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Item Analgesic and Antinflammatory Activities of the Root extract of Grewia schweinfurthii and its Constituent and Determination of Nutritional and Antinutritional Compositions of its Fruit(Addis Ababa University, 2023) Leta,Abdi; Hymete, Ariaya (PhD); Tadesse,Solomon(PhD); Giday,Mirutse(PhD)The utilization of current treatments can often result in harmful side effects, and cause patients to experience pain and inflammation. In Ethiopian, traditional healers have relied on medicinal herbs, such as Grewia schweinfurthii, which possess analgesic and anti-inflammatory properties. Despite their widespread use, studies regarding the nutritional content of wild edible plants (WEPs) in low-income nations like Ethiopia are limited. This study aimed to evaluate the analgesic and anti-inflammatory effects of 80% methanolic root extract of G. schweinfurthii and its chemical constituents, as well as to examining the nutritional and antinutritional content of its fruit. The root extract of G. schweinfurthii and its constituents were evaluated for their analgesic activity using acetic acid-induced writhing and hot plate tests. The root extract was subjected to column chromatography (silica gel) to isolate a compound coded as AL-03 and tentatively identified as 4-(2''-(4'-isopropylphenyl) propan-2''-yl)-2,3-dihydrofuran based on spectroscopic (1H, 13C NMR & HSQC) data. The root extract G. schweinfurthii demonstrated significant analgesic activity (p < 0.001) in the acetic acid-induced writhing test at doses of 200 and 400 mg/kg. Additionally, in the hot plate method, a dose of 400 mg/kg of root extract showed noteworthy analgesic activity (p < 0.001). In the carrageenan-induced acute inflammation model, all doses (100, 200, 400 mg/kg) of the root extract resulted in a significant decrease in paw edema compared to the negative control. Compound AL-03 also exhibited antinflammatory activities in a dose-dependent manner against carrageenan-induced paw edema. XI Proximate analysis was used to assess various nutritional parameters of G. schweinfurthii fruit, including crude protein, fat, total ash, crude fiber, and carbohydrates. In this regard, G. schweinfurthii fruit revealed the following composition: moisture (4.09 ± 0.10%); crude protein (11.24 ± 0.68%); fat (1.99 ± 0.01%); total ash (5.36 ± 0.20%); crude fiber (32.50 ± 0.50%); carbohydrate (44.82 ± 0.82%); and total energy (242.12 ± 1.72 kcal). Furthermore, phytate (62.97 ± 0.83%), tannin (3.97 ± 0.12%), and oxalate (0.28 ± 0.03%) were identified as antinutritional components. Overall, G. schweinfurthii fruit was found to be a reliable source of nutrients and bioactive compounds. The findings support the traditional medicinal use of the plant for analgesic and antinflammatory activities. Further research is recommended to explore additional bioactive compounds from the root extract of G. schweinfurthii and to analyze the mineral composition, such as amino acids, and vitamin C content of G. schweinfurthii fruit, as well as to conduct sub-acute and chronic toxicology testingItem Anthelmintic Activity of the Seed Oil of Ricinus communis(Addis Ababa University, 2023-03) Berhanu,Temesgen; Asres, Kaleab(Prof.); Bisrat, Daniel(Dr.)Helminthic infections are among the most widespread parasitic infections in humans. It is estimated that more than half of the world’s population suffer from parasitic infections. It poses morbidity particularly in children and pregnant women. Helminthic infections are more common in developing countries with poorer personal and environmental hygiene. Plant-derived drugs and herbal remedies remain important resources to alleviate and cure diseases, especially in developing countries. Variety of plants from various families including Ricinus communis from the family Euphorbiaceae are used to treat helminthiasis across the world. R.communis is an annual oilseed crop commonly known as castor. Antimicrobial, antifungal, anticancer, antidiabetic, anti-inflammatory and antimalarial are some of the pharmacological activities that have been reported from extracts of R. communis. In the present study, the petroleum ether seed extract of R. communis, its base hydrolysate and the major constituent of the hydrolysate were tested for their anthelmintic activities against the model organism Caenorhabditis elegans. The dried and powdered seeds were extracted using petroleum ether and then the oil collected was subjected to base hydrolysis to obtain the hydrolysate. Fractionation of the hydrolysate by column chromatography packed with silica gel 60-G resulted in the isolation of the hydroxylated fatty acid (9Z)-12-hydroxyoctadec-9-enoic acid (ricinoleic acid). The isolated free fatty was esterified by 5% Potassium hydroxide solution in methanol to get ricinoleic acid methyl ester. Structural elucidation of the compounds was achieved by spectroscopic techniques including ESI-MS, 1H and 13C-NMR spectral data. Results of the anthelmintic assay revealed that VIII ricinoleic acid and its methyl ester are strongly active against C. elegans worms compared to the oil. Ricinoleic acid exhibited 97% mortality at the tested concentration of (1 mg/ml). In conclusion, the present study demonstrated that the oil of R. communis seeds possesses strong anthelmintic activity against the model nematode C. elegans worms and the activity of the oil would be attributed to the presence of ricinoleic acid as a major constituent.Item Anti Tuberculosis Drug Induced Hepatotoxicity in Hiv Positive and Negative Patients(Addis Ababa University, 2005-06) Yimer, Getnet; Aseffa, Abraham(PhD)Anti-tuberculosis drug induced hepatotoxicity (DIH) is a common problem in the management of tuberculosis. This study was intended to identify possible risk factors for development of DIH, including degree of immunosuppression. In this prospective 2-month cohort study, 103 HIV positive and 94 HIV negative newly diagnosed tuberculosis patients were followed after initiation of DOTS (direct observed treatment short course). CD4 count was measured for the HIV positive patients. All patients were also evaluated for different risk factors including HBsAg, Anti-HCV, alcohol intake, use of other drugs including traditional medicines, acetylation status and presence of chronic illness. Patients were monitored biochemically (by liver function tests) and clinically for development of DIH weekly in the first month and bi-weekly in the second month after start of therapy. Biochemical hepatotoxicity was seen in 17.3% of the patients. CD4 counts of these patients were 0-50 for 7 (35%), 51-100 for 8 (40%), 101-200 for 4 (20%), and > 200 for 1 (5%). Three patients were positive for HBsAg and none had anti-HCV. Five patients died of non-hepatic causes among the patients who developed DIH. Eight out of the 34 patients with biochemical hepatotoxicity (23.5%) developed clinical hepatotoxicity that necessitated discontinuation of their anti-TB drugs. Seven of the eight were HIV positive, seven were female, and 2 were positive for HBsAg. Biochemical hepatotoxicity was significantly associated with HIV co-infection (p=0.002), concomitant drug intake (p=0.008), decrease in CD4 count (p=0.001), high mortality (p=0.001), and having Wt/Wt allele for acetylation status (p=0.026). Clinical hepatotoxicity is also significantly associated with being female (p=0.027), HIV co-infection (p=0.043), concomitant drug intake (p=0.003), HBsAg (p=0.046), decrease in CD4 count (p=0.025), and high mortality (p=0.0001). No significant association was seen between hepatotoxicity with alcohol intake, age, body mass index, type of TB and anti HCV positivity. The findings would assist in selectively managing patients at risk. It is recommended to have a regular biochemical and clinical follow up for those patients who are at risk of developing DIH .These patients