Investigation of gastroprotective efficacy of andrographolide at different doses on indometacine-induced gastric ulcer

Aim:Non-steroidal antiinflammatory drug(NSAID)-related gastric damage is a common dangerous side effect of this group of drugs. Proton pump inhibitors (PPI) have been used in the treatment of gastric ulcer for along time. More safer agents are needed to be developed. In our study, it was aimed to investigate gastroprotective effects of Andrographolide against the harmful effect of indomethazine(a member of NSAID group), which is important in gastric ulcer etiology. Method:Forty-eight male Wistar albino rats, each weighing 300-350 gr, 3-4 months aged, were used in the study. These fourty eight rats divided randomly to six group of eight. Groups were: control, indomethasine, lansoprazole, indomethazine + lansoprazole, indomethazine + andrographolide 15mg, indomethazine + andrographolide 30mg. While the control group was fed with standard feed and tap water, the other groups were starved for 24 hours before the experiment and 8 hours after drug administration, blood and tissue samples were taken. Macroscopic, histopathologic, and biochemical data are presented. In the macroscopic examination, the percentage of affected stomach surface area was calculated by using millimetric paper. In the histopathological examination, necrosis, bleeding, erosion and inflammatory infiltration were examined. Biochemically, the level of superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), glutathione peroxidase (GPx) were examined which play a role in the free radical metabolizm and malondialdehyde (MDA) level which is an indicator of lipid peroxidation is also examined. Results: The application of 15 mg and 30 mg of Andrographolide showed a statistically significant decrease in the macroscopic ulcer area and inflammatory response compared to the group given indomethacin alone. The mean ulcer area in the indomethacin group was 14,91 ± 5,44, whereas it was 8,56 ± 3,67 in the A+i15 group, and 6,06 ± 3,62 in the A+i30 group (P: 0.002). This result shows us, mean ulcer area is statistically significantly lower in the a+i15 group and the a+i30 group than in the indomethacin group. And also in the A+i30 group, the ulcer area was lower than in the a+i15 group. In terms of necrosis, hemorrhage and erosion scores, indomethacin group was higher on average score than a+i15 and a+i30 groups, but this difference was not statistically significant. When assessed in terms of GSH, the level of GSH in the control group was found to be statistically significantly higher than the indo, lan and indo+lan groups (p: 0.027). Although the decrease in GSH levels was limited in the andrographolide groups, the positive effect was not statistically significant. We could not demonstrate the positive effect of andrographolide between groups in terms of CAT, SOD, GPX and MDA. Conclusion: The positive effect of andrographolide on the prevention of macroscopic ulcer formation and histopathologically significant reduction in inflammatory response suggest that it could be used as a gastroprotective agent in the future. Key Words: Andrographolide, gastric ulcer, indomethacin