Pharmacology

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Evaluation of Anti-Inflammatory and Wound Healing Activities of the 80% Methanol Fruit Extracts Of Dovyalis Abyssinica A. Rich. in Mice
(Addis Ababa University, 2011-10) Abdissa, Hailu; Engidawork, Ephrem (PhD); Asres, Kaleab(PhD)
Dovyalis abyssinica locally known as “Koshim” is traditionally used to treat conditions such as hemorrhoids, ulcers and swelling of the throat. The toothbrush sticks are also reported to be used for oral hygiene. There is also a traditional claim that the fruits of D. abyssinica promote wound healing. However, there is no scientific evidence that justifies the traditional claims and therefore the present study was aimed at evaluating the wound healing and anti-inflammatory effects of the fruits wound healing mice models. In this study, the fruits of D. abyssinica were evaluated by formulating the 80% methanol fruit extracts in simple ointment base in strengths of 5% and 10% for topical applications for excision as well as incision wound models. Extract solutions in saline in strengths of 100 mg, 200 mg and 400 mg/Kg body weight doses were also prepared and used for oral administration for antiinflammatory activity tests. From the excision wound model, rate of wound contraction, epithelization period and hydroxyproline content were determined. From the incision wound model, tensile strength of the healing wound was evaluated. For the evaluation of the antiinflammatory activity, carrageenen-induced hind paw edema model was employed and increase in paw size and % inhibition of edema were determined. The 80% methanol fruit extracts exhibited a significant wound healing activity in both strengths compared with control as evidenced by an increase in % wound contraction (p < 0.001), a decrease in epithelization period (p < 0.001), and an increase in hydroxyproline content (p < 0.001) in excision wound model. In the same model, the 10% extract ointment resulted in a significant wound contraction at days 8, 12 and 16 and hydroxyproline content compared against both standard and 5% extract ointment (p < 0.01). In the incision wound model, both 5% and 10% extract ointments resulted in a significant increase in tensile strength compared with control (p < 0.001). The same extract also exhibited a significant anti-inflammatory effect compared with control particularly 3 to 5 h after extract administration as shown by a decrease in edema expressed as % reduction of edema. At the 3rd h, both 200 and 400 mg/kg body weight doses exhibited a higher effect compared against control (p < 0.001) while the 100 mg/kg extract dose resulted in a comparable effect compared with same (p < 0.01). At the 4th and 5th h, all the extract doses exhibited a significant effect compared with control (p < 0.001). It was also shown that the viii 400 mg/kg extract dose exhibited a significant effect compared with the 100 mg/kg extract dose (p < 0.05 at the 3rd and 5th h and p < 0.01 at the 4th h). The 80% extract of the fruits of Dovyalis abyssinica, therefore, proves to support healing of wounds as the traditional claims as evidenced by an increase in wound contraction, hydroxyproline content and tensile strength and a decrease in epithelization period compared with control results. It also possesses a significant anti-inflammatory effect as shown by a significant decrease in edema compared with control results supporting the wound healing effect.
In-vivo Anti-inflammatory Activity of the Leaf Extracts and Fractions of Ocimum Suave in Mice Model
(Addis Abeba University, 2011-10) Masresha, Birhanetensay; Prof.Makonnen, Eyasu; Dr. Debella, Asfaw
Ocimum suave has been used in Ethiopian traditional medicine to relieve pain, fever, inflammation and possibly other diseases conditions. Although there are some reports on analgesic, antipyretic, antiulcer, antimicrobial and wound healing effects, no study has been made regarding their possible anti-inflammatory effect. The objective of the present study was, therefore, to investigate ethanol and aqueous extracts and fractions (butanol and water residue) of the aqueous extract of the plant material. The ethanol and aqueous extract were screened for their anti-inflammatory activities on carrageenan-induced mouse paw edema at three dose levels 400, 600 and 800mg/Kg. The butanol and water fractions of the aqueous extract were also investigated for their anti-inflammatory activities on carrageenan, histamine and serotonin-induced mouse paw edema at three dose levels 50, 100, 200mg/Kg. Normal saline and aspirin (200mg/Kg) were employed as negative and positive control groups, respectively. Both ethanol and aqueous extracts significantly decreased carrageenan-induced inflammation at all doses used. Greater paw edema inhibition was, however, observed by the aqueous extract than ethanol one at 600 and 800mg/Kg dose levels. Similarly, both butanol and water fractions also showed significant reduction of inflammation induced by carrageenan, histamine and serotonin in mice paw. Highest inhibition, however, was exhibited by the aqueous fraction at 100mg/Kg and 200mg/Kg dose levels. From the present findings, it can be concluded that the extracts and fractions of the plant material have got anti-inflammatory properties. Thus the results support the traditional use of this plant in inflammatory conditions. Further investigation, however, should be pursued to identify the exact mechanism (s), isolate the bioactive principle (s) responsible for the anti-inflammatory action and others.