include HIV positive patients, with special emphasis to those with a lower CD4 count, and patients who take drugs other than their anti TB medication. We also recommend that further work should be done to explore the reason for the observed association between DIH and female sex, HBsAg positivity, and acetylation status. Key words: Tuberculosis, HIV, Hepatotoxicity, Acetylation status, NAT2 geneItem Antidiarrheal Activity of Crude Extract and Coumarins from Psydrax schim- periana (A. Rich.) Bridson. Roots in Swiss Albino Mice, and Evaluation of Nu- tritional Composition and Anti-nutritional Factors of Its Fruits(Addis Ababa University, 2023) Damissie,Getahun; Hymete,Ariaya(PhD); Tadesse,Solomon (PhD); Tolossa,Ketema (PhD)Despite considerable improvements in the accessibility of medical services, diarrheal illnesses continue to claim the lives of children, accounting for up to 9% of all pediatric fatalities world- wide. The roots of Psydrax schimperiana is traditionally used to treat diarrhea and its fruits are consumed for nutritional purposes in Ethiopia. This study aimed to investigate in vivo antidiar- rheal activity of crude extract and coumarins isolated from the roots of P. schimperiana to pro- vide a pharmacological basis for its traditional use as diarrhea agent and to evaluate the nutri- tional composition and anti-nutritional factors from its fruits. Maceration with 80% methanol was used to prepare the crude extract from the powdered roots of P. schimperiana. The crude roots extract of P. schimperiana was tested for in vivo antidiarrheal efficacy in mice utilizing castor oil-induced diarrhea, gastrointestinal transit time and enteropool- ing models at doses of 100, 200, and 400 mg/kg. Phytochemical investigation of the crude roots extract led to the isolation of two coumarins, isoscopoletin and scoparone. The structures of these compounds were established by interpretation of their spectral data, and by comparison with data reported in the literature. Isoscopoletin and scoparone were evaluated for antidiarrheal activity against castor oil-induced diarrhea model at 10 mg/kg and 20 mg/kg doses. Moisture content, ash value, crude protein, crude fibers, crude fat, phytate, tannin, and oxalate contents of P. schimperiana fruits were determined according to the standard analytical proce- dure. All generated data were analyzed using SPSS software version 26. The crude root extract of P. schimperiana, at doses of 100, 200, and 400 mg/kg, inhibited defe- cation by 37.5%, 46.2%, and 61.2%, respectively. At a dose of 20 mg/kg, scoparone and isosco- poletin reduced defecation by 61.2% and 66.6%, respectively. ii Fruits from P. schimperiana contained 31% fiber, 9.19% crude protein, 12.40% moisture, 6.38% ash, and 0.99% fat. The fruits also contained the anti-nutritional factors phytate (1.16%), oxalate (0.72%), and tannin (22.96%). The study provides a scientific basis for further development and usage of the roots of P. schimperiana, and warrants continued investigation of isoscopoletin and scoparone toward development as a novel treatment for diarrheal diseases. The fruits of P. schimperiana can be considered as a beneficial source of vital nutrients such as carbohydrate, protein, and crude fibers. However, the higher tannin content may interfere with the absorption of essential minerals and inhibit effective utilization of proteinsItem Antidiarrheal Activity of the 80% Methanol Root Extract of Thalictrum ryhnchocarpum Dill. & A. Rich and Its Major Constituent Against Castor Oil- Induced Diarrhea in Mice(Addis Abeba University, 2019-12) Feyisa, Kebede; Prof.Asres, Kaleab; Dr.Bisrat, DanielDiarrhea is one of the main causes of infant mortality in Ethiopia and in many other developing countries, causing about 4 to 8 million deaths annually worldwide. Despite recent reductions in morbidity and mortality worldwide, diarrhea still remains one of the leading causes of death in developing countries. Like many other developing countries, people in Ethiopia strongly rely on the therapeutic benefits of traditional medicine to treat diarrhea. One such plant is Thalictrum ryhnchocarpum Dill. & A. Rich. Thus, in the present study, the 80% methanol extract of the root of T. ryhnchocarpum and the compound isolated thereof have been evaluated for their antidiarrheal activity. Phytochemical investigation of the 80% methanol root extract of T. ryhnchocarpum by preparative TLC over silica gel resulted in the isolation of one major alkaloid unequivocally identified as berberine using various spectroscopic techniques, including MS, 13 C-NMR and DEPT spectral data. Both the total extract and berberine were tested for their in vivo antidiarrheal activity on three models namely, castor oil-induced diarrhea, charcoal meal and enteropooling models in mice. It was shown that both the extract and berberine possess significant antidiarrheal activity in a dosedependent manner on all the tested models. Particularly, the root extract showed the maximum activity on castor oil-induced diarrhea model, with 71.4%, 74.0% and 78.0 % (P < 0.01) and berberine displayed even higher activity with 81.0%, 87.6 % and 88.3% at tested concentration of 100, 200 and 400 mg/kg, respectively. Antidiarrheal activity of the root extract and berberine was also noted on the other two models. When administered up to a dose of 2000 mg/kg, neither the root extract nor berberine showed acute toxicity in Swiss albino mice. In view of the present results, it can be concluded that the root extract of T. ryhnchocarpum and berberine could serve for the treatment of diarrhea thereby supporting the traditional claim of the plant against diarrhea.Item Antidiarrheal and Antispasmodic Activities of Stephania Abyssinica (Minspermaseae) Used In Ethiopian Traditional Medicine(Addis Ababa University, 2010-06) Deneke, Tatek; Engidawork, Ephrem(PhD)Diarrhea is a leading cause of morbidity and mortality in developing countries. Diarrhea may result from disturbance in bowel function in which case there is increased bowel transit, excessive intestinal secretion of water and electrolytes, decreased intestinal reabsorptions as well as more frequent defecations of loose, watery stool. Many plant preparations have claimed activities and traditional used as antidiarrhea and antispasmodic. S. abyssinica is traditionally used for treatment of diarrhea and stomachache in Ethiopia. The aim of this work was to evaluate the antidiarrheal and antispasmodic activities of the aqueous and methanol extract of the root and leaf of S. abyssinica. Antidiarrheal activities were studied in mice using castor oil-induced diarrhea at doses of 25, 50,100, and 200 mg/kg body weight. The extracts significantly prolonged the time of diarrheal induction, increased diarrhea free time, reduced the frequency of diarrhea episodes, decreased the weight of stool, and decreased general diarrheal score in a dose dependent way. With dose of 200 mg/kg the extracts produced higher in-vivo antidiarrheal index (ADI) than the reference loperamide. ADI of loperamide, SALM, SALA, SARM and SARA was 77.33, 88.79, 89.21, 91.08 and 82.23, respectively. In Entropooling test in mice the extract significantly (p < 0.01) inhibited intestinal fluid accumulations of mice in a dose dependent fashion; with dose of 100 mg/kg from1.03±0.093 ml of the control to 0.403±0.019ml, 0.210±0.018 ml, 0.494±0.012ml and 0.288±0.026ml by SALM, SARM, SALA and SARA respectively. The antispasmodic activity studies were performed as in vitro and in vivo models. The in-vitro antispasmodic activity studies were performed on isolated GPI. The methanol and aqueous extracts of the leaf showed significant and concentration dependent inhibition of acetylcholine induced contraction of isolated GPI. The extracts depressed Emax of Ach, and decreased PD2 value of the Ach. The Emax of Ach at conc of 10-3M is decreased (from100 