and morbidity in developing countries. Management of infectious disease requires potent and effective antimicrobial drugs to which the virulent organisms are susceptible.. A retrospective cross-sectional study was done by reviewing 1500 microbiology records from September, 2009 to August, 2014. From 1500 microbiology records, 1086 bacteria were isolated. Among these (4.9%) were mixed infection . The most common isolated bacteria were S. aureus and P. aeruginosa with an isolation rate of (17.3) and (14.3%) respectively. About 47.4 % of S.aureus was oxacillin/methicillinresistant (MRSA).Ontheother hand, the resistance rate of S. aureus was lower to ceftriaxone 172 (19.8%). S. pyogenes was resistant to tetracycline while lower resistance was observed to erythromycin,. The highest resistance rate of P. aeruginosa and E. coli were found to ampicillin and amoxicillin. From multidrug resistant bacteria, majority were gram negative among which P. aeruginosa (97.7%) was the highest followed by E. coli (95.1%). Among gram positive MDR bacteria S.aureus (89.1%) was the highest followed by S. epidermidis (87.5%). The findings of this study show that there is high resistance rate of bacterial isolates to the commonly used antimicrobials. To benefit maximum antimicrobial effect from the active antimicrobials and to reserve the threatened ones rational use of antimicrobials should be practiced. Key Words: Antimicrobial Resistance, Antibiotic Susceptibility, Bacterial Isolates.
Antimicrobial susceptibility pattern of bacterial uropathogens and associated factors of urinary tract infection among pregnant women attending antenatal care clinic of hiwot Fana specialized university hospital, Harar, Eastern Ethiopia
(Addis Ababa Universty, 2018-06) Workneh, Alemseged; ababula, Teferra(Professor)
Antimicrobial susceptibility pattern of bacterial uropathogens and associated factors of urinary tract infection among pregnant women attending antenatal care clinic of hiwot Fana specialized university hospital, Harar, Eastern Ethiopia Alemseged Workneh Addis Ababa University,2018 Urinary tract infections(UTI) are the commonest bacterial infections during pregnancy, leading to significant maternal and prenatal mortality.Moreover, the changing pattern of antimicrobial susceptibility of bacterial uropathogens is another growing problem. Therefore, this study was aimed to determine bacterial uropathogens is another growing problem.Therefore, this study was aimed to determine bacterial uropathogens, their antimicrobial susceptibility pattern and associated risk factors of UTI anong pregnant women attending at ANC clinic of Hiwot Fana Specialized university Hospital, Harar, Eastern Ethiopia. Hospital based cross-sectional study was conducted from November, 2017-January,2018 on 200 conveniently selected pregnant. data collection involved face to face interview, urine culture,and antimicrobial susceptibility test. Statistical models such as bivariate and multivariate logistic regression were used to analyze the date. The overall prevalence of UTI was 15.5%. A total of 31 bacterial uropathogens were isolated. E.coli 45.2% was the most isolated Gram negative bacterial pathogen followed by proteus spp, 22.6% and K.Pneumoniae, 16.1%. Most of the isolated bacteria showed high level of sensitivity to amikachin 96.4%, nitrofurantoin, 90.3% and gentamicin, 83.9%. In contrast, resistance of 58.1% to ampicillin, 51.6% to each of augmentin and cotrimoxazole was obtained. Prior use of indwelling catheter(AOR:5.348, 95% CI: 0.984, 29.075), and having previous history of UTI(AOR: 5.624, 95% CI: 2.385,13.261). Were statistically associated with the occurrence of UTI among pregnant women. In general, the early identification of bacterial uropathogens and its antimicrobial susceptibility pattern will help in patient betterment and containment of the spread of resistant bacteria in this study area. As result the clinicians need to prescribe Antimicrobial agent after culture result and hospital should establish well equippe bacteriology laboratory for culture and antimicrobial susceptibility tests.
