DSpace Collection: Thesis - Pharmacology

IN VIVO ANTIMALARIAL ACTIVITY OF THE ROOT EXTRACTS AND FRACTIONS OF CLERODENDRUM MYRICOIDES IN PLASMODIUM BERGHEI INFECTED MICE

Wed, 16 May 2012 12:37:21 GMT

Title: IN VIVO ANTIMALARIAL ACTIVITY OF THE ROOT EXTRACTS AND FRACTIONS OF CLERODENDRUM MYRICOIDES IN PLASMODIUM BERGHEI INFECTED MICE

Authors: TIGIST, BELAY

Abstract: Malaria is one of the six infectious diseases that account for half of all premature deaths; and for over 40% of the world's population from more than 90 countries living with the risk of the disease. Plants are essential sources for the battle against it. C. myricoides is found in different parts of Ethiopia and its vernacular name is ‘misiritch’ in Amharic. It is traditionally used in Ethiopia for different purposes such as treatment of gonorrhea, colic, gout, swelling, measles, gland TB, eye diseases, malaria, rabies, as wound dressing and as aphrodisiac.The present study therefore attempted to evaluate the antimalarial activity of the root extracts of C. myricoides in mice infected with P. berghei and to determine LD50 and phytochemical screening. In this study, phytochemical screening has been done using standard methods. 4-days peter’s test was used to determine parasite inhibition, PCV was determinied by Wintrob’s method, effects against loss of body weight, effect on reduction in temperature and improvement on survival time were determined. LD50s of the crude extracts have been also done. The crude aqueous, crude hydroalcoholic, dichloromethane fraction of crude aqueous, butanol fraction of crude hydroalcoholic extracts of the roots of C.myricoides significantly (P<0.05) inhibited parasitemia of malaria. These parasitemia suppression observed was comparable to that observed with Solanum indicum leaves.The activity is due to components in the plant which might have retarded the multiplication of the parasites in the blood. The crude aqueous, crude hydroalcoholic, dichloromethane fraction of aqueous, butanol fraction both crude aqueous and hydroalcoholic extracts of the roots of C.myricoides prevented weight loss (P≥05)especially at high doses. This also occurs for plants like Withania somnifera. No weight gain was observed which may be due to the presence of compounds with appetite suppressing effect. The crude aqueous,crude hydroalcoholic, dichloromethane fraction of aqueous, butanol fraction of crude hydroalcoholic and chloroform fraction of crude hydroalcoholic extracts (P≥05) of roots of C.myricoides prevented reduction in PCV. The parasites caused destruction of red blood cells leading to reduction in PCV. The prevention in reduction of PCV may be due to the compounds in the extracts. The crude aqueous and crude hydroalcoholic extracts improved((P≥05)survival time. xi From this study, it can be observed that the crude aqueous extract, crude hydroalcoholic extract, dichloromethane fraction of crude aqueous extract and butanol fraction of crude hydroalcoholic extract has reduced parasitemia, prevents loss of body weight, protects against PCV reduction and improved mean survival time. Chloroquine (10mg/kg) has shown 100% parasitemia inhibition and all other parameters measured in mice returned to normal. In this study, the crude extracts showed better antimalarial activity than the fractions since different compounds may be found which have synergistic effect and some secondary metabolites protect other metabolites (as antioxidants) and break of this association can accelerate degradation. In this study, alkaloids and saponins have been detected which might be responsible for the antimalarial activity. The hydroalcoholic crude extract likely to contain flavonoids, whitanides and phytosterols while polypenols , saponins ,tannins and alkaloids are likely to be present in the crude aqueous extract. Thus the synergistic activity observed in the crude extracts and the activity in the fractions may be due to these compounds. The oral LD50 of the crude aqueous and hydroalcoholic extracts were 1134.42mg/kg and 1629.99mg/kg, respectively. From the present study, it can be concluded that crude aqueous extract, crude hydroalcoholic extracts, of roots of C.myricoides have antimalarial activity at much lower doses than the LD50s hinting the safe and efficacious nature of the plant. The dichloromethane fraction of crude aqueous extract and butanol fraction of crude hydroalcoholic extract also have antimalarial effect. Further fractionation was also not possible due to low yield.Thus, the active ingredients should be isolated by different extraction methods.

GASTROINTESTINAL EFFECTS OF CRUDE KHAT (CATHA EDULIS F) EXTRACT FOLLOWING ACUTE AND SUB-CHRONIC ADMINISTRATION IN RODENTS

Fri, 11 May 2012 14:25:17 GMT

Title: GASTROINTESTINAL EFFECTS OF CRUDE KHAT (CATHA EDULIS F) EXTRACT FOLLOWING ACUTE AND SUB-CHRONIC ADMINISTRATION IN RODENTS

