Piperin is the active compound of black pepper (Piper nigrum). From the piperine was obtained the molecule of the piperic acid (PAC). The objective of this study was to evaluate the antinociceptive and anti-inflammatory of the compound. The antinociceptive effects of PAC were evaluated by abdominal writhing, formalin, capsaicin and tail-flick tests; while the anti-inflammatory effects were evaluated by paw oedema and air pouch tests, and in vitro COX inhibition assay. The possible action mechanism of PAC was evaluated using naloxone, L-NAME, glibenclamide and atropine in tail flick test and by Cholinesterase activity assay and production of TNF-α and IL-1β. PAC significantly reduced the nociceptive effects induced by acetic acid or formalin in mice. PAC also demonstrated an antinociceptive effect in the tail-flick model. The muscarinic receptor antagonist, atropine reduced the antinociceptive effect of PAC in the tail-flick model. PAC was able to inhibit capsaicin-induced nociception, showing involvement of TRPV1. The compound did not alter the motor capacity of the animals, not interfering in the nociceptive response. PAC also showed anti- inflammatory activity by inhibiting the formation of carrageenan-induced paw oedema, leukocyte migration, and cytokine production / release. Atropine reduced the activity of PAC on leukocyte migration, and cytokine production. The compound showed to be able to reduce the cytokine production stimulated by capsaicin. PAC inhibited the COX activity. The results presented suggest that the possible cholinomimetic action and vanilloid agonist of the piperic acid may be responsible by antinociceptive and anti- inflammatory effects; these effects are devoid of toxicity.

The development of analgesic drugs is still a necessity due to the inefficiency of the current treatments for some pathological conditions and also due to the adverse effects produced by these drugs. The aim of this study was to deepen the pharmacological study of two new hybrids NSAIDs tetrahydropyran derivatives, regarding their antinociceptive effects on acute pain in mice. Male swiss mice were evaluated in the acetic acid-induced abdominal writhing, formalin, tail-flick, open-field, glutamate-and capsaicin-induced paw licking tests, and in vitro Cox inhibition assay, besides the acute toxicological evaluation. The compounds had an effect on the acetic acid-induced abdominal writhing, formalin (both phases), and tail-flick tests. In the study of the mechanism of action was observed reversion of the antinociceptive effect of the compounds from the previous administration of naloxone, L-NAME (L-nitro-arginine methyl ester), ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one), glibenclamide, and nor-binaltorphimine, by the intrathecal and intraperitoneal routes. The prior administration of MK-801 suggests that the modulation of NMDA receptor contributes to the antinociceptive effect of compounds. In summary, hybrid compounds presented central antinociceptive effect, demonstrating participation of the NO-cGMP-K + ATP pathway, j-opioid, and NMDA receptors. In addition, the compounds showed inhibition of cyclo-oxygenase enzymes and adverse effects were not observed with dose 300 times greater than the dose used experimentally.

Ouratea species are used for the treatment of inflammation-related diseases such as rheumatism and arthritic disorders. The Ouratea genus is a rich source of flavonoids and bioflavonoids and for this reason we evaluated the effects of the biflavonoid fractions from the leaves of O. hexasperma (OHME) and O. ferruginea (OFME) in the in vivo model of complete Freund’s adjuvant (CFA)-induced arthritis and in the in vitro model of oxidative stress and cellular viability. The CFA-induced arthritis model in rats was followed by paw volume, articular incapacitation and Randall-selitto models, as well as quantification of cytokines and serum C-terminal telopeptide of type I collagen levels. OHME and OFME demonstrated antinociceptive and anti-inflammatory activities, as well as improvement in articular incapacity and reduction in levels of interleukin 1β (IL-1β), IL-6, tumor necrosis factor α, and type 1 collagen, and increased cell viability. No adverse effects were observed. The results suggest that OHME and OFME can reduce inflammation and bone resorption besides their antioxidant action.

Objective: The species Chrysobalanus icaco L., popularly known as abajurú, abajeru, has frequently been associated with antiangiogenic, anti-inflammatory and antirheumatic effects. The 2α-3β-6β-23-tetrahydro-olean-12-en-28-oic acid (THOA) was isolated from the methanolic extract of Chrysobalanus icaco leaves. Thus, the aim of the study was to evaluate the antinociceptive and anti-inflammatory activities of THOA.Methods: Acetic acid-induced abdominal writhing, formalin, von frey and open field tests were performed in mice. The number of writhes, licking time, mechanical threshold and walked squares by animals were the evaluation parameters applied, respectively. In addition, quantification of IL-1β and TNF-α were also performed. The THOA was administered orally at doses of 1–10 mg/kg in male mice. In addition, water, vehicle, morphine (5.01 mg/kg), acetylsalicylic acid (100 mg/kg), and dexamethasone (2.25 mg/kg) were administered.Results: The THOA showed effect with 5 and 10 mg/kg in the acute pain induced by acetic acid (49% and 62% contortion inhibition), carrageenan (150% and 188% increase in mechanical threshold) and formalin (36% and 60% licking inhibition), respectively. These results indicate an inhibition of hyper nociception, while the reduction in the production of cytokines (TNF-α inhibition–64% and 88%; IL-1β inhibition–48% and 55%, respectively) confirmed the inflammatory inhibition by carrageenan. The THOA did not induce motor impairment. The THOA was not toxic after oral administration (LD50>50 mg/kg).Conclusion: These data provide initial evidence that THOA decreases the inflammatory hyper nociception probably by inhibition of IL-1β and TNF-α production, proving to be effective in reducing pain and inflammation.