Pharmacognosy

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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 proteins
Post-marketing Quality Surveillance of Selected Antibacterial Agents Marketed in Setit Humera and west Gondar Zones, North West Ethiopia.
(Addis Ababa University, 2023) Denekew,Tewodros; Ashenef,Ayenew(Ass.Prof.); Eticha,Tadele(Ass.Prof.)
Background: The presence of low-quality medicines is becoming increasingly problematic in many parts of the world, particularly in developing countries. Antibiotics are among the most common anti-infective medicines that are falsified. Objective: The purpose of this study was to assess the quality of selected antibacterials that are marketed in Setit Humera and west Gondar Zones, North West Ethiopia. Methods: Seventy-one samples of the antibacterials were collected from six sites in Setit Humera and west Gondar Zones, North West Ethiopia. A mystery shopper collection system was used for sample collection. Visual inspection and confirmation of the registration status were carried out using the WHO/FIP/USP checklist and the EFDA's MRIS database, respectively. Then Pharmacopeial methods (USP, BP) were employed to assess the physicochemical parameters. Results: From 71 samples, 25.35% (18/71) were not registered and 15.49% (11/71) were registered but the license period was expired i.e not in line with the EFDA’s specification. Some (74.65% (53/71) observed samples) did not meet the visual inspection criteria outlined in the joint WHO/FIP/USP checklists. The physicochemical evaluation showed that all the samples studied met the quality specification with respect to the identification and hardness test. From 71 samples tested with regard to assay, dissolution, uniformity of dosage units, disintegration and friability tests, 27.49% (23/71), 16.9%, and 14.08% (10/71), 2.82% (2/71) and 8.57% (3/35) of samples were found to be substandard respectively. Overall, 56.33 % (40/71) of the samples tested were of poor-quality. Conclusion: The results indicated that some (56.33 %) antibacterial medicines circulating in the market did not meet the required quality. Therefore, the regulatory body (EFDA) should focus on enforcing the necessary measures to ensure that antibacterial drugs on the market meet the required mandatory standards
Quality Assessment of Antimicrobial Drugs: Amoxicillin Capsules, Amoxicillin + Clavulanate, Ciprofloxacin and Norfloxacin Tablets from Drug Retail Outlets of Selected Cities in Eastern Ethiopia.
(Addis Ababa University, 2023) Anjulo,Hailu; Ashenef,Ayenew (Assist. Prof.); Hymete,Ariaya(Prof.)
Rising incidence of substandard and falsified antimicrobial drugs is an increasing concern in developing nations. The beta-lactams and fluoroquinolones are among the broad-spectrum antimicrobial agents that are most frequently prescribed, inexpensive, and readily available in Ethiopia, for the treatment of infectious diseases. The consumption of substandard and/or falsified antimicrobial drugs has the potential to result in treatment failure, emergence and development of Antimicrobial resistance (AMR), and ultimately patient mortality. The objective of this study is to assess the quality of four commonly used antimicrobials (ciprofloxacin, norfloxacin, and amoxicillin and its combination with clavulanic acid) marketed in Dire Dawa and Jijiga cities, and Togo-Wuchale town with high potential for illegal drug trade in Ethiopia due to porous border through Somaliland. A total of 54 different brands/products of amoxicillin, amoxicillin plus clavulanic acid, ciprofloxacin, and norfloxacin formulations were collected covertly from 43 facilities using a convenience sampling strategy from March 16 to March 29, 2022, from the selected locations. The samples were first screened using GPHF-minilab protocol and then analyzed with references to USP and BP methods. The quality evaluation showed that 14.28% (6/42) of all samples failed the GPHF-minilab screening test quantitatively, 27.27% (6/22) of amoxicillin samples failed weight variation test, and 22.73% (5/22) of amoxicillin and 40% (2/5) of amoxicillin/clavulanate products failed to meet the assay test. Furthermore, 12.96% of the samples failed the dissolution test. Overall, 22.22% of the products analyzed did not meet pharmacopoeial specifications. Additionally, 56.25% of amoxicillin samples, 60% of amoxicillin/clavulanate, 20% of ciprofloxacin, and 54.54% of norfloxacin samples were found to be pharmaceutically inequivalent with their respective comparator products in relation to dissolution profile studies. The study had shown that the quality of essential antimicrobial medicines in eastern Ethiopia is substandard. This affirms the need for regular post-market surveillance to inform on the situation of antibiotic quality in eastern Ethiopia. Based on the accumulated evidence regulatory actions and mechanisms had to be also in place to circumvent the challenge
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 testing
Synthesis, Antibacterial Activity and Insilco Studies of 1-(2- ethyl acetate)-2-styryl 5-nitroimidazole Derivatives.
