Mecanismo de ação da atividade antinociceptiva e anti-inflamatória do (-) - mirtenol

Abstract

The essential oils of herbs have a variety of bioactive compounds, such as monoterpenes. These monoterpenes have several pharmacological activities described as analgesic, anti-inflammatory, antidepressant and anticonvulsant, among others. The (-)- myrtenol is a monoterpene alcohol monocyclic, of pleasant odor, used in the cosmetics industry. However, the absence of research on possible pharmacological activities of this monoterpene has encouraged the present research. This study investigates the effect of (-)- myrtenol, intraperitoneally in adult male Swiss mice under experimental models of pain and inflammation. Initially, the research was initiated with lethal dose 50 (LD50) of monoterpene, in order to establish safe doses for subsequent tests. To investigate the action profile of monoterpene in the central nervous system, a pharmacological screening behavior was carried out, the effect of which in animals treated with (-)- myrtenol was that of analgesia. Then methodologies were conducted to evaluate the antinociceptive activity. The (-)- myrtenol (25, 50 and 100 mg/kg, i.p) increased the latency to the onset of abdominal writhing induced by acetic acid and reduced the number of writhing when compared to the control group. In the formalin test, using the same doses, (-) myrtenol did not alter the duration of paw licking in the neurogenic phase (0-5 min), but it inhibited significantly (p <0,001) the time of paw licking along the inflammatory phase (15-30 min). In the test of nociception induced by glutamate, the three doses of monoterpene reduced time of paw licking. In the hot plate test, which is sensitive and specific to drugs that act through a central mechanism, the (-)- myrtenol did not alter the paw withdrawal latency. With these results, we propose that the antinociceptive action of (-)- myrtenol may be a peripheral and not central mechanism of action. In an attempt to elucidate the mechanism of action involved in the antinociceptive effect of (-)- myrtenol, pharmacological tools were used in the formalin test. The antinociception produced by (-)- myrtenol (100 mg/kg, i.p) was reversed by naloxone (5 mg/kg, s.c) naloxonazine (10 mg/kg, s.c), glibenclamide (10 mg/kg, s.c), L-NOARG (50mg/kg, i.p) and yohimbine (0,15 mg/kg, i.p) only in the second phase of the formalin test. In view of the outstanding action of monoterpene in the second phase of the formalin test, we have investigated its possible anti-inflammatory activity. In this evaluation, treatment with (-)- myrtenol (50 and 100 mg/kg, i.p) was effective in reducing the paw edema induced by carrageenan (500 mg / paw), prostaglandin E2 (5 nmol / paw) and bradykinin (3 nmol / paw) at all times tested. In the model of carrageenan-induced peritonitis (1%), the monoterpene decreased the influx of leukocytes and also the levels of IL-1&#946; and TNF-&#945; in peritoneal fluid. Therefore, this study has demonstrated that (-)- myrtenol has antinociceptive activity with the participation of opioid receptor &#956;1, K+ATP channels, oxidonitrergic and adrenergic &#945;2. Furthermore, (-)- myrtenol has exhibited anti-inflammatory activity by inhibiting the formation of paw edema and reduced leukocyte influx, possibly by inhibiting the production of pro-inflammatory cytokines IL-1&#946; and TNF-&#945;.