Prospecção biotecnológica de um novo diterpeno isolado de folhas de Croton argyrophylloides sobre ratos hemiparkinsonianos

Abstract

Parkinson's disease is a chronic degenerative disease of unknown etiology, caused by progressive loss of dopaminergic neurons, neurochemical and neurobehavioral abnormalities that are reflected in motor control dysregulation, causing severe long-term disability. Croton argyrophylloides is a small northeastern Brazilian shrub widely used by traditional folk medicine for the treatment of various diseases. Several studies indicate that oxidative stress and pro-inflammatory events are related to the apoptotic process that affects the loss of dopaminergic neurons in PD. In this context, the present study analyzed the antioxidant and neuroprotective effect of a new diterpene (MP-1) isolated from the leaves of C. argyrophylloides, on the DPPH inhibition test and in rats submitted to the 6-OHDA-induced Parkinson's disease model, respectively. For the evaluation of the reducing activity, the DPPH radical capture test was performed, in which 6 different concentrations (10-2000 μg / mL) of MP-1 dissolved in DMSO1% were tested. Ascorbic acid was used as a positive control. Male Wistar rats (250-300g) were used to evaluate the MP-1 neuroprotective potential, which were submitted to the PD disease model by intra-atrial injection of 6-OHDA (21 μg / animal) and after 10 minutes, treated with said bioactive (MP-1) by intracranial route only once. On the 14th day of treatment the animals were submitted to specific behavioral tests (Open Field, Rotarod and Rotational Test induced by apomorphine) and, after euthanasia and dissection of the cerebral areas (ipsi and contralateral striatum, Hippocampus and Pre Frontal Cortex), (determination of nitrite / nitrate levels, MDA and GSH) were performed. The results showed that diterpene MP-1 showed a reducing effect, being able to neutralize more than 50% of the DPPH radicals, presenting very high antiradicalar efficiency and a short reaction time. In addition, a neuroprotective effect can be observed in vivo in motor damage recovery, with increased spontaneous exploratory activity and gain of body mass by the animals. The compound was also able to prevent neurotoxin-induced neurochemical changes by reducing levels of nitrite / nitrate and MDA. However MP-1 was not able to induce the cytoprotective response via GSH. These findings demonstrate an antioxidant and neuroprotective effect of MP-1, which possibly acts on the capture of free radicals, attenuating neurotoxic injuries caused by reactive molecules, with important implications for future studies and their application for the development of new therapeutic strategies for PD.