(Addia Ababa University, 2023-05) Aragaw,Misgana; Tadesse,Solomon(PhD); Bisrat,Daniel(PhD); Abebayehu,Mekonnen(PhD)
The proliferation of drug-resistant microorganisms that have acquired new resistance mechanisms contributes to the development of antimicrobial resistance. For more than 60 years, metronidazole (2) has served as an antibacterial and antiprotozoal agent. However, its prolonged usage has resulted in drug-resistance and associated with adverse effects. Metronidazole is usually not effective on Gram-negative and Gram- positive facultative anaerobic bacteria, which are considered as the most life- threatening pathogens. However, there are reports of metronidazole analogues with potent activity against the facultative anaerobic bacteria indicate that there is a different mode of action of metronidazole. As a result, it is important to synthesize new metronidazole analogs with unique mode of action in order to enhance the antibacterial efficacy of metronidazole while reducing toxicity. Recent studies have shown that the enzyme FabH (β-ketoacyl-acyl carrier protein synthase III), responsible for the first step of fatty acid biosynthesis (FAB), is a promising target for nitroimidazole derivatives that can be used as an effective anti-infective. In this study, we synthesized four 2-styryl 5-nitroimidazoles derivatives, via condensation of metronidazole with respective benzaldehydes and subsequent acetylation reactions. The chemical structures of the synthesized compounds were determined through 1H and 13C-NMR spectroscopy. We evaluated the antimicrobial activity of the synthesized compounds against six bacterial strains, three Gram- positive bacterial strains (S. aureus, S. epidermidus and S. agalactiae) and three Gram-negative bacterial strains (E. coli, P. aeruginosa and K. pneumoniae) using a two-fold serial dilution MTT assay. Of all the synthesized compounds, compound 33, ((E)-2-(5-nitro-2-styryl-1H-imidazol-1- yl)ethyl acetate) and 36, ((E)-2-(2-(4-(dimethylamino)styryl)-5-nitro-1H-imidazol-1- yl)ethyl acetate) equally demonstrated the most potent antibacterial activity against S. agalactiae (MIC = 1.56 μg/mL), P. aeruginosa (3.13 μg/mL), respectively. Additionally, compound 33 and 36 also exhibited potent activity against K. pneumonia, with an MIC value of 6.25 μg/mL and 12.5 μg/mL, respectively. Molecular docking studies revealed that both compounds have favorable hydrophobic and electrostatic interactions with conserved residues in the binding site of E. coli FabH -CoA complex (1HNJ.pdb). Overall acetylation of 2-styryl-5-nitroimidazoles improved both their biological activity and binding interaction with the target protein.
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,Hiwot
Globally, 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 cancer
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.
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, Solomon
The 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.
In Vivo Anti-malarial Activities of the Solvent Fractions of the Roots of Euphorbia Abyssinica J.F.Gmel (Euphorbiaceae) against Plasmodium Berghei Infection in Mice
(Addis Abeba univerisity, 2022-05) Fikadu, Muluemebet; Umer, Shemsu
Despite all the advances in the health care system, malaria remains a devastating problem in subSaharan Africa. Moreover, resistance to the existing pharmacological agents is the major factor overrating the issue. Therefore, researches to discover newer antimalarial agents having better safety and efficacy are being held. Natural products particularly medicinal plants that are known sources of new drugs and/or lead compounds provide potential options. The root of Euphorbia abyssinica (Euphorbiaceae) is used to treat malaria in some parts of Ethiopia traditionally and the anti-malarial activity of the 80% hydroalcoholic crude extract of the roots has shown a very good antimalarial activity. However, no bioassay-guided fractionation study is conducted yet. Thus, the current study investigated, the anti-plasmodial activities of solvent fractions of the roots of E. abyssinica in mice infected with Plasmodium berghei using the four-day suppressive test. The antimalarial activities of ethyl acetate, methanol, and aqueous fractions of the crude extract of the roots of the plant were evaluated using parameters like; % parasitemia, mean survival time, body weight, rectal temperature and packed cell volume at doses of 100, 200 and 400 mg/kg/day administered orally. Windows SPSS version 25 was used for data analysis. One-way Analysis of variance (ANOVA) followed by Tukey's post hoc test was used to compare data between groups. All the three fractions tested exerted dose-dependent chemosupressive activity. The ethyl acetate