Antitrypanosomal Activity Of Hydromethanol Extract Of Leaves Of Cymbopogon Citratus And Seeds Of Lepidium Sativum In-Vivo Mice Model
(Addis Abeba University, 2021-07) Yetayeh, Ayechew; Prof.Mekonnen, Eyasu(PhD, Professor of Pharmacology); Beyene, Takele(Associate Professor of Pharmacology)
Trypanosomiasis is one of the neglected tropical diseases of both humans and animals caused by the protozoa Trypanosomes mainly endemic in Africa. Unavailability of vaccine, difficulty of vector controls, low therapeutic index of the available trypanocidal drugs, and development of resistance lead to the need for research focused on developing alternative safer, more effective and more accessible treatment options especialy from medicinal plants. In Ethiopia, many medicinal plants such as Cymbopogon citratus and Lepidium sativum are used for treatment of trypanosomiasis as traditional remedies. The objective of the present study was, therefore, to investigate antitrypanosomal activities of leaves of C. citratus and seeds of L. sativum in in vivo mice model. The acute toxicity result showed that the extracts were safe at the dose of 2000mg/kg, and the test doses were adjusted to 100, 200 and 400mg/kg based on the toxicity profile. The Plants extracts were administered to the respective groups of mice after the 12 th days of T. congolense inoculation where the peak parasitemia were achieved. The treatment continues consecutively up to seven days and the parameters were recorded every other day up to the 14 th day of treatment commenced. The in vivo test results revealed that both plant extracts had dose dependent antitrypanosomal activity. Both crude extracts showed a significant reduction in parasite load (P<0.05), ameliorated anaemia (increased or prevent the fall of PCV value) (P<0.05), decreased lymphocytosis and increased neutrophil counts (p<0.05) and improved body weight but significant body weight increment (P<0.05) was observed only in C. citratus treated mice compared to the negative and positive controls. Comparative results from all tested parameters showed that the best activities were observed with C. citratus treated groups of mice (73.2% reduction).
Antitrypanosomal Activity of Selected Medicinal Plants against Trypanosoma congolense Field Isolate
(Addis Ababa University, 2023-11) Dereje,Beza; Abay,Solomon Mequanente(PhD)
Trypanosomiasis is among the most common neglected tropical diseases (NTDs) of humans and animals. It mainly affects countries with poor health infrastructures and the actual disease burden is unknown. It is estimated that 10 to 14 million heads of cattle, goats and a million equines are at risk of contracting the disease in Ethiopia. Trypanocidal drugs are currently facing a number of problems like toxicity, resistance and availability issues. These limitations have prompted the search for new, safe and effective drugs. In Ethiopia, the seed of Brucea antidysentrica, the leaf of Clematis hirsuta and the root of Rumex nepalensis are used to treat animal trypanosome infection by traditional healers. The study aimed to investigate the in vitro activity of selected medicinal plants against Trypanosoma congolense and in vivo antitrypanosomal activity of the most active plant. The plants were extracted by 80% methanol maceration and tested for their in vitro activity using motility test (at concentration of 4, 2, 0.4 and 0.1 mg/ml) for cessation or reduction in motility of trypanosomes followed by monitoring for loss of infectivity of mice. After 12 days of T. congolense field isolate inoculation of mice and peak parasitaemia level (~108 trypanosomes/ml) was reached, 80% methanol extract of roots of Rumex nepalensis was administered at doses of 100, 200 and 400mg/kg orally once daily for 7 days. ii The packed cell volume, body weight, parasitaemia level and rectal temperature were used as parameters for monitoring in vivo activity by comparing with the positive control: 28 mg/kg dose of diminazene aceturate and negative control: 1% Dimethyl Sulfoxide (DMSO) treated groups. The statistical significance was determined by one-way ANOVA followed by Tukey post hoc test. The motility of T. congolense was ceased by R. nepalensis, B. antidysentrica, and C. hirsuta at concentration of 4mg/ml within 10, 25 and 35min, respectively. Mice treated with 4mg/ml of R. nepalensis and Diminazene aceturate caused loss of infectivity of trypanosomes in mice for 21 days after the inoculation of the in vitro mixtures. The 80% methanol extract of roots of Rumex nepalensis at dose of 2000 mg/kg did not show acute toxicity signs and symptoms. Highly significant (p<0.001) reduction in pre-treatment parasitaemia from (7.30±0.06) to (2.70±1.21) trypanosomes/ml on day 8 of treatment and increased PCV from (45.83±0.31) to (48.00±0.26) and body weight increased from (22.63±0.55) to (26.60±1.14) gram at day 14 was recorded in mice treated with 80% methanol extract of roots of R. nepalensis at the dose of 400 mg/kg. The results revealed that the selected medicinal plants showed antitrypanosomal activity that supports their traditional claim and prompted further studies on isolated active substances from these plants.
