Two New ßN-Alkanoyl-5-Hydroxytryptamides with Relevant Antinociceptive Activity.

In this work, we describe a new route for the synthesis and the antinociceptive effects of two new ßN-alkanoyl-5-hydroxytryptamides (named C20:0-5HT and C22:0-5HT). The antinociceptive activities were evaluated using well-known models of thermal-induced (reaction to a heated plate, the hot plate model) or chemical-induced (licking response to paw injection of formalin, capsaicin, or glutamate) nociception. The mechanism of action for C20:0-5HT and C22:0-5HT was evaluated using naloxone (opioid receptor antagonist, 1 mg/kg), atropine (muscarinic receptor antagonist, 1 mg/kg), AM251 (cannabinoid CB1 receptor antagonist, 1 mg/kg), or ondansetron (5-HT3 serotoninergic receptor antagonist, 0.5 mg/kg) 30 min prior to C20:0-5HT or C22:0-5HT. The substances both presented significant effects by reducing licking behavior induced by formalin, capsaicin, and glutamate and increasing the latency time in the hot plate model. Opioidergic, muscarinic, cannabinoid, and serotoninergic pathways seem to be involved in the antinociceptive activity since their antagonists reversed the observed effect. Opioid receptors are partially involved due to tolerant mice demonstrating less antinociception when treated with both compounds. Our data showed a quicker and simpler route for the synthesis of the new ßN-alkanoyl-5-hydroxytryptamides. Both compounds demonstrated significant antinociceptive effects. These new compounds could be used as a scaffold for the synthesis of analogues with promising antinociceptive effects.

Wound healing properties of Copaifera paupera in diabetic mice.

Copaifera oleoresin is one of the most used natural products in popular medicine all over the world. Among other effects (i.e., anti-inflammatory, antinociceptive, microbicidal) one of the most well-known is its wound healing capacity. However, the mechanism by which the oleoresin presents its effect is still not clear. In this study, our aim was to evaluate the wound healing capacity of oleoresin obtained from Copaifera paupera, its mechanism of action and identify its major components. For these purposes, diabetic Swiss Webster mice were topically treated with oleoresin (100, 150 or 200 mg/kg) for 14 consecutive days after an excision was performed in the back of the mice. Cytokines, wound retraction and histological evaluation were conducted at 3, 7 and 10 days (for cytokines); 0, 3, 7, 10 and 14 days (for wound retraction); and 7 and 14 days (for histological evaluation). Our data indicate that oleoresin significantly reduced production of MCP-1 and TNF-α at days 7 and 10 post-excision and increased IL-10 production at both days. All treatments demonstrated an effect similar or higher to that in collagenase-treated mice. Histological evaluations demonstrated that higher dose treatment resulted in better resolution and closure of the wound and higher levels of collagen deposition and indexes of re-epithelialization even when compared with the collagenase-treated group. The treatment with oleoresin from Copaifera paupera demonstrated that it is even better than an ointment routinely used for improvement of wound healing, suggesting this oleoresin as an option for use in diabetic patients.

Anti-Inflammatory Properties and Chemical Characterization of the Essential Oils of Four Citrus Species.

Citrus fruits have potential health-promoting properties and their essential oils have long been used in several applications. Due to biological effects described to some citrus species in this study our objectives were to analyze and compare the phytochemical composition and evaluate the anti-inflammatory effect of essential oils (EO) obtained from four different Citrus species. Mice were treated with EO obtained from C. limon, C. latifolia, C. aurantifolia or C. limonia (10 to 100 mg/kg, p.o.) and their anti-inflammatory effects were evaluated in chemical induced inflammation (formalin-induced licking response) and carrageenan-induced inflammation in the subcutaneous air pouch model. A possible antinociceptive effect was evaluated in the hot plate model. Phytochemical analyses indicated the presence of geranial, limonene, γ-terpinene and others. EOs from C. limon, C. aurantifolia and C. limonia exhibited anti-inflammatory effects by reducing cell migration, cytokine production and protein extravasation induced by carrageenan. These effects were also obtained with similar amounts of pure limonene. It was also observed that C. aurantifolia induced myelotoxicity in mice. Anti-inflammatory effect of C. limon and C. limonia is probably due to their large quantities of limonene, while the myelotoxicity observed with C. aurantifolia is most likely due to the high concentration of citral. Our results indicate that these EOs from C. limon, C. aurantifolia and C. limonia have a significant anti-inflammatory effect; however, care should be taken with C. aurantifolia.