Authors: WINTANA, TADESSE

Abstract: Khat (Catha edulis F) belongs to the Celastraceae family and is a dicotyledonous evergreen shrub/tree used for recreation and alleviation of fatigue in several countries of East Africa and South Arabia. Recently, this habit has spread considerably, raising concern in view of medical and socio-economic consequences of khat consumption. Even though khat has several medicinal, social, and economical values, there are numerous reports regarding its gastrointestinal tract (GIT) adverse effects. As the effects of khat chewing on digestive system mentioned in earlier studies were based on clinical observations, the present study was designed to evaluate the GIT activity of the crude khat extract after acute and sub-chronic administration using different rodent models and parameters used for ulcer and motility measurement were quantified. For acute study, animals were randomly assigned into different groups. Negative control received Tween 80 2% in distilled water, whereas positive controls were given ranitidine (pylorus ligation and cysteamine HCl models), misoprostol (indomethacin induced gastric ulcer), and loperamide (castor oil induced diarrhea and enteropooling assay). The other group received different doses of crude khat extract: 100 mg/kg, 200 mg/kg and 300 mg/kg. For sub-chronic study, one group was administered vehicle and served as control, whilst the other three were administered three doses of khat extract (100, 200, and 300 mg/kg) for 45 days. Acute khat administration in pylorus ligation model was shown to aggravate ulcer compared to controls in the highest dose used, as evidenced by increased volume of gastric acid secretion (p<0.05), total acidity (p<0.05) and ulcer index (p<0.01). Similar results were obtained in indomethacin induced gastric ulcer model where 300 mg/kg khat extract increased mucosal damage as demonstrated by a significant reduction in mucin content compared with misoprostol (p<0.001) and vehicle (p<0.05) treated animals. Khat at 300 mg/kg was also shown to accentuate duodenal ulcer induced by cysteamine HCl by significantly increasing (p<0.01) ulcer area as compared to vehicle-treated rats. Whilst ranitidine was shown to offer antiulcer activity in the models tested, khat at 100 mg/kg was devoid of any significant ameliorating or accentuating effect. Surprisingly, subviii chronic administration of khat at all doses failed to produce neither gastric nor duodenal ulcer. In castor oil induced diarrhea, 300 mg/kg (p<0.001) and 100 mg/kg (p<0.01) khat extracts significantly decreased the number of watery fecal discharge against vehicle treated rats. In addition, 300 mg/kg dose decreased (p<0.05) weight and volume of intestinal content in castor oil induced enteropooling model. In sub-chronic studies, 300 mg/kg and 200 mg/kg khat extracts significantly inhibited intestinal motility in in-vivo gastrointestinal motility model by 53.2% and 48.6%, respectively. On the other hand, weight change on sub-chronic khat extract administration was observed and the change became significant at the 3rd (p<0.05), 4th and 5th week (p<0.01), and 6th week (p<0.001) with 300 mg/kg dose. While in 200 mg/kg decline of weight at 4th week (p<0.05) and for following weeks (p<0.01) was obtained. In conclusion, acute use of khat at higher dose in the presence of ulcerogenic agents could aggravate gastric and duodenal ulcer, while sub-chronic khat administration alone did not produce ulcer. Furthermore, acute and sub-chronic administration of khat extract at higher dose produced a significant constipating activity. And sub-chronic administration of khat extract at higher dose markedly decreased body weight. These effects collectively indicate that khat consumption in large amount and for a longer period of time is associated with adverse GIT outcomes.

IN-VIVO ANTI-INFLAMMATORY ACTIVITY OF THE LEAF EXTRACTS AND FRACTIONS OF OCIMUM SUAVE IN MICE MODEL

Thu, 03 May 2012 12:21:20 GMT

Title: IN-VIVO ANTI-INFLAMMATORY ACTIVITY OF THE LEAF EXTRACTS AND FRACTIONS OF OCIMUM SUAVE IN MICE MODEL

Authors: BIRHANETENSAY, MASRESHA

Abstract: 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 its 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.

INVESTIGATION OF ANTIHYPERGLYCEMIC AND HYPOGLYCEMIC ACTIVITY OF AJUGA REMOTA AND SYZYGIUM GUINEENSE ON MICE

Thu, 03 May 2012 07:08:52 GMT

Title: INVESTIGATION OF ANTIHYPERGLYCEMIC AND HYPOGLYCEMIC ACTIVITY OF AJUGA REMOTA AND SYZYGIUM GUINEENSE ON MICE

Authors: TEMESGEN, WORKU

Abstract: ABSTRACT The leaves of Ajuga remota and Syzygium guineense are traditionally used in Ethiopia for management of diabetes mellitus. The aim of this study was to evaluate antidiabetic effect of the aqueous and hydro alcoholic crude extracts of A.Remota and S.guineense on alloxan induced diabetic and normoglycemic mice and to carry out acute toxicity test of the extract with better activity. The results showed that hydro alcoholic extract of A.remota reduced significantly (p<0.05) the blood glucose level of alloxan induced diabetic mice at doses of 250 and 500mg/kg, one to two hours after treatment. After three hours of treatment the blood glucose level, however started to rise. At a dose of 1000mg/kg the extract did not significantly reduce the blood glucose level. The used three dose levels 250,500 and 1000mg/kg produced no effect on normoglycemic mice. The aqueous extract of A.remota did not reduce the blood sugar level of both diabetic and normoglycemic mice. Results of the present study on the hydro alcoholic extract of S.guineense did not show any significant reduction in blood glucose level of both normoglycemic and alloxan induced hyperglycemic mice. However, the aqueous extract reduced the blood glucose level of both normoglycemic and diabetic mice at all doses tested i.e. 50,100 and 200mg/kg in time dependent manner starting from half an hour after treatment. The aqueous extract of S.guineense was found to be more active; it was fractionated by using buthanol and dichloromethane and tested for antidiabetic action. The buthanol fraction and the aqueous residue were found active in both diabetic and normoglycemic mice. Dichloromethane fraction did not, however show significant reduction in both normoglycemic and diabetic mice. Phytochemical screening of the aqueous crude extract of S.gineense revealed the presence of secondary metabolites including Chromophores, polyphenols, Saponins, phytosteroids, flavonoids and alkaloids which might be accounted to the antidiabetic activity. Acute toxicity study showed that the non toxic nature of the aqueous extract of S. gineense up to 30 times its maximum effective dose and its LD50 was found >6000mg/kg.