Evaluation of Renoprotective Effects of Euclea Divinorum Hierns Against Gentamicininduced Nephrotoxicity in Rats
(Addis Ababa University, 2011-10) Feyissa, Tadiwos; Engidawork, Ephrem (PhD); Asres, Kaleab(PhD)
Despite their nephrotoxicity and ototoxicity, aminoglycoside antibiotics (such as gentamicin and amikacin) are still considered to be important agents against lifethreatening infections owing to their bactericidal efficacy, synergism with ß-lactam agents, low cost, limited bacterial resistance and a post-antibiotic effect. The goal of reducing or protecting against their nephrotoxicity will increase the safety of the drugs and significantly improve the quality of life of patients taking aminoglycosides. In this study, the renoprotective effects of the crude extract and solvent fractions of Euclea divinorum H. leaves was evaluated against gentamicin-induced nephrotoxicity in rats as the dried roots of the plant is crushed and swallowed for some kidney problems in some regions of Ethiopia. For the assessment of gentamicin nephrotoxicity biochemical and morphologic parameters were measured. Rats were divided into seven experimental groups of 6 (three male and three female) each. The first group served as a control (CON, group I) and given vehicle (Tween 80, 2%, v/v) in water orally. The second group (GEN, group II) were treated with normal saline intraperitonally for two days and afterwards gentamicin (100 mg/kg/day) for eight days. The rest of the groups received crude extract at three different doses 200 mg/kg (C200, group III), 150 mg/kg (C150, group IV) and 100 mg/kg (C100, group V), methanol fraction (M100, group VI) and aqueous fraction (W100, group VII) of E. divinorum orally for two days before and eight days concomitantly with gentamicin (100 mg/kg/day, intraperitonally). Gentamicin produced changes in renal indices, including increase in blood urea nitrogen (BUN) (111.46%, p<0.001) and creatinine (183.26%, p<0.001) levels compared to CON. Moreover, it also caused alterations in redox parameters such as increase in lipid peroxidation (83.89%, p<0.01) and decrease in catalase (CAT) activity (81.8%, p<0.05), superoxide dismutase (SOD) activity (40.3%, p<0.01) and glutathione (GSH) levels (38.06%, p<0.01) when compared to CON. Morphologic pathologic analysis also revealed a decrease in body weight (p<0.001), an increase in normalized kidney weight (42.34%, p<0.001) and more extensive/marked tubular necrosis, inflammation, hyaline vi ii casts in tubular lumen, hydropic degeneration and disintegrated nucleus in GEN group compared to CON. Pre- and co-treatment with the crude extract and solvent fractions E. divinorum leaves reversed alterations caused by gentamicin as evidenced by decrease in normalized kidney weight (p<0.05 in C150, C100 and W100; p<0.001 in M100), BUN (p<0.05 in C200; p<0.001 in C150, C100, M100 and W100), serum creatinine (p<0.05 in C200; p<0.01 in C150; p<0.001 in C100, M100 and W100), lipid peroxidation (p<0.05 in all cases) and increase in body weight (p<0.05 in C200 and C150; p<0.01 in C100, M100 and W100), CAT activity (p<0.05 in C200 and C150; p<0.01 in W100; p<0.001 in C100 and M100), SOD activity (p<0.05 in C200, C150, C100 and W100; p<0.01 in M100) and GSH level (p<0.05 in all cases). Further, crude extract and solvent fractions of the plant were observed to mitigate the histological renal changes associated gentamicin. Based on the study findings, it could be concluded that gentamicin induces generation of free radicals leading to oxidative damage to kidneys and acute renal failure. E. divinorum might act in the kidney as a potent scavenger of free radicals to prevent the toxic effects of gentamicin with a maximal nephroprotection by the methanol fraction followed by aqueous fraction and then by crude extract. In conclusion, E. divinorum might be a potential protective agent against drugs-induced nephrotoxicity besides its traditional uses. Key terms: gentamicin, gentamicin-induced nephrotoxicity, nephroprotection, Euclea divinorum, Dedeho and Mi'essa.
Synthesis, Antimalarial and Antileishmanial Evaluation of Some Quinazoline Derivatives
(Addis Ababa University, 2012-01) Simegniew, Yihenew; A. Bekhit, Adnan
Malaria and leishmaniasis are neglected tropical parasitic diseases affecting billons of people around the globe. Owing to their promising antimalarial and antileishmanial activities, seven novel 2-(substitutedstyryl)-3-aryl-4(3H)-quinazolinones were synthesized in good yields (65.2-86.4%) by using cyclization and condensation reactions. Structures for the synthesized compounds were determined using elemental microanalysis, IR, 1H NMR and 13C NMR (for compound IVb). The in vivo antimalarial and the in vitro antileishmanial activities of the synthesized compounds were evaluated using mice infected with P. berghi ANKA strain and L. donovani strain, respectively. The target compounds showed poor antimalarial activities with percent suppression of 29.10-44.39% which was not significantly different from the negative control group (P>0.05). All the synthesized compounds displayed superior antileishmanial activities (IC50 values, 0.0128-3.1085 μg/ml) as compared to the standard drug miltefosine (IC50 = 3.1911 μg/ml). (E)-2-(4-chlorostyryl)-3-p-tolyl-4(3H)-quinazolinone (IVb) is the compound with promising antileishmanial activities (IC50 = 0.0128 μg/ml) which is approximately 4 and 250 times more active than the standard drugs amphotericin B deoxycholate (IC50 = 0.0460 μg/ml) and miltefosine (IC50 = 3.1911 μg/ml), respectively. Key words: Quinazolines, Antimalarial activities, Antileishmanial activities.