fraction showed superior parasite suppression (78.87%) at the highest dose (400 mg/kg/day). The 100 and 200 mg/kg/day doses were also able to produce parasite suppression of 52.43% and 69.57%, respectively. Besides, all the three dose levels of ethyl acetate fraction produced a statistically significant mean survival time (MST) prolongation (p<0.001) as compared to the negative control. The methanol fraction also displayed parasite suppression of 50.49 and 68.50 % at 200 and 400 mg/kg/day, respectively. Likewise, at both doses, it prolonged MST significantly (p<0.001). However, the aqueous fraction exhibited weaker chemosupressive activity (43.92%) V and a statistically significant (p<0.001) prolongation in MST only at the dose of 400 mg/kg/day. A statistically significant (p<0.001) prevention of reduction in packed cell volume (PCV) was observed in mice treated with the ethyl acetate fraction at 200 and 400 mg/kg/day. Nevertheless, the methanol and the aqueous fractions failed to prevent reduction in PCV significantly. Except for the larger dose level of ethyl acetate fraction (p<0.001), all the dose levels of the three fractions failed to prevent a drop in temperature. Similarly, only the larger dose level of the methanol fraction prevented weight loss (p<0.001). From this study, it can be concluded that all three fractions showed promising antimalarial activity. The ethyl acetate fraction displayed a very good antiplasmodial activity. The finding of this study supports its traditional use and the previous study conducted on the crude extract of the plant. Thus, there is a need for further studies on the plant including evaluation of prophylactic activity and isolation of compounds responsible for bioactivity, particularly from the ethyl acetate fraction.
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, Epbrem
Perinatal 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 (Samatsinewy
In vivo Antimalarial Activity of the Hydroalcoholic Extract of Rhizomes of Kniphofia foliosa Hochst and Kniphofia insignis Rendle and their Constituents
(Addis Abeba University, 2021-03) Alebachew, Yonatan; Asres, Kaleab(Professor); Dr.Bisrat, Daniel
Malaria is a major public health problem that affects millions of people. The widespread emergence of antimalarial drug-resistant Plasmodium strains especially the recent emergence of artemisinin resistance poses a great challenge in future prevention and control of malaria. As a result, there is an urgent need to discover new, safe, and effective antimalarial drugs with novel mechanisms of action. In this regard, traditional medicinal plants have paramount importance as seen in the discovery of the forefront antimalarials. Kniphofia foliosa Hochst and Kniphofia insignis Rendle are endemic Ethiopian plants traditionally used to treat malaria in different parts of the country. In the present study the 80% methanol rhizome extracts of both plants and some of their constituents were investigated for their antimalarial activity. Fractionation of the hydroalcoholic extract of K. foliosa followed by preparative thin layer chromatography (PTLC) led to the isolation knipholone, dianellin, 10-knipholone gentibioside and 12-hydroxypentadec-9-en-1-yl methyl phthalate (HPMP) identified on the basis of spectroscopic (ESI-MS, 1D and 2D-NMR) data. Similarly, knipholone was isolated for the first time from crude phenolic fraction of K. insignis. The hydroalcoholic extracts of both plants, the phenolic fractions from K. foliosa and the compounds isolated thereof showed in vivo antiplasmodial activity (p<0.001) in Peters‘ 4-day suppressive test against P. berghi infected Swiss albino mice. Particularly, the hydroalcoholic extract of K. foliosa (400 mg/kg), 10- knipholone gentibioside (100 mg/kg) and knipholone (200 mg/kg) showed the highest activity with chemosuppression values of 61.52, 79.00 and 60.16%, respectively. From the dose-response plot, the median effective (ED 50 ) doses of 10-knipholone gentibioside, knipholone and dianellin were determined to be 29.04, 81.25 and 92.31 mg/kg, respectively. Molecular docking study revealed that knipholone had a strong binding affinity to Plasmodium falciparum l-lactate dehydrogenase (pfLDH) target. Results of the current study showed that the extracts and compounds of the plants possess genuine in vivo antimalarial effect against P. berghei in mice, supporting their traditional use for the treatment of malaria.
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, Solomon
Lobelia 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.
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. values
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, Daniel
Diarrhea 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.