for the control group) i viii by SALM with concentration of 200 and 100 ug/ml to 45.6±2.13 and 73.2±3.04 respectively, whereas by SALA with 200 and 100 ug/ml to 62.0±2.98 and 74.8±2.46 respectively. In the in vivo antispasmodic activity test, the extract significantly decreased the peristaltic index (PI). In normal transit test, the PI of SALM, SALA, SARM and SARA with dose of 200 mg/kg was all 0.00 (100% suppression of normal peristalsis). However in castor oil induced transit with dose of 200 mg/kg the peristaltic index (PI) of SALM, SALA, SARM and SARA was 26.67, 36.85, 22.00 and 40.65 respectively. The result of this study indicated that the plant extract possesses antidiarrheal and antispasmodic activities and proves the fact that this plant is used in traditional medicine for treatment of diarrhea, stomachache and abdominal cramp. Key words: S. abyssinica, antidiarrheal, antispasmodic, antienteropooling, aqueous and methanol extract, animal (mice or guinea pig)Item Antihypertensive Activity of Aerial Parts of Satureja Punctata (Benth.) Briq. (Lamiaceae)(Addis Ababa University, 2015-02) Hika, Debabe; Hymete, Ariaya(PhD); Yonathan, Mariamawit(PhD); Mammo, Wendemagegn(Professor)Satureja punctata Benth. Briq. (Lamiaceae) locally known as ‘‘Lomishet’’ is among the plants used in Ethiopian traditional medicine for the treatment of various diseases including hypertension. The current study aimed at evaluating the antihypertensive activity of the decoction of the aerial parts of this medicinal plant in guinea model of hypertension and its vasorelaxant effect on isolated aorta. Acute hypertension was induced by surgical procedures involving clamping of the left renal artery and blood pressure was recorded invasively by direct cannulation method from the right common carotid artery. Intravenous administration of the decoction at doses of 10, 20 and 30 mg/kg caused 13.66 ± 0.27, 34.35 ± 0.33, 45.78 ± 0.23% (n=6) fall in (p < 0.01) MABP, respectively, in normotensive guinea pig and a respective fall of 16.02 ± 0.28, 38.52 ± 0.50, 52.07 ± 0.42 % (n=6) (p < 0.01) MABP in renovascular hypertensive guinea pig. The decoction also caused a dose-dependent relaxation of aorta precontracted with KCl at a concentration of 2.5- 40 mg/ml, with a maximum relaxation of 98.19 % achieved at 40 mg/ml. Preparative reversed-phase HPLC analyses of the aerial part decoction of S. punctata resulted in isolation of two phenolic compounds, rosmarinic acid and linarin. The structures of these compounds were elucidated by utilization of spectroscopic techniques, i.e., MS, UV, IR, 1D, and 2D NMR. Further, rosmarinic acid showed significant (p<0.01) reduction of MABP by 8.14 ± 0.27, 15.79 ± 0.33 and 31.78 ± 0.64 % (n = 6) at doses of 0.75, 1.5 and 3 mg/kg, respectively, in normotensive guinea pig. The findings of this study suggest that the aerial parts of S. punctata have genuine antihypertensive activity.Item Antimalarial activity of the root extract of Lobelia giberroa Hemsl. and its major constituent against Plasmodium berghei infection in mice.(Addis Abeba University, 2021-10) Tadege, Getnet; Prof. Hymete, Ariaya; Dr.Tadesse, SolomonLobelia giberroa Hemsl. is an indigenous plant in Ethiopia. Ethiopian traditional healers use its different parts to treat malaria, bacterial and fungal infections, and cancer. For treatment of malaria, in particular, the traditional healers utilize the plant’s root parts. This study was carried out to investigate the antimalarial activity of L. giberroa. The roots of L. giberroa were extracted using 80% methanol and the hydroalcoholic extract was successively fractionated with hexane, ethyl acetate, methanol and water. Chromatographic and spectroscopic methods were used to isolate and identify the active compound from the methanol fraction. Acute oral toxicity study was conducted on the hydroalcoholic extract, solvent fractions, sub-fractions and the isolated compound. The hydroalcoholic extract and the isolated compound were evaluated for antimalarial activity using the standard four-day suppressive method, Rane’s and prophylactic tests in Plasmodium berghei infected albino mice. The solvent fractions and sub-fractions from column chromatography were evaluated for antimalarial activity using four-day suppressive method. The hydroalcoholic extract, solvent fractions, subfractions and the isolated compound were found to be safe at a dose of 2000 mg/kg. The hydroalcoholic extract of L. giberroa root and its methanol fraction exhibited the highest antimalarial activity and significantly increased the mean survival time of the treated mice. In fact, the hydroalcoholic extract exhibited 73.05%, 49.35% and 43.16% parasitemia suppression for four-day suppressive test, Rane's test and prophylactic test, respectively. The methanol fraction demonstrated 64.37% parasitemia suppression for four- day suppressive test. The isolated compound, characterized as lobetyolin, suppressed the level of parasitaemia by 39.96, 53.46 and 68.21% at a dose of 25, 50 and 100 mg/kg, in standard four-day suppressive test, respectively. Mice treated with 100 mg/kg/day lobetyolin survived longer (18.6 days) when compared with negative control group (6.8 days). In conclusion, the current study supports the traditional use of the plant for the treatment of malaria and identified the main active compound lobetyolin, the potential to be an antimalarial lead for further development. The active ingredient, lobetyolin, was also isolated for the first time from the root of Lobelia giberroa. To the best of our knowledge, this is the first report on the biological activity of L. giberroa.Item Antiprolif-erative Constituents of Roots of Podocarpus falcatus (Thunb.) R.Br. ex Mirb(Addis Ababa University, 2015-06) Mekuria, Ermias; Hymete, Ariaya(PhD); Yonathan, Mariamawit(PhD)Once thought of as the disease of the developed, cancer nowadays is becoming the prob-lem of every nation across the globe claiming millions of lives every year. Incidence, and thus prevalence, is increasing every year due to adoption of lifestyle factors that are known to be major cancer risk factors. Making things worse is the development of MDR to the known effective anticancer drugs. Moreover, the currently available drugs are cost-ly and are associated with severe side effects. Thus, discovering new anticancer drugs with new and safe modes of action is urgently needed. Natural products derived from medicinal plants are well-known contributors of clinically useful anticancer drugs; suffice to mention taxol, the Vinca alkaloids, podophyllotoxin and camptothecin and their de-rivatives. Relying on traditional medicines for most of their health needs, Ethiopians use various plants for prevention and treatment of cancer. For example, the roots of Podocar-pus falcatus are used as “anticancer” remedies in some parts of Ethiopia, which formed the basis of the present study to isolate the “responsible” “bioactive” compounds. Bioassay guided fractionation using the human colorectal adenocarcinoma (HT-29) cell line of the methanol extract of dried roots of P. falcatus (Podocarpaceae) led to the isola-tion of two new type C nagilactones, 16-hydroxy nagilactone F (PF-1) and 2β,16-dihydroxy nagilactone F (PF-3) and a new totarane-type bisditerpenoid 7β-hydroxy mac-rophyllic acid (PF-2), along with the seven known compounds: inumakinol D (28), mac- rophyllic acid (37), nagilactone D (41), ponasterone A (94), 2β-hydroxy nagilactone F (108), nagilactone I (109), and 15-hydroxy-nagilactone D (110). The structures of the new compounds were determined by 1D and 2D-NMR, HRESIMS and by comparison with the reported spectroscopic data of their congeners. The orientation of the hydroxyl group at C-2 of 108 and 109 was revised to be β based on evidence from detailed analysis of 1D and 2D-NMR data and single crystal X-ray diffraction studies. Among the isolated