Renal Effects of Crude Khat (Catha Edulis F.) Extract when Administered alone and Concomitantly with Gentamicin in Rats
(Addis Ababa University, 2012-08) Shewamene, Zewdneh; Engidawork, Ephrem(PhD)
Khat use has been reported to produce significant acute and chronic toxic effects including oxidative damage of cellular macromolecules such as DNA, lipids and proteins contributing to the development of several pathologies, notably cancer, nephrotoxicity, hepatotoxicity and neurodegenerative diseases. Although various studies have been carried out on the pharmacological actions; the effect of khat induced changes in the redox status of kidney and other tissues has not yet been worked out in details. The aim of this study was therefore to investigate whether khat has a direct or permissive role in causing nephrotoxicity. Sixty four healthy Sprague Dawely rats were divided into eight experimental groups of eight animals and khat was administered in different doses (100 mg/kg, 200 mg/kg and 400 mg/kg orally) for ten days alone and two days before and eight days in combination with gentamicin (100 mg/kg, intraperitoneally). Following administration, animals were killed by light ether anesthesia and blood and renal tissue were used to measure renal markers, including creatinine, blood urea nitrogen, antioxidant enzymes as well as markers for lipid peroxidation using established protocols. Administration of khat at high dose (400 mg/kg) significantly caused marked renal dysfunction as evidenced by increased serum creatinine (p<0.001), blood urea nitrogen (p<0.001), and lipid peroxidation (P<0.001), whereas renal superoxide dismutase and catalase enzymatic activities were decreased (p<0.001) compared to control animals. Furthermore, disturbed renal indices by gentamicin were considerably accentuated by high dose (400 mg/kg) of crude khat extract when given concurrently with gentamicin. Khat alone or with gentamicin was also found to alter renal histopathology, normalized kidney weight and body weight of rats with increasing dose. In conclusion, khat at high dose alone or with gentamicin is able to induce renotoxicity in rats. Key words: creatinine, blood urea nitrogen, superoxide dismutase, catalase, khat, rat
Evaluations of the Effect of Subchronic Administration of Crude Khat Extract (Catha Edulis F.) on Learning and Memory in Mice
(Addis Ababa University, 2014-01) Mohammed, Faiz; Engidawork, Ephrem (PhD); Nedi, Teshome (PhD)
Learning may be defined as the ability to alter behavior based on experience. If there is no learning, there can be no memory later. Memory is the ability of an individual to record sensory stimuli; events, information, etc. and retain them over short or long periods and recall the same later when needed. People chew khat believing that it improves memory, make them alert and think clearly. This study was made to add to the existing body of knowledge about khat and memory. To this effect, 36 albino mice, 6-8 weeks old, were administered orally with a single daily dose of khat extract for 30 days. The animals were divided into four groups. The first group served as controls and was administered with 0.5 ml 3% Tween 80 in water. Group two (K100), three (K200) and four (K300) were administered 100, 200 and 300 mg/kg khat extract, respectively. The animals were then subjected to Multiple T maze (MTM) and Morris water maze (MWM) task performance. The result showed that subchronic administration of crude khat extract at doses used did not have a significant effect on learning using the two models. K200 (p< 0.01) and K300 (p< 0.001) significantly impaired short-term memory in both models, while K100 impaired STM in MWM but not in MTM. Khat at all doses used did not have any significant effect on long-term memory using both models. Crude khat extract administration also had initially anorexic effect but this was followed by development of tolerance. The results collectively showed that subchronic exposure of mice to khat could alter formation of short-term memory, without affecting learning and long-term memory. II Key Words: Catha edulis, learning, memory, short-term memory, long-term memory, Morris water maze task, Multiple T maze task.
In Vitro and In Vivo Anti-trypanosomal Activity of Dichloromethane and Methanol Crude Leaf Extracts of Dovyalis abyssinica (Flacourtiaceae) against Trypanosoma congolense Field Isolate
(Addis Ababa University, 2014-01) Tadesse, Belay; Shibeshi, Workineh(PhD); Terefe, Getachew(PhD)
African Trypanosomosis is a neglected tropical disease of medical and veterinary importance. Parasite control relies on the use of few drugs whose resistance and unacceptable toxicities urged the investigation of new agents, preferably from natural sources. Though Dovyalis abyssinica has been reported to posses significant trypanocidal activity on Trypanosoma brucei in in vitro model, activity on trypanosome infected laboratory animals has not yet been worked out. The aim of the present study was, therefore, to investigate the in vitro and in vivo activity of D. abyssinica on T. congolense field isolate. To evaluate the effect on motility, 200 μl T. congolense infected blood was mixed with 50 μl of 20, 10, 2, 0.1, 0.015 mg/ml dichloromethane and methanol extracts. Reduction or cessation of motility was then microscopically monitored for 120 minutes, and the remaining in vitro mixtures were inoculated to healthy mice and monitored for development of infection for 21 days. Furthermore, fifty T. congolense infected mice were randomly grouped into ten groups of five and administered with curative doses (250, 200, 150 and 100 mg/kg) of dichloromethane and methanol and 28 mg/kg diminazene aceturate and dimethylsulfoxide. Following administration, parasitemia, packed cell volume (PCV), rectal temperature, body weight and survival time were iii monitored. Suppressive doses of the extracts (250 and 200 mg/kg) were administered 24 hours post-infection and parasitemia was monitored. Dichloromethane and methanol extracts at 20, 10, 2 mg/ml concentrations ceased parasite motility within one hour and eliminated subsequent infectivity in mice for 21 days. Administration of dichloromethane and methanol extracts at 250 and 200 mg/kg reduced (p<0.05) parasitemia and rectal temperature, and improved (p<0.05) PCV, mean body weight, and mean survival time compared to DMSO treatment. In conclusion, D. abyssinica at higher concentrations in vitro and higher curative doses in vivo in mice posses anti-trypanosomal activity. Keywords: Anti-trypanosomal, D. abyssinica, in vitro, in vivo, T. congolense, mice.
