The objective of this dissertation is to study the safety of extracts of Sweet flag (Acorus calamus l.) leaves, to identify their pharmacological properties and to establish potential in the treatment of inflammatory diseases of gastrointestinal tract.
By studying the acute toxicity of the extracts Sweet Flag leaves, they are classified as class IV – Relatively non-toxic substances (according to the classification of K.K. Sidorov). During the study it was found that extracts of Sweet Flag leaves have anti-inflammatory, capillary strengthening, gastro-protective, hepatoprotective properties and a moderate antidepressant effect. Among all studied extracts dealcoholized extract of Sweet Flag leaves is selected as the most potent extract with gastro-protective and hepatoprotective properties – the extract is provisionally named «DELL».
In the model of carrageenan and histamine edema extracts of Sweet Flag leaves revealed anti-exudative properties. Alcohol-water extract of Sweet Flag leaves has the greatest anti-exudative activity (further referred as RSVELA). The capillary-strengthening activities of Sweet Flag leaves extracts on the models of vascular and tissue permeability are established as well. According to the degree of capillary-strengthening effect, DELL is the most effective (p≤0.05) comparing to the control group and groups treated with quercetin and sodium diclofenac. A conditionally therapeutic dose of DELL, equal to 1 ml/kg, is established.
In the models of aspirin, reserpine and ethanol-prednisolone induced gastric ulcers extracts of Sweet Flag leaves shows antiulcer activities. The antiulcer activity of DELL in the aspirin model (69.4%) is superior to RSVELA, and the activities of RSVELA correspond to the action of the comparison drug – quercetin (22.2%). In the reserpine model of gastric ulcers in mice, the efficiency of DELL (68.5%) exceeds the activity of the comparison drug quercetin (34.2%). In the model of ethanol-prednisolone gastric ulcer DELL exceeds the comparison drug – ranitidine on a number of indicators, such as: reduction of the intensity of lipoperoxidation processes; improvement of the functioning of the antioxidant system; reduction of bloating, reduction of intestinal edema and reduction of hyperemia of the gastric mucosa. The gastroprotective effect of DELL is confirmed by histological studies.
In the models of paracetamol and carbon tetrachloride-ethanol hepatitis DELL shows hepatoprotective activities according to the criteria of normalization of prooxidant-antioxidant balance in the liver (decreasing the levels of 8-isoprostane by 1.8 times, increasing the levels of reduced glutathione by 1.5%, decreasing the levels of AST, ALT and γ-GTTP, decreasing manifestations of cholestasis (decreasing the level of alkaline phosphatase, (p≤0.05). Hepatoprotective effect of DELL is confirmed by histological studies.
DELL has a stimulating effect on locomotor, orientation and explorative activities. It improves physical activities and endurance as well. Also, DELL has a moderate analeptic effect on the emotional state of the animals, which may be due to barbiturates antagonism. In the model of reserpine-induced depression, DELL shows a thymoleptic effect, which is manifested by an increase in the latent time of immobility and a decrease in the duration of immobility, a decrease of hypothermia and blepharoptosis.
The main pharmacological properties of DELL are identified as antioxidant and membrane stabilizing activities.
The results of this preclinical research may contribute to the development of drugs on the basis of Sweet Flag leaves extracts for the treatment of inflammatory diseases of gastric and intestinal tract (gastritis, hepatitis, etc.) and for the treatment of neurological disorders induced by oxidative stress