compounds the nagilactones, including the new dilactones 16-hydroxy nagilactone F (PF-1) and 2β,16-dihydroxy nagilactone F (PF-3), were the most active (ED50 0.3–5.13 μM range) against the HT-29 cell line, whereas the bisditerpenoids (PF-2 and 37) and the other known compounds 28 and 94 were inactive. The presence of bioactive nagilactones in P. falcatus supports its traditional use.Item Antiproliferative Activities of Alkaloids from Crinum abyscinicum Hochst. ExA. Rich Bulb Extract(Addis Abeba University, 2019-08) Abebe, Besufekad; Prof.Hymete, Ariaya; Dr.Bisrat, DanielCancers are group of diseases that are distinguished by increased division of cells caused by genetic changes. Globally, it accounted for 9.6 million deaths in 2015 and is increasing to be a public health burden. Yet the treatment of cancer is mainly through chemotherapy that possesses severe toxicities and facing multiple drug resistance. These problems have urged researchers to look for safe and effective chemotherapeutic agents from natural products, especially from plants. Thus, Crinum abyscinicum as one of such plants in Ethiopia that has been used traditionally for treatment of cancer was evaluated for its antiproliferative activity. In vitro antiproliferative activity of the bulb extract of C. abyscinicum was investigated using MTT and resazurine assays on ovarian carcinoma cell line (A2780) and leukemia cell line (MV4-11) respectively. It is noted that the bulb extract possesses antiproliferative activity with GI of 8.289 ± 0.33µg/ml and 20.77 ± 0.354µg/ml against leukemia cell line (MV4-11) and ovarian carcinoma cell line (A2780) respectively. 50 Further analysis of the bulb extract using preparative thin layer chromatography (PTLC) resulted in the isolation of two alkaloids. The structure of the alkaloids were characterized as 6hydroxycrinamine (BCA-1) and lycorine (BCA-2) using spectroscopic methods including HRTOF-MS, 1D-NMR ( 1 H, 13 C-NMR and DEPT) and 2D-NMR (HMBC) spectral data, and by comparison with reported spectroscopic data for the same compounds. Among the isolated compounds, lycorine displayed antiproliferative activity in a dose-dependent manner against MV4-11 and A2780 cell lines with GI of 3.372 ± 0.26733µg/ml and 2.849 ± 0.139µg/ml respectively. Likewise, 6-hydroxycrinamine exhibited activity with growth inhibition of 5.323 ± 0.455µg/ml and 2.925 ± 0.769µg/ml against MV4-11 and A2780 respectively. The activity observed for the bulb extract as well as isolated compounds of C. abyscinicum support the traditional use of the plant against cancer.Item Antiproliferative Activity of the Leaf Latex of Aloe secundiflora Engl. and its Major Constituents(Addis Ababa University, 2023-01) Berie,Yabibal; Tadesse,Solomon( PhD); Ayalew,HiwotGlobally, an estimated 19.3 million new cancer cases and almost 10.0 million cancer deaths occurred in 2020. The various methods of treatment of cancer that can be employed alone or in combination, depending upon different factors, are chemotherapy, radiotherapy and surgical interventions. The currently available chemotherapeutic agents have severe toxicities and face multiple drug resistance. This calls for researchers to look for safe and effective chemotherapeutic agents from natural products. Thus, the antiproliferative efficacy of Aloe secundiflora, a plant traditionally used to treat cancer, was evaluated. The antiproliferative activity of A. secundiflora leaf latex was investigated against four cancer cell lines, breast (MCF-7), lung (A427), urinary bladder (RT-4), and cervical (SiSo) using MTT assay. The latex possesses better antiproliferative activity with an IC50 value of 15.3 μg/mL against the A427 cell line over the other three cell lines. Phytochemical analysis of the latex using preparative thin layer chromatography resulted in the isolation of two glycosides and the structure of these two glycosides were characterized as Aloenin B and Aloeresin D using spectroscopic methods, and by comparison with reported spectroscopic data. Aloenin B and Aloeresin D displayed antiproliferative activity against A-427 cell lines with IC50 value of 3.2 and 5.5 μg/mL, respectively. The activity observed for the latex as well as isolated compounds of A. secundiflora support the traditional use of the plant against cancerItem Antiprotozoal Activity of Extracts and a Major Compound from the Leaves of Ranunculus multifidus Forrsk.(Addis Abeba University, 2021-06) Sirak, Betelhem; Asres, Kaleab(Professor)Protozoal diseases caused by the genera Leishmania, Plasmodium and Trypanosoma have devastating impact mostly on the poorest countries of the world due to their prevalence, virulence and drug resistance ability. This calls for the development and discovery of new effective and safe chemotherapeutic agents from alternative sources such as medicinal plants. This study aimed at investigating the antiprotozoal activity of Ranunculus multifidus Forrsk. (Ranunculaceae), a medicinal plant used to treat leishmaniasis, malaria and trypanosomiasis in several African countries. Fresh leaves of R. multifidus were subjected to maceration using 80% methanol and hydrodistillation to obtain hydroalcoholic extract (RM-M) and hydrodistilled extract (RM-H), respectively. Antileishmanial activities of the extracts were studied on clinical isolates of the promastigote and amastigote forms of Leishmania aethiopica and Leishmania donovani, whilst 4-day-suppressive, Rane’s and prophylactic tests were employed to investigate in vivo antimalarial activity against chloroquine sensitive Plasmodium berghei infected mice. In vitro and in vivo antitrypanosomal effects of the extracts were also investigated against Trypanosoma congolense field isolate. Results of the study revealed that both extracts were active against the studied protozoans, although RM-H demonstrated superior activity (p < 0.001) compared the RM-M. The IC 50 values of RM-H were 0.490 and 0.984 μg/ml against promastigotes and 1.49 and 1.84 μg/ml against macrophage amastigotes of L. aethiopica and L. donovani, respectively. At a dose of 35.00 mg/kg/day, RM-H demonstrated a chemosuppression value of 70% in 4-day-suppressive test. Furthermore, at a concentration of 4 mg/ml, RM-H ceased motility of T. congolense within 20 min. Further phytochemical analysis of RM-H using preparative thin layer chromatography (PTLC) led to the isolation of an α,β-unsaturated dilactone characterized as anemonin on the basis of FT-IR, APCI-MS, 1D- and 2D-NMR spectral assignments and also by comparison with the reported spectroscopic data of the same compound. Anemonin displayed significant (p < 0.001) antileishmanial activity with IC 50 of 1.33 nM and 1.58 nM against promastigotes and 1.24 nM and 1.91 nM against amastigotes of L. aethiopica and L. donovani, respectively. Anemonin was found to be relatively less toxic to macrophage cells with selectivity indices (macrophage cytotoxic/antileishmanial ratios) of 22 and 14, respectively. In a 4-day suppressive, Rane’s and prophylactic antimalarial tests, anemonin showed median effective doses (ED 50 s) of 2.17, 2.78 and 2.70 μM, respectively. At a concentration of 4 mg/ml, anemonin completely immobilized trypanosomes within 5 min of incubation, while the standard dug diminazene diaceturate immobilized the parasites within 10 min. In the in vivo antitrypanosomal assay, anemonin eliminates parasites at all the tested doses (8.75, 17.00 and 35.00 mg/kg/day) and prevented relapse. Results of the present study provided evidence that the leaves of R. multifidus possess genuine antileishmanial, antiplasmodial and antitrypanosomal activities, which may be attributed to the presence of anemonin. Thus, use of the plant in traditional medicine for the treatment of protozoal diseases seems to be well founded. valuesItem Appropriateness of Type 2 diabetes mellitus drug therapy: A case of Tikur Anbessa Specialized