Evaluation of in Vitro and in Vivo Antitrypanosomal Activity of Aqueous and Methanol Leaf Extracts of Clutia Abyssinica (Euphorbiaceae) and Verbascum Sinaiticum (Scrophulariaceae) Against Trypanosoma Congolense Field Isolate
(Addis Ababa University, 2014-01) Mergia, Ermias
Aqueous and methanol leaf extracts of C. abyssinica and V. sinaiticum were investigated for the presence of secondary metabolites, their in vitro and in vivo activity against Trypanosoma congolence, the main causative agent of African animal trypanosomosis in Sub-Saharan Africa and Ethiopia. The in vitro assay was carried out by monitoring test concentrations of 4, 2, 1, 0.4 and 0.2 mg/ml for cessation or reduction in motility of trypanosomes followed by monitoring for loss of infectivity to mice. The in vivo antitrypanosomal efficacy of the extracts was evaluated in Swiss albino mice infected with T. congolense field isolate. The leaf extracts were administered 12 days post-infection at peak parasitaemia level of ~108 trypanosomes/ml at doses of 100, 200 and 400 mg/kg by intraperitoneal injection once daily for 7 days. Parasitaemia, packed cell volume (PCV), mean survival time and change in body weight were used as indices for monitoring the efficacy of the extracts by comparing with the positive control: 28 mg/kg dose of diminazene aceturate and negative control: 2% tween 80 treated groups. Phytochemical screening revealed presence of alkaloids, anthraquinones, flavonoids, glycosides, phenolic compounds, saponins, steroids, terpenes and tannins. An appreciable in vitro activity was attained by the methanol extract of C. abyssinica at 4 mg/ml concentration which ceased motility of trypanosomes within 30 min and which caused loss of infectivity of trypanosomes to mice, which remained aparasitaemic for 21 days after the inoculation of the in vitro mixtures. The extracts had a lethal dose greater than 2000 mg/kg and there were no evidences of acute toxicity at the doses tested. Highly significant (p<0.001) reduction in pre-treatment parasitaemia by 3.91% (7.38+0.18) and increase in PCV by 1.12% (48.66+0.20) was noticed in animals treated by the methanol leaf extract of C. abyssinica at dose of 400 mg/kg; while body weight improvement by 1.67% (22.54+0.28) and mean survival time of 40.20 ± 0.37 days was seen in the group treated by 400 mg/kg methanol leaf extract of V. sinaiticum. In general, the results obtained suggest ethno-pharmacological usefulness of these plants and necessitate further studies to be carried on isolated active substances from these plants. Key words: Trypanosomosis, Trypanosoma congolense, Clutia abyssinica, Verbascum sinaiticum, Parasitaemia, Packed cell volume, Body weight, Mean survival time
In Vivo Antimalarial Activity of Solvent Fractions of the Leaf of Justicia Schimperiana Hochst. Ex Nees (Acanthaceae) Against Plasmodium Berghei in Mice
(Addis Ababa University, 2014-02) Abdela, Jemal; Shibeshi, Workineh(PhD); Engidawork, Ephrem (PhD)
In spite of tremendous reduction in malaria-associated morbidity and mortality achieved during the last decade, malaria still remains a major global public health problem accounting for about 219 million infections and 0.66 million deaths in 106 malaria-endemic countries in the year 2010. Increasing resistance of Plasmodium falciparum to almost all the available antimalarial drugs urged a search for newer antimalarial drugs. Justicia schimperiana is traditionally used for the treatment of malaria and a study conducted previously on the crude extract confirmed that the plant is endowed with antimalarial activity. The present study was therefore aimed to evaluate antimalarial activities of chloroform, methanol and aqueous fractions of the leaves of Justicia schimperiana against Plasmodium berghei in mice. To this effect, following successive soxhlet extraction and maceration, the resulting fractions were evaluated at doses of 200 mg/kg, 400 mg/kg and 600 mg/kg using the 4-day suppressive, curative and prophylactic tests. All the three fractions had shown significant suppression of parasitemia in the 4-day suppressive test, of which the methanol fraction exerted the highest chemosuppression (65.2%, p<0.001) at 600 mg/kg followed by the aqueous fraction (40.93%, p<0.001) at iv the same dose. The methanol fraction also showed significant suppression of parasitemia in both curative (67.44%, p< 0.001) and prophylactic (35.02%, p<0.01) tests at 600 mg/kg. Furthermore, all doses of the methanol fraction significantly (p<0.05) prevented the reduction in rectal temperature in the 4-day suppressive, curative and repository tests. Therefore, the high antimalarial activity observed in methanol and aqueous fraction indicates the active constituents of the plant are semi-polar and polar in nature. Key words: Justicia schimperiana, in vivo, anti-malarial activity, Plasmodium berghe
Evaluation of In Vivo Antihypertensive and Ex Vivo V asodepressor Activities of the Seed Extract of Calpurnia aurea (Ait.) Benth.subsp. aurea (Fabaceae)
(Addis Ababa University, 2014-03) Getiye, Yohannes; Engidawork, Ephrem (PhD); Tolessa, Tesfaye
