Therapeutic Potential of Schinus terebinthifolia Raddi for Modulating Inflammatory and Immune Responses in MBSA-Induced Arthritis

Introduction: Schinus terebinthifolia Raddi (Anacardiaceae), popularly known as Aroeira, is widely recognized for its anti-inflammatory properties. Studies published by our research group have demonstrated that the extract from S. terebinthifolia (ST-70) exhibits anti-inflammatory activity in the zymosan-induced arthritis model [1]. Thus, this study aimed to evaluate the anti-arthritic potential of ST-70 in the Antigen-Induced Arthritis (AIA) model, analyzing the effects of treatment at two distinct stages: at 24 hours (early phase) and 7 days (late phase). 

Methodology: S. terebinthifolia leaves were macerated with 70% ethanol to obtain ST-70. C57BL/6 mice were immunized (s.c.) with an emulsion of methylated bovine serum albumin (mBSA) and Complete Freund's Adjuvant (CFA). On the 21st day post-immunization, arthritis was induced by intra-articular (i.a.) challenge with mBSA, and two treatment protocols were evaluated. In the single-dose pre-treatment protocol, ST-70 (25–100 mg/kg, p.o.) was administered 1 h before the mBSA challenge, and synovial fluid washes were collected 24 h later for leukocyte counting. In the repeated-treatment protocol, ST-70 (25–100 mg/kg, p.o.) or methotrexate (MTX, 1.5 mg/kg, i.p.) was administered on the day of challenge and daily for the subsequent 6 days. CEUA: LW-15/2023. 

Results: Treatment with ST-70 (100 mg/kg) significantly reduced joint swelling at both stages evaluated. In the early phase (24 h), the treatment reduced leukocyte infiltration (52.05%) and neutrophils (20.31%) in the synovial cavity, as well as inflammatory mediators in the synovial wash. In the late phase (7 days), it reduced peripheral leukocytosis, neutrophil infiltration, and the cellularity of the inguinal lymph nodes. 

Conclusion: The ST-70 modulates mBSA-induced arthritis by reducing neutrophil recruitment and leukocyte accumulation in the blood and lymph nodes, highlighting its potential as a novel therapeutic approach for arthritis.