Clove oil-derived β-caryophyllene carried in a self-nanoemulsifying drug delivery system improves adjuvant-induced arthritis in rats.

OBJECTIVES

β-Caryophyllene (β-Cary) exhibits anti-inflammatory and antioxidant activities. It can be obtained from clove oil, which is rich in eugenol; following eugenol removal, β-Cary can be isolated as the major constituent. However, the high lipophilicity of β-Cary limits its oral bioavailability. The present study investigated the anti-arthritic effects of β-Cary formulated in a self-nanoemulsifying drug delivery system (β-SNEDDS) in Holtzman rats with complete Freund's adjuvant-induced arthritis, emphasizing articular inflammation and systemic oxidative stress.

METHODS

Healthy and adjuvant-induced arthritic rats received oral β-Cary or β-SNEDDS (50 or 100 mg/kg). Treatments were administered by oral gavage for 18 days after arthritis induction. Paw oedema, arthritis severity score, and articular leucocyte infiltration were assessed. Cartilage and growth plate integrity were evaluated by histological and histomorphometric analyses of the knee joint. Oxidative stress parameters, mRNA expression of cytokines and cachexia-related MuRF1, plasma markers of liver injury, and hepatic gluconeogenesis were also evaluated.

KEY FINDINGS: β-SNEDDS exhibited greater anti-arthritic efficacy than non-formulated β-Cary. β-SNEDDS (100 mg/kg) reduced paw oedema and arthritis score while preserving cartilage structure, and downregulated TNF-α, IL-1β, IL-6, and MuRF1 mRNA expression in periarticular skeletal muscle. In addition, β-SNEDDS restored most oxidative stress parameters altered by arthritis. Although free β-Cary improved selected oxidative stress parameters, β-SNEDDS showed a broader protective profile. Neither β-Cary nor β-SNEDDS induced hepatotoxicity, as demonstrated by unchanged plasma markers of liver injury and hepatic gluconeogenesis in healthy rats.

CONCLUSIONS

Nanoemulsification enhanced the oral anti-arthritic efficacy and antioxidant activity of β-caryophyllene, supporting β-SNEDDS as a promising strategy for rheumatoid arthritis.