Being the most important modifiable risk factor for stroke, renal, vascular and heart diseases; hypertension is still one of the leading causes of disability, morbidity and mortality among the populace worldwide. Consequently, the continued search for alternative antihypertensive agents of natural origin, with fewer side effects but greater effectiveness, necessitated evaluation of Calpurnia aurea for possible antihypertensive potential. In this study, the antihypertensive property of hydro-alcoholic seed extract of Calpurnia aurea was assessed using in vivo and ex vivo techniques. The in vivo antihypertensive efficacy of the crude extracts was evaluated in normotensive and 2K1C rat model of hypertension. The crude extract caused a significant fall in systolic blood pressure (SBP), diastolic blood pressure (DBP)and mean arterial blood pressure (MABP) at the doses of 15, 30 and 45 mg/kg in normotensive anaesthetized rats (p < 0.05, p < 0.01, p< 0.001).The effect on DBP was greater than SBP. In the same manner with the normotensive study, the BP fell dose-dependently and significantly in renal hypertensive rats, induced by renal ischemia. The extract produced 15.4% (p< 0.05), 26.9% (p< 0.01), 33.2% (p <0.01) reduction in SBP at the respective doses of 15, 30 and 45 mg/kg. Similar to the normotensive result, higher DBP effect was observed; 15.1% (p< 0.05), 30.2% (p< 0.01), 36.1% (p <0.01) fall from the control value at the above mentioned doses. Regarding MABP; 15.2% (p< 0.05), 28.8% (p <0.01) and 34.9% (p <0.01) reduction was noted with 15 mg/kg, 30 mg/kg and 45 mg/kg doses of the extract, respectively. The extract also caused a dose-dependent relaxation of guinea pig aorta precontracted with KCl (80mM),at a concentration of 5–250 mg/mL, with a maximum relaxation of 92.1±0.72% (p < 0.001) achieved at 250 mg/mL concentration. The relaxation mechanism was found to be independent of the endothelium system, muscarinic iv receptors, histamine receptors, ATP dependent K+ channels, cyclooxygenase enzymes and cGMP/NO pathway. The relaxation may be correlated with the effect on calcium ion channels, as it shifted the Ca2+ dose response curve (p< 0.05, p< 0.01 and p< 0.001) to the right with suppression of the maximum effect by 37.4% (p < 0.001). In conclusion, the findings suggest that the extract had a promising antihypertensive effect most likely caused by dilation of the blood vessels through Ca++ channel blockade, a confirmation for the folkloric use of the plant. Key words: Hypertension, Calpurnia aurea, hydro-alcoholic seed extract, in vivo, ex vivo, antihypertensive, vasorelaxation.
Evaluation of in vivo Anti-diarrheal Activity of 80%Methanolic Extract of the Leaves of Croton macrostachys Hochst. (Euphorbiaceae) in Rats
(Addis Ababa University, 2014-03) Bussa, Zebenay; Engidawork, Ephrem (PhD); Nedi, Teshome (PhD)
Diarrhea is a common cause of death in developing countries. It is also one of the primary causes of morbidity and mortality on a global scale, leading to 1 billion disease episodes and 1.8 million deaths each year, among children under five years of age. Due to limitations associated with various treatments available, the need for developing newer drugs is imperative. This study aimed at investigating the in vivo anti-diarrheal activity of 80% methanolic extract of leaves from the traditionally used medicinal plant, named Croton macrostachys. The effect of the 80% methanolic extract in rodents on castor oil-induced diarrhea, intestinal transit, and enteropooling was evaluated at doses of 200, 400, and 600 mg/kg body weight. The anti-diarrheal index (ADI) was calculated combining all diarrhea indicators to see the relative effect of the extract. In castor oil induced diarrhea, the extract produced a significant (p < 0.001) reduction in the severity and frequency of diarrhea, and significantly delayed onset of diarrhea at all doses tested. It was equally effective to that of loperamide in this model at 600 mg/kg by providing 100 % protection against diarrhea. In the castor oil induced intestinal transit test, the extract produced a significant (p < 0.01) decrease in propulsion with peristaltic index (PI) values of 40.03 ± 3.00 and 39.48 ± 2.27, respectively at doses of 400 and 600 mg/kg versus 56.38 ± 1.76 % for control. However, the effect was not significant at 200 mg/kg. The extract also showed a significant reduction in weight and volume of intestinal fluid accumulation, at doses iv of 200, 400, and 600 mg/kg. The highest ADI was obtained with the dose of 600 mg/kg of the extract, which was comparable to that produced by the standard. In conclusion, the results obtained showed that 80% methanolic extract of the leaves of Croton macrostachys contain some biologically active principles that are active against diarrhea, and this may be the basis for its traditional use for treating diarrhea. Therefore, it is a good candidate for further fractionation of the extract and study. Key Words: Croton macrostachys, Castor Oil, Anti-diarrheal Activity, Loperamide, Atropine, Anti-diarrheal index
In-vivo Anti-inflammatory Effect of the Roots of Indigofera spicata Forssk in Mice
(Addis Ababa University, 2014-04) Seid, Jibril; Engidawork, Ephrem (PhD); Nedi, Teshome (PhD)
The search for new anti-inflammatory agents from the huge array of medicinal plant resources is intensifying because currently available anti-inflammatory drugs pose a major problem including induction of gastric or intestinal ulcers as well as cardiovascular side effects during their clinical use. A previous study indicated that the aqueous and methanol extracts of the root of the I. spicata possessed anti-inflammatory and analgesic activity. In an effort to further the research, the present study was aimed to investigate the anti-inflammatory effects of chloroform, absolute methanol and aqueous fractions of the roots of the plant. To this effect, different doses of the fractions (50,100 and 200 mg/kg) were investigated for anti-inflammatory activity using acute (carrageenan induced mouse paw edema) and sub acute (formalin induced mouse paw edema) model of inflammation. The methanol and aqueous fractions of I. spicata significantly inhibited carrageenan induced edema (p < 0.001) with maximal percent inhibition of 45.9 and 39.6 respectively, observed at dose of 200 mg/kg. Similarly, these fractions significantly inhibited formalin induced edema (p < 0.001) with maximal effect (41.5 vs. 40.4%) observed at the same dose. The chloroform fraction did not show significant inhibition of paw edema at all dose levels in both models. Phytochemical analysis revealed differential distribution of secondary metabolites. These findings suggest that the plant indeed is endowed with anti- inflammatory activity, which could be probably attributed to active principles that are semi-polar to polar in nature. Keywords: I. spicata, anti-inflammatory activity, Indomethacin, Carrageenan, Formalin
