Avaliação do potencial anti-nociceptivo e antiinflamatório do ácido pipérico

Abstract

Drugs currently used in pain and inflammation are responsible for a large number of adverse effects, due to chronic use, producing in the patients a decrease of symptoms, but not an overall improvement in quality of life, therefore it is of extreme importance to search for new drugs. Piperine is the main active compound of black pepper (Piper nigrum), known in Brazil as black pepper, popularly used by several beneficial effects. Studies in vitro and in vivo show that piperine has functional involvement in antidepressant, hepatoprotective, anti-metastatic antiparasitic, antithyroid, immunomodulatory, anti-inflammatory and analgesic effects. To improve the selectivity and potency, molecular changes were made in the piperine, obtaining the piperic acid. The objective of this study was to evaluate, through of models of acute and chronic pain, and inflammation; a potential nociceptive and anti-inflammatory compound. In the model of writhing induced by acetic acid was observed a percentage inhibition of writhes of 77,9% compared to the control, in the highest dose tested (10mg / kg). In the formalin test, the compound inhibited both phases of the test, wich the dose of 10mg/kg The inhibitory effect was 30% in stage 1 and stage 2 at 67%. The increase in the latency time in tail flick test had an earlier action compared to morphine and the piperic acid increased the latency time in 58% in 80min time in relation to baseline. We investigated the possible pathways involved in the mechanism of action of the compound by prior administration of antagonists in the tail flick test. We found that the muscarinic antagonist, atropine, was able to completely inhibit the effect of the compound, demonstrating the involvement of the cholinergic pathway in the mechanism of action. The opioid and nitrergic pathways and the potassium channel ATPdependent are not involved in the mechanism of action, since these antagonists do not inhibit the effect of the compound. The compound was able to inhibit capsaicin-induced nociception, capsaicina is agonist TRPV1, in 45,34% demonstrating the involvement of TRPV1. The von Frey test evaluate allodynia after chronic constriction of the sciatic nerve. In this test, the compound did not show antinociceptive activity with the doses tested. The open field test was used to determine the influence of the compound on the animal's mobility, and we observe that the action of the compound did not interfere on animal's motor performance. The antiinflammatory activity was evaluated in models of inflammation induced by carrageenan. In the paw oedema test, the compound significantly reduced the oedema at doses of 5 and 10 mg/kg. In the air pouch test, we found that the leukocyte migration was reduced, as well as the production of TNF-α and IL-1β. The piperic acid was shown to be selective for COX-1 in the assessment of enzymatic activity of COX-1 and COX-2. We suggest that the effects of piperine can be mediated primarily through the portion of the molecule related to piperic acid