Tunisian Olea europaea L. leaf extract suppresses Freund's complete adjuvant-induced rheumatoid arthritis and lipopolysaccharide-induced inflammatory responses

Ethnopharmacological relevance: Olea europaea L. (olive) is traditionally used as a folk remedy and functional food in Europe and Mediterranean countries to treat inflammatory diseases. O. europaea contains phenolic compounds and have been reported to prevent cartilage degradation. However, the function and mechanism of O. europaea in rheumatoid arthritis are not known. Aim of the study: In this study, we aimed to examine anti-inflammatory and anti-arthritic effects of Tunisian O. europaea L. leaf ethanol extract (Oe-EE). Materials and methods: To do this, we employed an in vitro macrophage-like cell line and an in vivo Freund's complete adjuvant (AIA)-induced arthritis model. Levels of inflammatory genes and mediators were determined from in vivo samples. Results: The Oe-EE clearly reduced the production of the lipopolysaccharide-mediated inflammatory mediators, nitric oxide (NO) and prostaglandin E₂ (PGE₂), in RAW264.7 cells. The results of HPLC showed that Oe-EE contained many active compounds such as oleuropein and flavonoids. In AIA-treated rats, swelling of paws, pain, and cartilage degeneration were alleviated by oral Oe-EE administration. Correlating with in vitro data, PGE₂ production was significantly reduced in paw samples. Furthermore, the molecular mechanism of Oe-EE was dissected, and Oe-EE regulated the gene expression of interleukin (IL)-6, inducible NO synthase (iNOS), and MMPs and inflammatory signaling activation. Conclusion: Consequently, Oe-EE possesses anti-inflammatory and anti-rheumatic effects and is a potential effective treatment for rheumatoid arthritis.