Evaluation of Analgesic and Anti-Inflammatory Activities of Solvent Fractions of the Leaves of Moringa Stenopetala Bak.F. In Swiss Albino Mice
(Addis Ababa University, 2014-05) Tamrat, Yohannes; Nedi, Teshome (PhD); Shibeshi, Workineh(PhD)
Many people still experience pain and inflammation regardless of the available drugs for treatments. In addition, the available drugs have many side effects, which necessitated a quest for new drugs from several sources with medicinal plants being one of them. This study evaluated the analgesic and anti- inflammatory activity of the solvent fractions of Moringa stenopetala. Successive soxhlet and maceration were used as methods of extractions and Chloroform, methanol and water were used as solvents. Radiant tail flick latency, acetic acid induced writhing and carrageenan induced paw edema models were used to assess the analgesic and anti-inflammatory activities. The test groups received different doses of the three fractions 100 mg/kg, 200 mg/kg and 400 mg/kg. The positive control groups received either Morphine 20 mg/kg or Aspirin at 100 mg/kg or 150 mg/kg. The control groups received the vehicles distilled water or 2% Tween80, 10 ml/kg. In all models the chloroform fraction had protections only at a dose of 400 mg/kg. But, the methanol and aqueous fraction at all doses have shown a significant central and peripheral analgesic and anti-inflammatory activity having comparable effects with standards. Phytochemical screening test revealed differential distribution of secondary metabolites amongst the fractions and the metabolites identified either alone or in combination appeared to be responsible for the observed effect. This study showed the iv aqueous fraction being the most active fraction followed by the methanol and then chloroform fraction. Key words: Analgesic activity, anti-inflammatory activity, solvent fractions, Moringa stenopetala
Evaluation of Analgesic and Anti -inflammatory Activity of Moringa stenopetala Bak.(Moringaceae) in Mice
(Addis Ababa University, 2014-06) Geremew, Helen; Engidawork, Ephrem (PhD)
Moringa stenopetala Bak F.is commonly used in folk medicine as a single drug remedy to treat various aliments like; hypertension, headache, stomach disorders, asthma, diabetes and malaria. However, the use of the herb for treatment of pain and inflammation has not been scientifically investigated. Thus, in this experiment 80% methanol crude extract of the leaves of M.stenopetala was evaluated for its analgesic and anti-inflammatory properties using established animal models. Swiss albino mice of either sex were randomly divided into five groups of six mice per group. The negative control group was orally given 0.5 ml of distilled water. The positive control received standard drug (morphine 10 mg//kg, Acetyl salicylic acid 81mg/kg, Indomethacin 25mg/kg).The rest of the groups were treated with 80 % methanol extract of M. Stenopetala at doses of 200, 400 and 600 mg/kg.Animals were then subjected to a battery of tests including hot plate, tail flick, acetic acid induced writhing, and carrageenan induced paw oedema tests. M. stenopetala extract showed a dose-dependent significant reduction of pain in analgesia models (p<0.001) with 600 mg/kg dose producing the highest reduction. The extract significantly reduced carrageenan induced inflammation in a dose independent manner, in which the highest reduction of inflammation was observed at 400mg/kg. The data collectively indicate that 80% methanol extract of M. Stenopetala leaves have potential analgesic and anti-inflammatory activities against stimuli in the tested animals and can be recommended for further studies. Key words: M. stenopetala, analgesic activity, anti- inflammatory activity
Evaluation of the Antidepressant-like Activity of the Crude Extract and Solvent Fractions of Rosa abyssinica Lindley (Rosaceae) Using Rodent Models of Depression
(Addis Ababa University, 2014-06) Fekadu, Netsanet; Engidawork, Ephrem (PhD)
Depression is a disorder often manifested with symptoms at the psychological, behavioral and physiological levels. Herbal medicine holds a valuable place in the treatment of depression. It is also a reasonable alternative for developing novel drugs. Accordingly, 80% methanol extract of the fruits of Rosa abyssinica Lindley (Rosaceae) and its solvent fractions were assessed for their antidepressant-like effect using despair based models of depression including tail suspension test (TST) and forced swim test (FST). The effect of the crude extract on the locomotor activity was also assessed using the open field test (OFT). Animals were randomly assigned to five groups, (n=8). Negative control group received 2% Tween 80, whereas positive control group received imipramine (30 mg/kg). The test groups received 100 mg/kg, 200 mg/kg and 400 mg/kg of the crude extract or the solvent fractions of Rosa abyssinica. The crude extract at the doses of 200 mg/kg and 400 mg/kg significantly reduced the time of immobility (p<0.01) in the TST and FST. The aqueous fraction at 200 mg/kg displayed a significant reduction (38%, p<0.01) in time of immobility in TST which was superior to the effect of imipramine. The methanol fraction displayed a significant reduction in the duration of immobility (33.93%, p< 0.01) only at 200 mg/kg. Interestingly the ethyl acetate fraction was devoid of activity. No significant change in locomotor activity was detected in all the doses of the crude extract and imipramine in OFT. These results suggest that this plant holds a potential value for the management of depression. Keywords: Rosa abyssinica Lindley (Rosaceae), Depression, Antidepressant, crude extract, solvent fractions