Antiproliferative Activities of Alkaloids from Crinum abyscinicum Hochst. ExA. Rich Bulb Extract
(Addis Abeba University, 2019-08) Abebe, Besufekad; Prof.Hymete, Ariaya; Dr.Bisrat, Daniel
Cancers 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.
Evaluation of the in vitro acaricidal properties of the latex and major compounds isolated from the leaves of aloe yavellana (reynolds) against amblyomma variegatum (ixodidae ticks)
(Addis Ababa Universty, 2017-12) Hailesillassie, Tibebu; Eguale, Tadesse (PhD)
Evaluation of the in vitro acaricidal properties of the latex and major compounds isolated from the leaves of Aloe yavellana (Reynolds) against Amblyomma variegatum (ixodidae ticks). Tibebu Hailesillassie Addis Ababa University, 2017 Aloe yavellana Reynolds is endemic to Ethiopia where its leaf latex is traditionally used for the treatment of various illnesses of humans and domestic animals in Yabelo town and other pastoralist areas of south western part of the country. The latex and isolated compounds were assessed for their acaricidal activities against Amblyomma varigatum tick larvae by using larval packet test (LPT). At a concentration of 50 mg/ml, the leaf latex showed acaricidal activity 24 h post exposure, with percentage mortality (E %) of 62.50%. Phytochemical investigation of the leaf latex led to the isolation of two anthrones, identified as microdontin A/B and aloin A/B by means of spectroscopic techniques including ESI-MS, 1H, 13C NMR and DEPT spectral data. Among the isolated compounds, microdontin A/B showed E% of 30.83 at a dose of 50 mg/ml. EC50 and EC99 values of the latex, microdontin A/B and aloin A/B were estimated to be 35.82 and 83.48 mg/ml; 89.40 and 196.49 mg/ml; 257.69 and 585.98 mg/ml, respectively. On the basis of the above results the latex was found to be more effective in killing larvae ticks than the individual isolated compounds. Dose response data of the latex, microdontin A/B and aloin A/B indicated the gradual increase in mortality pattern with slopes and R2 values of 1.047 and 0.909; 0.459 and 0.946; 0.164 and 0.988, respectively. In conclusion, the leaf latex of A. yavellana and its isolated compounds could have the potential to be used as bioacaricides against ticks and tick born disease (TBDs).
Hypoglycemic and antihyperglycemic effect of leaves extracts of Psidium guajava in normoglycemic and streptozotocin-induced diabetic mice
(Addis Ababa University, 2015-06) Godebo, Amanuel; Mekonnen, Negussu(PhD); Makonnen, Eyasu (PhD)
Background: Diabetes mellitus is a metabolic disorder of multiple etiologies characterized by chronic hyperglycemia. As the morbidity and mortality rate from diabetes is increasing in low- and middle-income countries, it is necessary to evaluate medicinal plants for their pharmacological effects to support existing drugs in treating diabetes. The present study was undertaken to evaluate the hypoglycemic and antihyperglycemic activity of leaf extracts of Psidium guajava in normoglycemic and streptozotocin-induced diabetic mice. Methods: The aqueous and ethanol extracts of Psidium guajava leaves were prepared. Swiss albino mice of either sex weighing 20-30 grams were selected for the experiments. Normal mice were grouped into eight groups to carry out hypoglycemic effect of the extracts, whereas mice that were made diabetic were grouped into nine groups to study the antihyperglycemic effect of the extracts. Diabetes was induced by Streprozotocin (STZ). Blood glucose levels were measured using glucose oxidase method. Results: The aqueous and ethanol extracts of Psidium guajava leaves lack hypoglycemic effect on normoglycemic mice. However, a significant decrease in blood glucose levels (P<0.05) was observed after administering for 21 days treatment of the aqueous and ethanolic extracts of Psidium guajava leaf to Streptozotocin-induced diabetic mice. Guava leaf extracts contain alkaloids, phenols, flavonoids, tannins and saponins that could be responsible for the observed antihyperglycemic effect. It was also observed that the extracts have shown no acute toxicity. Conclusion: The aqueous and ethanol extracts of Psidium guajava leaves are effective in lowering blood glucose level in diabetic mice, but lack hypoglycemic effect in normoglycemic mice. Further studies are warranted to elucidate possible mechanism(s) of action of the plant material. Key words: Hypoglycemic, Antihyperglycemic, Psidium guajava, Strepotozotocin, Mice.
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 Acknowledgments
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 inhibition
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.

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