Pharmacological potential of alkylamides from Acmella oleracea flowers and synthetic isobutylalkyl amide to treat inflammatory pain.

Abstract

Acmella oleracea ("jambu") is an Amazonian plant rich in alkylamides. Its flowers are widely used in folk medicine to treat toothache due to tingling, numbness, and local anaesthesia caused in the mouth. Our group previously demonstrated that the intraplantar (i.pl.) injection of an alkylamide-rich hexane fraction (HF) obtained from jambu flowers and a synthetic isobutylalkyl amide (IBA) displayed antinociceptive and anesthetic effects in acute pain models. Thus, here we evaluated the effects of HF and IBA on carrageenan-induced acute inflammation. Mice were pretreated with HF or IBA (0.01, 0.1, and 1µg/20µL, i.pl.) 15min before carrageenan injection (300µg/20µL, i.pl.). Mechanical allodynia and paw oedema were evaluated previously (basal) and at 0.5 until 6h following carrageenan. Both HF and IBA at 0.1µg promoted effective and long-lasting antiallodynic and anti-oedematogenic activities until 3 and 5h, respectively, in comparison to the different doses evaluated. At the inflammatory peak, the plantar surfaces were excised for measurement of inflammatory and oxidative stress parameters. HF and IBA (0.1µg) reduced the myeloperoxidase activity, TNF-α and IL-1β levels, prevented the production of lipid hydroperoxides, and the decrease of antioxidant agents, namely superoxide dismutase and catalase activities, and glutathione contents. Furthermore, only HF maintained IL-10 levels and decreased PGE2 synthesis. On the basis of the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, HF and IBA are devoid of antioxidant activity in vitro. Collectively, our results demonstrated the promising anti-inflammatory effect of local pretreatment with alkylamides, supporting the potential of these molecules to treat acute inflammatory pain conditions.