Assessment of Adherence and Treatment Outcome among Epileptic Patients on Follow-up at Amanuel Specialized Mental Hospital
(Addis Ababa University, 2015-02) Gedamu, Melak; Engidawork, Ephrem (PhD)
Anti-epileptic drugs (AEDs) are the primary therapeutic modes for epileptic patients and have been demonstrated to control seizure, which decreases morbidity and mortality associated with epilepsy. There is a paucity of data on treatment outcome among 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. Patients who had follow up for at least two years were recruited in the study to evaluate adherence and treatment outcome through medical records review and patient interview. Factors affecting adherence and seizure control were determined using regression analysis. From a total of 397 patients 61% were males. The common type of seizure diagnosed was generalized tonic clonic seizure (76.1%). Monotherapy was commonly (74.8%) used in the management of seizure, among which phenobarbitone was the most commonly utilized (60.5%) single anticonvulsant drug. About 70% patients were adherent to their treatment and 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, for those patients who were seizures free for at least two years, there must be a consideration of clinical assessment to withdraw AED treatment. Key words: adherence, anti-epileptic drugs, epilepsy, treatment outcome
Assessment of Adherence to Ocular Hypotensive Agents among Glaucoma Patients in Menelik II Referral Hospital, Addis Ababa, Ethiopia
(Addis Ababa University, 2015-11) Mehari, Tesfay; Shibeshi, Workineh(PhD); T. Giorgis, Abeba(Assistant Professor)
Without good adherence and appropriate administration technique of hypotensive agents, an elevated intraocular pressure leads to progressive optic nerve degeneration and visual field deterioration. Investigations of adherence and administration technique are very crucial in glaucoma management. The purpose of this study was to assess adherence to ocular hypotensive agents among glaucoma patients in Menelik II Referral Hospital. A hospital-based prospective cross sectional study was conducted on359 patients. Eligible patients were interviewed and their medical charts were reviewed form June 1, 2015 to July 31, 2015 using a pretested structured questionnaire. The rates of adherence and appropriate administration technique were 42.6% and 17.3% respectively. Higher educational level, being self-employed and taking lesser frequency of pilocarpine were significantly associated with adherence while being a farmer, having very low monthly family income and self-purchasing of medications were significantly but inversely associated with adherence. Being a female, having advanced glaucoma and more frequent follow-uphad an important role in deciding appropriate administration technique. In contrary, patients with primary angle closure and open angle glaucoma, who had immediately administered their consecutive dose, had experienced side effect, and had low vision were significantly associated with inappropriate administration technique. Moreover, the odds of being adherent for patients who appropriately administered their medications were almost three-fold greater compared to those who did not administer adequately. In conclusion, both adherence and administration technique were sub-optimal and poor and tailored educational interventions according to the modifiable patient’s and clinical characteristics are required. Key Words: Adherence, Administration Technique, Ocular Hypotensive Agents, Glaucoma
Assessment of Antibiotics Use as surgical Prophylaxis and Post-Operative Treatment at Saint Paul’s Hospital Millennium Medical College
(Addis Ababa Universty, 2018-12) Alamrew, Kerebih; Shibeshi, Workineh (PhD, Associate Professor)
Assessment of Antibiotics Use as surgical Prophylaxis and Post-Operative Treatment at Saint Paul’s Hospital Millennium Medical College (SPHMMC). Kerebih Alamrew Addis Ababa University, 2018 Surgical site infectionsare the most common types hospital acquired infections. Use of antibiotic, when sound and in the appropriate principle of prophylaxis can result in reduced postoperative infections and mortality. The main objective this work was to assess antibiotics use for prophylaxis and post-operative Treatment of surgical patients in surgical wards of SPHMMC. prospective cross-sectional study was conducted by reviewing records of 413 patients who admitted at the surgery wards of SPHMMC between June 10 and September 10, 2016. Descriptive statistics and binary logistic regression were used for statistical analysis. Of the 413 patients studied,231(55.9%) weremales withmean age of patients 38.1±15.1years (range 13 to 82 years). Most surgical patients 187(54.8%) were given Ceftriaxone as prophylaxis and treatment. Among those who received antimicrobial prophylaxis the time of administration was not recorded in 22 (9%) of the patient.Selection was the most deviated parameter from surgical antibiotic prophylaxis 205(91.5%) followed by duration 99(44.2%), and indication 22(5.3%).Surgical site infection rate was 11.1%. Type of admission (p=0.003) and status surgical antibiotic prophylaxis of use(p=0.045) at p< 0.05 (95% confidence interval) were the risk factors associated with surgical site infection. among patients undergoing surgical procedure at the hospital during the study period. In conclusion the study indicates that ceftriaxone was the most used antibiotics. Use of broader spectrum antibiotics for extended period was common.Areas of non-concordance to the guideline require further investigation.

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