Hospital Diabetes Clinic(Addis Ababa University, 2014-03) Ayele, Alemseged; Engidawork, Epherm(PhD); Yifter, Helen(PhD)Background: Diabetes mellitus (DM) is a metabolic problem involving chronically high blood glucose levels or hyperglycemia, which is thought to arise from insulin deficiency. This insulin deficiency can be decrease in amount or a complete absence in body. In the long run high blood glucose level could lead to various complications. Beside altered glucose metabolism carbohydrate, protein, and lipids metabolisms are also affected in diabetes mellitus. Objective: To assess appropriateness of Type 2 diabetes mellitus drug therapy (T2DM) and investigate association between fasting blood glucose (FBG) and the patients’ clinical and demographic characteristics at the diabetes clinic of Tikur Anbessa specialized hospital (TASH). Methods: The study was a cross sectional hospital based survey and used both quantitative and qualitative methods. T2DM patients who came for their follow up treatment at the diabetes clinic of TASH over a one month period (April 2013) were used as research participants. Plus key informant interview with the help of semi-structured open ended questioner was used focusing on the experience and practice physicians within the diabetes clinic regarding medication choice and guidelines they use. Results: A total of 103 patients enrolled in the survey and the proportion of females (59.2%) was higher than males (40.8%). The mean age was 52.2 years and most of them live in Addis Ababa. When it comes to clinical characteristics mean FBG was 155.99 ± 44.32 mg/dl, the difference in FBG between male and female was insignificant (P=0.325). Body mass index (BMI) had a mean value of 26.4± 3.05 kg/m2 and 51.45% of the patients were overweight. Medication wise NPH (56.3%), metformin plus glibenclamide (19.4%) and metformin (10.7%) were the most prescribed drug therapies. And 3.88% of patients were only on glibenclamide. The association of gender, age, BMI and medication used with the FBG levels of patients was not significant with a p value of 0.6, 0.803, 0.97 and 0.081 respectively. The key informants point out that patient load, physician rotation, lack of guide-line and devices as a reason for inadequacy of treatment. Conclusions: The treatment of T2DM is appropriate with existing problems. Metformin was the first choice oral medication, while most patients were on NPH. And no single factor was associated with influencing the FBG of patients. Key Words: Type 2 diabetes mellitus, Drug therapy AcknowledgmentsItem Assessment of Drug Therapy Problems and Contributing Factors among Adults Admitted to Tirunesh Beijing General Hospital, Addis Ababa, Ethiopia(Addis Abeba univerisity, 2021-11) Ababiya, Tsegaye; Mekuanint, SolomonThe philosophy of pharmaceutical care (PC) is the sum of responsibilities of the pharmacist to meet all of the patient’s drug-therapy needs through direct patient care and cooperation with other facets of the health care. It is important to avoid drug therapy problems (DTPs) as they may cause morbidity and mortality, reduce quality of life and increase health expenses for the patient and for society. This study aimed to assess DTPs and associated factors among adults admitted to Tirunesh Beijing General Hospital. A prospective cross-sectional study was conducted on 220 adults admitted to medical ward of TBGH. Cippole`s DTPs classification system was used for identification, intervention and documentation of DTPs. Thirty-eight percent of patients encountered at least one DTP and 298 DTPs were identified in 177 patients (104 males and 73 females) with prevalence of 80%. Out of 1467 drugs prescribed, 62 drugs were significantly associated with the occurrence of DTPs. ‘‘Needs additional drug therapy” (36.9%), was the most frequently identified DTPs followed by ‘‘inappropriate dose’’ (19.8%) and “noncompliance” (19.5%). Hospital stay more than seven days (AOR=3, 95% CI:1.394-5.843; p=0.004) and polypharmacy (AOR=2, 95% CI: 1.168-5.287; p=0.019) were potential risk factors for the occurrence of DTPs. In conclusion, there is high prevalence of DTPs, with the most frequent one being needs additional drug therapy followed by inappropriate drug therapy and noncompliance. Polypharmacy and number of hospital stay were potential risk factors for the occurrence of DTPs. In recommendation, all stake holders should work in collaboration to combat drug therapy problems as it poses harm and poor quality life to patients and great attention should be given for those drugs which are associated with the occurrence of DTPs.Item Assessment of Knowledge, Attitude and Practices on Adverse Drug Reaction Reporting among Pharmacy Personnel Working at Community Pharmacy, Addis Ababa, Ethiopia(Addis Ababa University, 2015-05) Goshime, Alaynesh; Gedif, Teferi (PhD)Assessment of Knowledge, Attitude and Practice on Adverse Drug Reaction Reporting among Pharmacy Personnel Working at Community Pharmacy, Addis Ababa, Ethiopia Alaynesh Goshime Addis Ababa University, 2015 Modern medicines have changed the way in which diseases are managed and controlled. However, despite all their benefits, evidence continues to mount that adverse drug reactions (ADRs) are common cause of illness, disability and even death. Knowledge, attitude and practices of health professionals towards ADR reporting are known to have crucial contribution in the detection and reporting of the reactions. A cross sectional study was conducted on a sample of 379 pharmacy personnel working at randomly selected community pharmacies of Addis Ababa to assess their knowledge, attitude and practice towards ADR reporting. Data was collected using self administered questionnaire. Majority of the respondents were male (57.5%) and in the age group 26-30 (55.1%). Over half (70.7%) of the respondents had poor knowledge. One hundred seventy three (45.6%) participants encountered ADRs in the past 12 months but none of them reported to the relevant authority. The majority of respondents (82.8%) had a positive attitude towards ADRs reporting. The study revealed that majority of pharmacy personnel at community pharmacy in Addis Ababa had poor knowledge, positive attitudes and very limited practices towards ADR reporting. The Ethiopian Food, Medicine and Health Care Administration and Control Authority should create awareness iv on the existence of ADR monitoring system and the purpose and importance of ADR reporting and should also conduct continuous trainings and seminars about ADR reporting with community pharmacies dispensers and finally ADR reporting forms should be made available at community pharmacies. Keywords: Pharmacovigilance , ADR reporting, Community Pharmacy Personnel, Knowledge, Attitude, PracticeItem Characterization of the Short-Term Effects of Prenatal Asphyxia and Screening of Some Ethiopian Medicinal Plants for the Probable Preventive Role in Rats.