Evaluation of the anti-diarrheal activity of the solvent fractions of Croton macrostachyus Hocsht. ex Del. (Euphorbiaceae) leaves in mice
(Addis Ababa University, 2014-10) Degu, Amsalu; Engidawork, Ephrem (PhD); Shibeshi, Workineh(PhD)
Traditional healers in Ethiopia use a wide range of medicinal plants with antidiarrheal properties. Among these, Croton macrostachyus is one such plant claimed to have an antidiarrheal activity in Ethiopian folklore medicine. Previous studies showed that the crude extract is endowed with the claimed property and this study was undertaken to further the claim by screening different fractions for the said activity so that it could serve as a basis for subsequent studies. The fractions were obtained by successive soxhlet extraction with solvents of differing polarity (chloroform & methanol) followed by cold maceration of the marc of the methanol fraction with distilled water. The antidiarrheal activity was evaluated using castor oil induced diarrheal model, charcoal meal test and anti-enteropooling test in mice. The test groups received various doses (300, 400, 500 mg/kg and an additional dose of 1000 mg/kg for the aqueous fraction) of the fractions, whereas positive controls received either Loperamide (3 mg/kg) or Atropine (5 mg/kg) and negative controls received vehicle (10 ml/kg). In the castor oil induced model, the chloroform (at all test doses) and methanol (at 400 & 500 mg/kg) fractions significantly prolonged diarrheal onset, decreased the frequency of stooling and weight of feces. The aqueous fraction was, however, devoid of significant effect at all doses tested. Similarly, in the enteropooling test, whilst the chloroform and methanol fractions produced a significant dose dependent decline in the weight and volume of intestinal contents, the aqueous fraction was without appreciable effect. Results from the charcoal meal test revealed that all the fractions produced a significant anti-motility effect either at all iv doses (chloroform fraction) or at middle and higher doses (methanol and aqueous fractions). Taken together, the present study demonstrated that the chloroform and methanol fractions possessed significant anti-diarrheal activity due to its inhibitory effect on castor oil induced gastrointestinal propulsion and fluid secretion. Nevertheless, the aqueous fraction showed only significant anti-motility effect at the higher dose (1000 mg/kg) employed in the study. Key words: Antidiarrheal activity, Castor oil induced diarrhea, gastrointestinal transit, anti-enteropooling, Croton macrostachyus
Evaluation of the Antidiarrheal Activity of 80% Methanol Extract of the Aerial Parts of Ajuga remota Benth in Mice
(Addis Ababa University, 2014-12) Yacob, Teshager; Nedi, Teshome (PhD); Shibeshi, Workineh(PhD)
In the Ethiopian traditional medicine, the aerial parts of Ajuga remota Benth ( Local name, Armagusa) is used in the treatment of diarrhea. Since this claim has not been investigated scientifically, this study was undertaken to evaluate the anti-diarrheal activity of 80% methanol extract of A. remota (MEAR) using experimental models in mice . The MEAR was administered at doses of (200, 400, 600 and 800 mg/kg ) to four groups of mice (six animals per group) orally in castor oil diarrhea model. Two other groups , one as control and the other as standard ( loperamide 5mg/kg ) were used for comparison with the treatment group. The effect of the extract on the other models, enteropooling and gastrointestinal transit models, was also evaluated using the same grouping and dosing . The extract at doses of 400, 600, and 800 mg/kg produced a dosedependent and significant inhibition both on the frequency and onset of diarrhea. The percentage purging frequency was 53.4%, 66.7%, 79.6% (p < 0.001; for all), and 66.7% (p < 0.001) at three doses of MEAR (400, 600, and 800mg/kg ) and with loperamide (5mg/kg ), respectively. The percentage inhibition in intestinal fluid accumulation was 42.5%, 62.1% , and 74.2% ( p < 0.001; for all ) at doses of 400, 600 and 800 mg/kg of MEAR, respectively. The MEAR also inhibited significantly (p<0.001) and in a dose dependent manner both the normal or castor oil induced intestinal transit. Phytochemical screening revealed the presence of secondary metabolites like alkaloids, flavonoids, terpenoids, tannins, phenolics, glycosides, steroids, and saponins which might have accounted for the antidiarrheal activity. To conclude, this study has shown that the hydroalcoholic extract of A. remota contains pharmacologically active substances with significant antidiarrheal activity in all the experimental models used in this study . Key words : Antidiarrheal, castor oil, enteropooling, gastrointestinal propulsion, Ajuga remota
Assessment of Antidiabetic Medication Adherence and Its Effect on Glycemic Control in Ambulatory Patients with Type 2 Diabetes at Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia
(Addis Ababa University, 2014-12) Tsehay, Tessema; Engidawork, Ephrem (PhD); Ahmed, Abdurezak (Assistant Professor)
