Participation of Cytokines, Opioid, and Serotoninergic Systems on Antinociceptive and Anti‑inflammatory Activities of Simira grazielae Peixoto (Rubiaceae)

Background: Simira grazielae P. is widely found at Brazil. S. grazielae have been used to treat pain and inflammation in the Northeast of Brazil. Objective: This study investigated the mechanisms of the extract and partitions using pharmacological techniques in mice. Materials and Methods: Male Swiss mice (20–22 g) were used in models of pain (acetic acid‑induced abdominal writhing, formalin, and tail‑flick tests) and inflammation (edema paw and air pouch tests) as well as in model for the evaluation of motor activity (open field test). Furthermore, we evaluate the probable action mechanism of S. grazielae using naloxone, L‑nitro‑arginine methyl ester, L‑arginine, glibenclamide, atropine, 4‑chloro‑DL‑phenylalanine, and ondansetron in tail‑flick test. The cytokines production was also evaluated. The methanolic extract from the S. grazielae and its partitions were administered orally at doses of 10–100 mg/kg. Results: Methanolic extract from the wood of S. grazielae (SGM) and its partitions showed antinociceptive properties in models of acute pain (SGM and ethyl acetate partition [SGMAc]) as well as in models of inflammation (dichloromethane partition [SGMD]). Prior administration of ondansetron and naloxone reduced the antinociceptive effect of SGMAc. SGMD reduced the production of tumor necrosis factor‑α (TNF‑α) induced by carrageenan. Conclusion: The results show that the anti‑inflammatory activity showed by SGMD involves to reduction of the TNF‑α, and the antinociceptive activity showed by SGMAc has relation to participation of the serotoninergic receptors and opioid system. These evidence justify the popular therapeutic use of this species in the control of pain and inflammation.