Investigation of antidepressant effect of gentiana olivieri in rats

Aim: Many synthetic antidepressant drugs used in depression treatment show low response rates and even produce adverse side-effects such as hepato/cardiotoxicity, appetite, sexual dysfunction, and sleep disorder, in depressed patients. Therefore, it is desirable to seek antidepressants in medicinal plants; such materials are expected to show fewer side-effects. In this context, we investigated the antidepressant effect of Gentiana olivieri Griseb. (Gentianaceae). Flowering herbs of G. olivieri known with a local name in Turkish as "Afat", is traditionally been used in south-east Anatolia as bitter tonic, stomachic and to combat some mental disorders including depression in the different regions of Turkey. The aim of this study is to investigate the antidepressant effects of G. olivieri ethanol extract in different doses and the possibility of synergistic interactions with imipramine in combinations of different doses and to evaluate the toxicity. Material and Method: The herbal extracts administered orally (1000, 500 and 200 mg/kg/day) alone and in combination of imipramine (10 mg /kg) for 7 days in the forced swim test, and for 3 weeks during the chronic stress model; imipramine at 10 mg/kg/day given orally as a positive control. Animals decapitated at the end of the study and TBARS, SOD, GSH levels in brain and liver tissues; serotonin, noradrenaline, dopamine and MAO-A levels in brain tissue were examined. Also changes in total body weight and serum corticosterone levels were evaluated. Results: The results showed that oral administration of the imipramine, G. olivieri ethanol extract in different doses alone or in combination of imipramine significantly reduced the duration of immobility in forced swim test; produced beneficial effects on the stressed rats by effectively improving chronic stress induced low sucrose consumption and reducing serum corticosterone levels. Increased brain serotonin, noradrenaline and reduced MAO-A levels, improvement in antioxidant parametres were also observed in brain tissue. Imipranine did not improved the antioxidant parametres induced by chronic stress in liver tissue, however improvment in axtioxidant parametres are shown when the herbal extract administrated alone or in combination of imipramine. There was no significant difference in body weight and locomotor activity among the treatment groups. Conclusion: These results suggest that the antidepressant property of G. olivieri might be attributed to its attenuating abnormalities in monoaminergic system functions in brain, improvement antioxidant levels, and HPA axis, although underlying mechanism still remains to be further elucidated. The combination use of G. olivieri with antidepressant drugs such as imipramine may reduce the side effects related to liver.