Poor adherence to treatment of chronic diseases is a worldwide problem of striking magnitude. Adherence to long-term therapy for chronic illnesses in developed countries averages 50%. In developing countries, the rates are even lower given the paucity of health resources and inequities in access to health care. Poor adherence to recognized standards of diabetes care is the principal cause of development of complications of diabetes and their associated individual, societal and economic costs. Information on adherence to antidiabetic medications and glycemic control among Type 2 diabetes patients in Ethiopia is scanty. This study therefore sought to assess antidiabetic medication adherence and glycemic control among 322 ambulatory patients with Type 2 diabetes mellitus attending at the diabetic clinic of Tikur Anbessa Specialized Hospital (TASH). The study was a two phase, cross-sectional study conducted between 1 May-30 June 2014. Assessment of adherence was performed based on patients’ response to the validated four-item Morisky instrument and the most recent fasting blood sugar level was used for glycemic control. Adherence rate to antidiabetic medications was found to be 66.8%. Younger age, increased number of prescribed medications and job type (being a farmer/daily laborer) were significantly associated with antidiabetic medication noniv adherence. Most of the patients missed their medications because of forgetfulness. On the other hand, only 12.7% of patients attained adequate glycemic control. Male sex, younger age, low educational status, regular alcohol intake, exercise and dietary non-adherence were observed to be significantly associated with poor glycemic control. Antidiabetic medication adherence appeared to be positively associated with glycemic control (COR= 1.23, 95% CI: 0.6-2.5). Taken together, the findings indicated that adherence to antidiabetic drugs was suboptimal and glycemic control was poor, which warrants the need for health care providers engaged in diabetic care to aggressively address the issue. Key words: Antidiabetic Medications, Adherence, Type 2 Diabetes, Glycemic control, Fasting Blood Glucose
Factors Associated with Underutilization of Inhalation Corticosteroids among Asthmatic Patients Attending Tikur Anbessa Specialized Hospital
(Addis Ababa University, 2015-01) Ayele, Yohanes; Engidawork, Ephrem (PhD)
Inhalation Corticosteroids (ICS) is a cornerstone medicine for preventive therapy of persistence asthma. However, underutilization of ICS is common and little is known about factors contributing to this underutilization. The objective of this study was to assess factors associated with underutilization of ICS in asthmatic patients. A cross-sectional study involving interview was conducted among asthmatic patients attending chest clinic of Tikur Anbessa Specilized Hospital (TASH) from 1 May to 31 July, 2014. A total of 131 patients were included in the study. In addition, physicians working at the chest clinic of TASH were also requested to fill out a selfadministered questionnaire. A multivariate logistic regression was employed to examine the association between variables. Overall, underutilization of ICS from patients’ perspective was found to be 64.7%. Monthly income, comorbidity and manners of ICS use were found to be significantly associated with underutilization of ICS. Patients’ reported reasons for underutilization of ICS include; unaffordability, using only when symptoms appear, inaccessibility, side effects and recommendation by physicians. Similarly, physicians reported unaffordability, fear of side effects and dependency, and inaccessibility as reasons for underutilization of ICS. In this setting, prevalence of underutilization of ICS was high, and is associated with unaffordability and inaccessibility of ICS, patients’ poor knowledge of asthma and ICS, negative attitude toward ICS, and absence of local guideline for asthma management. Thus, concerned authorities need to take measures that ensure availability of ICS at an affordable price and increase awareness of patients on ICS and asthma. Key words: - Inhalation corticosteroids, Underutilization, Asthma
Assessment of Drug Related Problems in Medical Wards of Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia
(Addis Ababa University, 2015-01) Biset, Mohammed; Nedi, Teshome (PhD)
Drug related problems are common in hospitalized patients. Ten to thirty percent of hospital admissions are thought to be directly related to drug related problems. Drug related problems may lead to reduced quality of life, increase hospital stay, increase overall health care cost and even increase the risk of morbidity and mortality. Data regarding drug related problems in inpatient settings in Ethiopia is limited. This study was aimed to assess drug related problems in the internal medicine wards of Tikur Anbessa Specialized Hospital. A prospective cross sectional study was conducted on 225 patients admitted in medical wards of TASH. Drug related problems were identified through review of patients’ medical charts. In addition to this, discussion with patients and physicians was conducted to get supplementary information and clarification on some patient’s medical information. Data regarding patient characteristics, medications, diagnosis, length of hospitalization, investigation and laboratory results were collected. Epi Info 7 was used for data entry and data was analyzed using SPSS version 21. Descriptive statistics, cross-tabs, binary and multiple logistic regressions were utilized. P < 0.05 was used to declare association. Drug risk ratio was used to identify drugs that were prone to create DRP. DRP was found in 52 % of study subjects. Drug interaction (48 % of all DRPs) was the top ranking DRP followed by ADR (23%). Antibiotics were common to be involved in DRP followed by GI medicines, CNS drugs and medicines affecting the blood. Cimetidine, tramadol, heparin and warfarin were the top ranking drugs involved in DRP. Gentamycin, warfarin, nifedipin, cimetidine, simvastatin, prednisolone, digoxin and pethidine were drugs with the highest drug risk ratio. The number of drugs taken by the patient per day is an important risk factor for DRPs. There was no significant association between occurrence of DRP and sex, age, hospital stay and number of co-morbidity in the study subjects. Key words: Drug related problem, Tikur Anbessa Specialized Hospital, Medical wards

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