(Addis Ababa University, 1997-04) Engidawork, EpbremPerinatal asphyxia results from failure of normal respiratory gas exchange during or soon after labor and it remains an important cause of permanent neurological deficit in surviving infants. The most common features are hypoxia, hypercapnia, and metabolic acidosis. The present sf1ldy was undertaken to fUrther characterize the short-term effect of perinatal asphyxia and to investigate a possible preventive role of some Ethiopian medicinal plants and hypothermia in rats. The effect of perinatal asphyxia on survival pattern, brain and heart pH, levels of amino acids, monoamines, and glycolytic intermediates was studied using in vivo microdialysis and ex vivo biochemistry. Perinatal asphyxia was induced by immersing fef11S containing uterus horns, obtained by cesarean section from term pregnant rats, in a water bath at 370C for different periods (0-23 min), according to a non-invasive model that largely mimics the conditions resulting in asphyxia during human labor (Bjelke et al. , 1991; Andersson et aI., 1992; Herrera-Marschitz et al., 1993). Subcutaneous levels of pyruvate, lactate, glutamate, and aspartate were monitored with microdialysis 80 ~lin-8 days following delivery. In parallel experiments, pups were sacrificed 40 min after delivery and the brain and heart were removed to measure pH In addition, pups were also sacrificed 80 min-8 days after delivery and the brain was removed to measure striatal levels of pyruvate, lactate, glutamate, aspartate, and monoamines. At 37°C, a decrease in the rate of sU/vival was first observed following asphyxic period longer than 16 min and no survival was observed after 22 min. pH decreased with the length of asphyxia. In control pups (cesarean delivered), brain pH was (7.3±0.01;N=6) and heart pH was (7.35±0.01; N=6). A significant decrease in pH was observed following 10-11 min and 5-6 min, in brain and heart respectively. After 80 min of delivery, a significant increase in the levels of all the measured compounds, in subcutaneous and brain tissues, were observed follOWing exposure to mild asphyxia. However, the levels started to decline when asphyxia was prolonged With increasing age, the levels of the measured compounds in mild • asphyxic pups were almost similar as that of the control pups. Nonetheless, the time needed to recover depended upon how greatly the compound's metabolism was affected Lactate being the most severely affected, much time was needed to reduce its level. Thus, changes in systemiC pH, glycolytic intermediates, monoamines, and excitatory amino acids metabolism were observed following perinatal asphyxia. In particular, subcutaneous level of lactate preceded: (q) a decrease in brain pH, (b) an increase in brain lactate level, (c) a decrease in the rate of survival, and probably (d.) brain damage. The possible protective effect of some herbal medicines was evaluated by injecting the extract subcutaneously or using as a bathing fluid and subjecting the pups to asphyxia at 370 C. Asphyxia induction at 300C and I50C was also carried out to evaluate the protective effect of hypothermia and to use it for comparison purpose. Survival was prolonged when asphyxia was induced under hypothermic condition. No survival was observed after 50 min and 140 min when asphyxia was induced at 300C and I50C respectively. Survival pattern after treatment with plant extracts did not show any significant difference compared to saline injected control group. Thus, hypothermia seems the only intervention that can provide good protective effect amongst the interventions so far evaluated. However, with improvement in obstetric management, its role has been shown to be limited. As early as the 1930s, the cause of petlnatal brain damage was intimately tied up with attitudes towards the use of sedatives, analgesics, and anesthetics duriug labor and delivery (Eastman, 1936). It was demonstrated that the excessive use of these agents caused "apnea neonatomm" which was thought to be the principal cause of cerebral injwy (Sclueiber, 1938) and almost all Wliters of the time suppOlted this view and equated "asphyxia neonatorum" with "apnea neonatorwn". Although this view was later shown to be unlikely (Myers, 1977), the tendency to consider birth apnea as a causative factor for cerebral injmy dominated-the 1940s-and the 1950s-. - Hence, articles appeared in the I 940s strongly suggested a causal relationship between petlnatal asphyxia and cettain patterns of nemopathogenic changes in the brain. It was stated that the brain swelling and necrosis obsetved in newborns who died after cesarean delivety because of premature detachment of the placenta was due to asphyxia (Clifford, 1941). The injwies at buth were thought to be associated either to trawna to the head or to fetal systemic hypotension caused by asphyxia (Malamud, 1959,1963; Norman, 1969). It was believed that cerebral venous congestion causes the haemorrhagic infarction that often affects the brains ofbitth-injw·ed babies (Schwartz, 1961). The congestion was atttibuted to the rapid passage of the fetal head ii-om a wne of high pressure within the utems to one oflow pressw·e outside (Schwaltz, 1961). The infarction of the cerebrum associated with birth injwy was caused by fetal circulatOlY failure, generalized venous congestion, and cerebral venous stasis-thrombosis (Towbin, 1970). Thus, a nwnber of causes have been proposed for petlnatal brain damage of which petlnata1 asphyxia is one of the candidates. Asphyxia is defined as suffocation with anoxia and increased carbondioxide. It atises from impairment of normal respit·atOlY gas exchange with resulting hypoxia/ischemia, hypercapnia, and metabolic acidosis. The term perinatal asphyxia is often used to indicate an impainnent of gas exchange during or soon after labor (Nelson and Leviton, 1991; Martin and Nelson, 1993). The tenn hypoxic-ischemic or postasphyxial encephalopathy is often used to describe the illness thought to stem from such impaiIment. In most instances, during the peIinatal peIiod, hypoxemia and/or ischemia occm as a result of asphyxia (Hull and Dodd, 1991). When descIibing oxygen deptivation in hllJDan, the tenn asphyxia is used, because it is not known whether the insult is hypoxic, ischemic, or more probably a combination. Fmthennore, regarding the fetus, the telms hypoxia and ischemia have been used interchangeably, because, the most common cause of hypoxia in the fetus is hypoperfusion or ischemia. Hypoxia can also cause ischemia, as it is capable of producing hypotension and reduced cardiac output. Thus, in asphyxia, the major additional feature is hypercapnia, which results in a nllJDber of other metabolic disorders, such as acidosis and physiological effects including cerebral vasodilatation (Volpe, 1987). Hypoxia and partial regional ischemia commonly occm together, therefore, it appears that the regional distIibution of ischcmia in the face of hypoxia is a major determinant of the relatively selective nature of peIinatal asphyxial brain injury. Hence, this type of brain injmy is refelTed to as hypoxic-ischemia. PelIDatal asphyxia can occm in the human fetus or neonate as an acute total asphyxial episode resulting ii-om cord prolapse that leads to complete cessation of blood flow (Leech and Alvord, 1977), and as a prolonged partial asphyxial episode resulting from placental abruption that may occm during a long and complicated labor (Clifford, 1941). In order to understand the patterns of pelIDatal brain damage, two models in monkeys have been developed: acute total asphyxia (Ranck and Windle, 1959) and prolonged partial asphyxia (Brann and Myers, 1975; Myers, 1972, 1977). The first model that replicated acute total asphyxia caused a lesion affecting spinal cord, brainstem and thalamus without brain swelling. TIle second model that replicated prolonged partial asphyxia, however, produced a different pattern of cerebral affecting mainly the COltiCal and subcortical stmctures with brain swelling (Myers, 1972). The reason for the different distribntion of the lesions depends upon the redistribution of regional cerebral blood flow and the degree of neuronal maturation dwing asphyxia. In most cases, tbe total pelinatal insnlt in hmnans most likely resnlts from prolonged partial asphyxial episode, and sometimes from partia~ combined with terminal acnte asphyxial episode (Scott, 1976; Braun, 1986). Heuce, fetal partial asphyxia of any cause, independent offetal circnlatOlY collapse and head compression, is believed to be the Priru31Y event that sets in motion a vicious cycle ofbraiu swelling, leading to stasis of blood flow and, fiually to cerebral necrosis (Br3lill and Myers, 1975). IufOlmatiou about the specific effect of birth asphyxia on the fetus or neouates has beeu possible only since the development of new