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Item In-vivo and In-vitro Mechanistic Study in The Antidiarrheal Activity of Hydro-alcoholic Extract of Ocimum lamiifolium HOCHST. EX BENTH Leaves.(Addis Ababa University, 2023) Beyene,Dinberu; Shibeshi,Workineh(PhD); Umer,Shemsu(PhD)Ocimum lamiifolium is used in the management of various diseases such as fever, malaria, headache, cough, and gastrointestinal disease (diarrhea). This study was undertaken to evaluate the in-vivo and in-vitro mechanistic studies in the antidiarrheal activity of hydro-alcoholic extracts of the leaves of O. lamiifolium. The anti-diarrheal activity was assessed using a castor- oil-induced diarrhea model, charcoal meal test, and entero-pooling test in mice. The standard drug loperamide 3 mg/kg was given to the positive control. Different doses of the hydro- alcoholic extract of O. lamiifolium (100, 200, and 400 mg/kg were given to the test groups, and distilled water (10 ml/kg) was given to negative controls. The ex-vivo spasmolytic activity was evaluated using organ bath perfusion in isolated guinea pig ileum. The mechanistic study was also explored using a castor-oil-induced diarrheal model in the presence of naloxone (opioid antagonist). In the mechanistic study, the test group received 400 mg/kg extract with naloxone 2 mg/kg, the positive control received loperamide 3 mg/kg with naloxone 2 mg/kg, and the negative control received distilled water 10 ml/kg with naloxone 2mg/kg. In the castor oil-induced diarrhea model, all the tested ingredients significantly prolonged the onset of diarrhea and reduced the number of defecation (p<0.05). However, the mean weight of wet and total feces was significantly reduced by only the higher doses (200 and 400 mg/kg) (p<0.05). All doses also produced a significant (p<0.01) reduction in mean weight and mean volume of intestinal contents in the entero-pooling study. Similarly, in the charcoal meal test, all the study doses of the substance also produced significant (p<0.001) antimotility effects. In the mechanistic studies, the percentage inhibition of diarrhea by 400 mg/kg of the extract in the presence of naloxone (2 mg/kg) is 64.69%. In this case, charcoal meal traverse is significantly reduced by the extract compared to the control p<0.001. However, in the presence of naloxone (2mg/kg), the percentage inhibition by loperamide 3mg/kg is 6.89%. In the ex-vivo studies, the percentage of response or relaxation produced by the extract was 20%, 65%, and 75% at the doses of 0.1, 0.2, and 0.4 ml respectively. The doses that produced 50% maximal relaxation (EC50) by the extract were 0.18 ml or 1.8 mg of hydro-alcoholic extracts of O. lamiifolium. In conclusion, this study revealed that the hydro-alcoholic leaf extract of O. lamiifolium exhibits considerable anti- diarrheal activity because of its inhibitory effect on gastrointestinal motility and secretion. This is partly mediated through blockage of muscarinic acetylcholine receptors but not opioid receptors.