Terpinolene inhibits acute responses triggered by different inflammatory in vivo models of mouse

The aim of this work was evaluate the effects of terpinolene on acute inflammatory responses in mice. In vivo preclinical research using different inflammatory agents to induce acute responses and evaluate the effects of terpinolene in orally treated mice. The acute inflammatory responses were induced by injecting phlogistic agents in the mice paw to observe the development of pain responses (formalin test) or edema (carrageenan, dextran, histamine, arachidonic acid, and prostaglandin). The antiedematogenic activity was also evaluated using a croton oil-induced ear edema model. Finally, cotton pellet-induced granuloma was used to carry out a pre-liminary evaluation of terpinolene in a chronic inflammatory model. Topically administered terpinolene (5, 10, and 20 mg/mL) significantly inhibited ear edema development (by 33.82%, 29.63%, and 33,30%, respectively). Following an oral administration, only the highest dose of the monoterpene (200 mg/kg) reduced the licking time of the formalin test in both phases 1 (73.55%) and 2 (96.61%). The carrageenan-induced edema signifi-cantly inhibited over time following the oral administration of terpinolene at 50 mg/kg (T1: 47.74%, T2: 54.67%, T3: 48.63%, and T4: 62.99%), 100 mg/kg (T1: 72.86%, T2: 71.03%, T3: 48.63%, and T4: 57.83%), and 200 mg/kg (T1: 43.22%, T2: 34.11%, T3: 36.47%, and T4: 45.20%). On the other hand, only the dose of 200 mg/ kg) caused a significant reduction of the dextran-induced paw edema (T1: 51.18%, T2: 60%, T3: 50.92%, and T4: 65.15%). Regarding the participation of inflammatory pathways, the monoterpene (200 mg/kg, p.o.) had little impact on histamine-induced edema, while the edema induced by arachidonic acid was significantly reduced at all time-points (T1: 37.04%, T2: 24.32%, and T3: 35.13%, and T4: 35.53%), which was corroborated by the observation that the compound inhibited the response triggered by prostaglandin E2 (PGE2), suggesting inter-ference with downstream signaling cascades. Finally, terpinolene (200 mg/kg, p.o.) reduced both the weight (21.43%) and total protein content (36.21%) of the cotton pellet-induced granuloma, indicating an anti-inflammatory activity in this chronic model. Terpinolene inhibited acute inflammatory responses and reduced granuloma development in vivo, possibly by interfering with the tissue changes orchestrated by inflammatory mediators such as histamine and PGE2. However, the molecular mechanisms underlying this pharmacological observation need to be confirmed by further research.