Riparina-I na reversão dos efeitos centrais induzidos por corticosterona em camundongos: possível envolvimento do estresse oxidativo e da via nitrérgica.

Abstract

Current pharmacological therapy has presented limitations that drive the search for new drugs. Substances with antioxidant and neuroprotective action are potential antidepressant agents. In this context, natural products emerge as a potential source of new drugs. Previous studies with riparin-I, an isolated alcamide of the Aniba riparia plant, presented promising results. It has been found that riparin-I has anti-inflammatory and antidepressant and anxiolytic effects in rodents. The last two effects were verified in an acute stress model applied for primary screening of substances with central effect. Considering previous studies that demonstrated the safety of rip-I in toxicity tests and the antioxidant potential of alcamides, the main objective of the present study is to evaluate the anti-depressant effect of rip-I, in an animal model of treatment-resistant depression, as well as investigating the possible involvement of antioxidant and nitrergic pathways in the generation of this effect. For this, mice were exposed to the corticosterone-induced depression model and applied the reversal protocol. The efficacy of the treatment was verified by predictive behavioral tests of antidepressive, anxiolytic, antipsychotic and cognitive-type effects, as well as, neurochemical tests - dosage of parameters of oxidative stress and Brain Derived Neurotrophic Factor (BDNF). The rip-I effects profile led us to evaluate the interaction of the substance with the sigma-1 pluripotent receptor. The administration of rip-I reversed the effects of corticosterone on the time of immobility in the forced swim and tail suspension tests, which is predictive of antidepressant effect, and on the number of rearing and percentage of pre-pulse inhibition, the which is predictive of antipsychotic activity, besides regulating parameters of oxidative stress in brain areas related to depression. The molecular modeling study also revealed the potential interaction between rip-I and the sigma-1 receptor, but further study with receptor pharmacological antagonist will be useful to evaluate the influence of this interaction on rip-I triggered central effects. This study provides unprecedented experimental data and opens perspectives for further studies that may culminate in a future therapeutic use of rip-I in the treatment of conditions associated with elevated glucocorticoid levels, such as Major Psychotic Depression.