techniques for detennining blood pH and blood gases. The introduction of risk scoring and assessment of fetal behavior has finther improved the identification of the fetus at risk for a.phyxia (Brallll, 1986; Lowet ai, 1992). Thus, Apgar (1953) developed a SCOling system to infer the occurrence of birth asphyxia and to quantifY its sevelity from several indicators, such as: (i) type of breatlling; (ii) healt rate; (iii) color of the skin; (iv) muscle tone; and (v) response to different sensory stimnli. UnfOltwlately none of these indicators is an accurate predictor of outcome, rather they are probably best used to indicate the need for active resuscitation (Hnll and Dodd, 1991). Biochemical data such as umbilical pH and gas levels obtained soon after birtb may be used to validate the judgement tbat the pathophysiological changes obselved during birth 31'e asphyxial in natme. But these putative markers of asphyxia do not always conelate well with one another. Because of the poor predictive value of the traditional indicators, alternativesand Sarnat, 1976). HIE develops in the first few hours and days of life and is characterized by abnonnalities of tone, feeding, level of consciousness, and in the more severe cases, seizures and finally coma with the need for ventilatOlY support. The postasphyxial encephalopathy is graded into mild (no seizure), moderate (seizures) and severe (coma). Those infants with mild encephalopathy have a unifonnly good outcome, those with moderate encephalopathy have a 20-30% chance of severe handicap, and the majOlity of infants with severe encephalopathy die (Hull and Dodd, 1991). Hence, HIE has been found to be a much more accurate predictor of outcome (Robertson and Finer, 1985), however, the recent identification of a group of infants with typical encephalopathies (Hull and Dodd, 1991), without previous evidence of asphyxia cast some doubt on the casual relation between the two phenomena. Thus, there is still no reliable clinical indicator of birth asphyxia. Nevertheless, with the development of magnetic resonance spectroscopy, a potential independent indicator of brain asphyxial states has emerged (Martin and Nelson, 1993). Several animal models have been developed to assess the role of asphyxia in mediating brain damage (see Raju, 1992). In the present thesis, the short-telm effect of perinatal asphyxia and its prevention was studied in rat using a novel non-invasive model that largely mimics the conditions resulting in asphyxia during human labor (Bjelke etaI., 1991; Anderson etal., 1992; Herrera-Marschitz etaI., 1993) sought. This effort led to the identification of the abnOlmal neurological signs known as hypoxic-ischemic encephalopathy (HIE), that was used as an assessment of asphyxia (SamatsinewyItem Drug Susceptibility Pattern of Mycobacterium Tuberculosis Isolates In Addis Ababa(Addis Ababa University, 2005-07) Asmamaw, Dawit; Aseffa, Abraham(PhD); Makonnen, Eyasu (Professor)Background:-Addis Ababa, the capital city of Ethiopia, has an estimated population of 3.5 - 4 million. Previous reports on anti-TB drug resistance suggested an increasing trend of anti-TB drug resistance despite differences in the methodology. A study in previously treated individuals also suggested an increased incidence of Rifampicin (RMP) and Isoniazid (INH) resistance in individuals treated with fixed dose combination (FDC) anti-TB drugs. Objectives:-To determine the prevalence of resistance to the four first line anti-TB drugs and to see whether there is association between HIV and drug resistance. Methods: - A cross-sectional survey on anti-TB drug resistance was done in 19 health centres (out of 21) and 3 hospitals in Addis Ababa. Sputum and serum was collected from each patient. Sputum was digested and decontaminated using Petroff’s method with 4% NaOH and inoculated on to Lowenstein Jensen media. Proportion method with Middlebrook 7H10 media & 10% OADC enrichment was used for drug sensitivity determination. HIV testing was also done for each patient with rapid assays (Determine®, Capillus® and Unigold®). Species identification was done with a combination of Thiophene-2- Carboxylic acid Hydrazide (TCH) test and species specific PCR amplification (pncA gene) Results & Discussion :-269 (242 new and 27 previously treated) patients were included in the study. Out of these, 75% were culture positive. Sensitivity result was available for 173 isolates from new cases and 19 isolates from previously treated patients. Among the isolates from new patients 78.6% were sensitive to all drugs tested and 21.4% were resistant to any one drug while these figures in previously treated patients were 47.4% and 52.6% respectively. Prevalence of MDR-TB among new cases was 0.6% (1 isolate). Resistance to RMP, INH, Streptomycin (STM) and Ethambutol (EMB) was 1.2%, 13.3%, 16.8 and 3.5% respectively. In previously treated patients RMP, INH, STM and EMB resistance was 5.3%, 36.9%, 52.6% and 11.1% respectively. The prevalence of resistance in a similar survey conducted in 1998 was lower and the increase in the current study was statistically significant for any type of resistance, any EMB resistance, any STM resistance and resistance to multiple drugs. However the prevalence of RMP resistance and multidrug-resistant (MDR) TB was not changed. There was also no association observed between drug resistance among new cases and HIV. Conclusion:- Multidrug-resistance did not show increase in the city particularly in the last six years, compared to the previous reports. However non-MDR type of drug resistance, precursor of MDR, is on the rise.Item Ethnopharmacological Survey of Medicinal Plants among the Hamer Ethnic Group, Hamer Woreda, South Omo Zone, SNNPR, Ethiopia and Evaluation of a Selected Plant for its Antimalarial Activity(Addis Ababa University, 2012-07) Paulos, Biniam; Asres, Kaleab (PhD); Gedif, Teferi (PhD)Health seeking behaviour of people around the globe will be affected by different socio-cultural and economical factors. People in Ethiopia, particularly tribal people have long history of using medicinal plants as a major component of their traditional medical practices over many centuries to satisfy their health care needs. The transfer of this sort of knowledge from generation to generation is mainly effected by words of mouth. Cross-sectional survey was conducted to document ethnopharmacological information of the Hamer semi pastoralists by using semi structured questionnaires administered to eight traditional healers/key informants and one thousand six hundred household (HH) respondents supplemented by eight focus group discussions (FGDs). The majority (84%) of HH respondents were males, 94.4% of whom suffered illnesses in the last two weeks recall period and had taken action. The prevalence of the use of traditional medicine among the Hamer community was found to be very common as indicated by FGD participants, key informants and HH respondents. HH respondents reported that traditional medical practices are their first choice when family members get sick. Females’ preference of traditional medical practices was higher than males. The main reasons for the preference of the community members to traditional medical practices include its effectiveness, low cost and ease of availability. A total of sixty medicinal plants were reported and collected along with their local names, indication(s), parts used and method of preparations. The health seeking behavior of the Hamer ethnic group is affected by different socioeconomic and cultural factors. There is also a strong indication for traditional medical practices and use of plant materials to treat various ailments and health problems among the study population. Therefore, due attention should be given to these traditional medical practices. The ethnopharmacological survey part of this study revealed that Aloe otallensis