The aim of this study was to evaluate the effect of ylang-ylang (Cananga odorata) essential oil (YEO) on models of experimental arthritis, persistent inflammation, and nociception in mice. YEO treatment at doses of 100 and 200 mg/kg reduced the infiltration of leukocytes into the joint cavities of mice submitted to zymosan-induced arthritis 6 h and 7 days after arthritis induction. At these doses, YEO treatment reduced the formation of joint edema 4 and 6 h after arthritis induction, and at a dose of 200 mg/kg, YEO treatment reduced mechanical hyperalgesia 3 and 4 h after arthritis induction. At the dose of 200 mg/kg, YEO treatment reduced interleukin-6 (IL-6) levels and cartilage destruction in the zymosan-induced arthritis model, and reduced edema formation and mechanical hyperalgesia in the model of persistent inflammation (21 days) induced by complete Freund’s adjuvant (CFA) in mice. YEO treatment at a dose of 200 mg/kg reduced the nociceptive response in experimental models of nociception induced by acetic acid and formalin. The YEO treatment reduced inflammatory parameters in the experimental arthritis model, and presented antiarthritic, anti-hyperalgesic, antinociceptive, and anti-inflammatory properties.

Leishmaniases are neglected diseases with limited therapeutic options. Diffuse cutaneous leishmaniasis can occur in Brazil due to Leishmania amazonensis. This study details the antileishmanial activity and cytotoxicity of complexes of sodium usnate (SAU) with lanthanide ions ([LnL₃ (H₂O)_x] (Ln = La(III), Nd(III), Gd(III), Tb(III), Eu(III) and Sm(III); L = SAU). All lanthanide complexes were highly active and more potent than SAU against L. amazonensis promastigotes and intracellular amastigotes (Pro: IC₅₀ < 1.50 μM; Ama: IC₅₀ < 7.52 μM). EuL₃·3H₂O and NdL₃·3H₂O were the most selective and effective on intracellular amastigotes, with a selectivity index of approximately 7.0. In silico predictions showed no evidence of mutagenicity, tumorigenicity or irritation for all complexes. Treatment with EuL₃·3H₂O triggered NO release even at the lowest concentration, indicating NO production as a mechanism of action against the parasite. Incubating promastigotes with the lanthanide complexes, particularly with SmL₃·4H₂O and GdL₃·3H₂O, led to a change in the mitochondrial membrane potential, indicating the ability of these complexes to target this essential organelle. The same complexes caused cell death through cell membrane disruption, but their relationship with early or late apoptotic processes remains unclear. Thus, the inclusion of lanthanide ions in SAU improves selectivity with a promising mechanism of action targeting the mitochondria.

Handroanthus heptaphyllus (Vell.) Mattos (Bignociaceae), popularly known in Brazil as "ipê-roxo" or "lapacho", is native to the Pantanal biome (Brazil). Its bark is traditionally used to treat inflammation, yet no scientific evidence currently supports this ethnomedicinal use. This study aimed to characterize the phytochemical profile of the hydroethanolic extract of H. heptaphyllus bark (HhHE), to evaluate its anti-inflammatory potential, and investigate its toxicity. From HhHE, several compounds were annotated, including glycosylated iridoids and phenolics. This extract did not present cytotoxicity, and significantly reduced the in vitro neutrophil chemotaxis and phagocytosis activity. The HhHE treatment reduced mast cell degranulation, carrageenan-induced edema formation and hyperalgesia. In addition, it reduced leukocyte recruitment, pro-inflammatory cytokines, such as tumor necrosis factor (TNF), and interleukin-6 (IL-6), and nitric oxide (NO) levels in zymosan-induced peritonitis model. The HhHE treatment also inhibited nociceptive responses in the inflammatory phase of the formalin, and acetic acid-induced abdominal writhing test, without impairing locomotion. HhHE has demonstrated significant anti-inflammatory and antinociceptive effects, possibly through the modulation of leukocyte activity and the decrease in the levels of the inflammatory mediators, such as IL-6, TNF, and NO, corroborating its traditional use and indicating its therapeutic potential in the management of inflammation and inflammatory pain.

Delta-3-carene (CAR), a monoterpene derived from plant essential oils, exhibits promising biological properties, including anti-inflammatory, antioxidative, anxiolytic, and antimicrobial activities. Therefore, this study aimed to investigate the anti-inflammatory effects of CAR by analyzing the activity of this terpene on leukocyte activation through the evaluation of cell migration in in vitro and in vivo models. Cell viability analysis demonstrated that CAR (3, 10, 30, and 90 μg/mL) exerted no cytotoxic effects and significantly reduced in vitro neutrophil chemotaxis toward N-formylmethionyl-leucyl-phenylalanine (fMLP). Furthermore, CAR decreased phagocytosis in zymosan-stimulated neutrophils in vitro. In Swiss mice, oral CAR treatment, at doses of 25, 50, and 100 mg/kg, reduced inflammatory and antinociceptive parameters in zymosan-induced peritonitis, carrageenan-induced paw edema and mechanical hyperalgesia, and nociception induced by acetic acid and formalin models. In the persistent inflammation model (for 21 days) induced by complete Freund’s adjuvant (CFA), daily CAR treatment (50 mg/kg) reduced paw edema and mechanical hyperalgesia in all evaluated times at 6, 11, 16, and 21 days after CFA-induced inflammation. In conclusion, our data demonstrated that CAR modifies acute and chronic inflammatory responses, highlighting its potential therapeutic application in managing inflammation and pain.