Delta-3-Carene Presented Anti-Inflammatory and Antinociceptive Properties by Modulating Leukocyte Activation in the Experimental Inflammatory Response In Vitro and In Vivo

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.