Baker., an indigenous Ethiopian plant, was among the most widely used medicinal plants by the members of the Hamer Ethnic Group. The plant is used for the treatment of malaria and wound healing. Malaria, a diseases caused by protozoan parasites is a major obstacle to the socioeconomic xii development of several developing countries including Ethiopia. The phytoconstituents of A. otallensis studied by thin layer chromatography (TLC) and its antimalarial and antioxidant activities were assessed by in vivo four day Plasmodium berghei suppressive test and 1,1- diphenyl-2-picrylhydrazyl (DPPH) assay, respectively. The study revealed the presence of picataloside (2,8-O,O-di (β-D-glucopyranosyl)-1,2,8-trihydroxy-3-methylnaphtalene) in the exudate of A. otallensis, which was isolated from the plant for the first time. The study further showed that the leaf exudate of the plant possesses maximum antimalarial activity (60.7% suppression) at a dose of 300 mg/kg. Similarly, at a dose of 100 mg/kg the isolated compound suppressed P. berghei parasites by 47.9%. Both the exudate and the isolated compound displayed comparable radical scavenging activity possessing IC50 value of 26.9 and 26.2 μg/ml, respectively in DPPH assay. The results of the present study do seem to justify the traditional use of A. ottalensis for the treatment of malaria.Item Evaluation of Antidiabetic, Antihyperlipidemic, and Antiglycation Effect of Moringa stenopetala (Baker f) Cufodontis leaves(Addis Ababa University, 2016-03) Toma, Alemayehu; Makonnen, Eyasu (Professor); Mekonnen, Yalmetsehay(Professor)Background: Moringa stenopetala has been used in traditional health systems to treat diabetes mellitus. One of the successful methods to prevent onset of diabetes is to control postprandial hyperglycemia by inhibition of α-glucosidase and pancreatic α-amylase activities, resulting in the aggressive delay of the carbohydrate digestion of absorbable monosaccharides. The aim of the present study was to investigate the effect of the extract of the leaves of Moringa stenopetala on glycation control, α-glucosidase, pancreatic α- amylase, pancreatic lipase, and pancreatic cholesterol esterase activities, and, therefore find out the relevance of the plant in controlling blood sugar and lipid levels. Methods: The dried leaves of Moringa stenopetala were extracted with hydroalcoholic solvent and the resulting extract was dried using rotary vapor under reduced pressure. The dried extracts were determined for the total phenolic compounds, flavonoid content and condensed tannins content using Folin-Ciocateu’s reagent, AlCl3 and vanillin assay, respectively. The dried extract of plant-based food was further quantified with respect to intestinal α-glucosidase (maltase and sucrase) inhibition and pancreatic α-amylase inhibition by glucose oxidase method and dinitrosalicylic (DNS) reagent, respectively. Aqueous ethanol and n-butanol fraction of Moringa stenopetala leaves (500mg/kg body weight) and metformin (150 mg/kg body weight) were administered to diabetic rats. Blood glucose, lipid profiles, liver and kidney function were examined after 14 days of experiment. The antioxidant activity was determined using 2, 2′- diphenyl-1- picrylhydrazyl (DPPH) assay. Antiglycation activity was determined using inhibition of formation of advanced glycation end products (AGE), level of Nε-(carboxymethyl) lysine (CML), the level of fructosamine, and the formation of amyloid cross β-structure in bovine serum albumin after incubation with fructose. The protein oxidation was examined using the level of protein carbonyl content and thiol group. Results The present phytochemical analysis indicated that the flavonoid, total phenol, and condensed tannin contents in the extract were 71.73±2.48 mg quercetin equivalent/g of crude extract, 79.81±2.85 mg of gallic acid equivalent/ g of crude extract, 8.82±0.77 mg catechin equivalent/g of crude extract, respectively. The extract inhibited intestinal sucrase more than intestinal maltase with IC50 value of 1.47±0.19 mg/ml. It also slightly inhibited pancreatic α-amylase, pancreatic lipase and pancreatic cholesterol esterase. Oral administration of aqueous ethanol and n-butanol extract of Moringa stenopetala leaves (500 mg/kg body weight) and metformin (150mg/Kg) significantly reduced blood glucose level (P<0.05), significantly improved serum lipid profiles, liver enzymes and kidney functions in diabetic rats after 14 days. The extract also increased in size of islet of Langerhans in diabetic rats. Moringa stenopetala leaves significantly inhibited the formation of AGEs by approximately 54.75+0.94% at a concentration of 2mg/ml. Furthermore, Moringa stenopetala leaves extract reduced the levels of fructosamine, amyloid cross β-structure and Nε-(carboxymethyl) lysine (CML) . The leaves also prevented oxidative protein damage, including effects on protein carbonyl formation, thiol oxidation of BSA and antioxidant activity in DPPH assay Conclusion: The present results demonstrated the beneficial biochemical effects of Moringa stenopetala leaves extract by inhibiting intestinal α-glucosidase, pancreatic cholesterol esterase and pancreatic lipase activities. A daily supplement intake of the leaves of Moringa stenopetala may help in reducing diabetes induced glycation, hyperglycemia and hyperlipidemia. Keywords: Antihyperglycemic, Antihyperlipidemic, antiglycation, Moringa stenopetala, enzyme inhibitionItem Evaluation of ceftriaxone utilization in medical and emergency wards of Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia(Addis Ababa University, 2015-01) Sileshi, Alemayehu; Shibeshi, Workineh(PhD); Tenna, Admasu(PhD)Evaluation of ceftriaxone utilization in medical and emergency wards of Tikur Anbessa Specialized hospital By: Alemayehu Sileshi Addis Ababa University, 2015 Background: Ceftriaxone is one of the most commonly used antibiotics due to its high antibacterial potency, wide spectrum of activity and low potential for toxicity. The global trend shows misuse of this drug. Objective: This study was conducted to evaluate the appropriateness of ceftriaxone use in medical and emergency wards of Tikur Anbessa Specialized Hospital (TASH). Methods: A prospective cross-sectional study was conducted by reviewing medication records of 314 patients who received ceftriaxone during hospitalization at TASH between February 1 and June 30, 2014. Drug use evaluation (DUE) was conducted to determine whether ceftriaxone was being used appropriately based on six criteria namely indication for use, dose, frequency of administration, duration of treatment, drug-drug interaction (DDI) and culture and sensitivity (C&S) test. The evaluation was made as per the protocol currently developed. Additionally, areas which need intervention were identified and interventions were implemented. Results: The prescribing rate of ceftriaxone was found to be very high (58% point prevalence). Ceftriaxone use was empiric in 274 cases (87.3%) and specific in 5 cases (1.6%). The most common indication for ceftriaxone use was pneumonia; observed in 110 cases (35.0%). The most common daily dosage, frequency of administration and duration of treatment with ceftriaxone were 2g (88.9%), twice-daily (98.4%) and 8-14 days (46.2%), respectively. Inappropriate use of ceftriaxone was observed in most cases iv (87.9%), the greatest proportion of which was attributed to inappropriate frequency of administration (80.3%), followed by absence of C&S test (53.2%). Conclusions: This study revealed that the inappropriate use of ceftriaxone was very high in the medical and emergency wards of TASH. This may lead to emergence of resistant pathogens which in turn lead to treatment failure and increased cost of therapy. Therefore, adherence to current evidence-based guidelines is recommended. Key words: Ceftriaxone, drug use evaluation, antibiotic, rational use.