Anti-inflammatory effect of Schinus terebinthifolius Raddi hydroalcoholic extract on neutrophil migration in zymosan-induced arthritis

Ethnopharmacological relevance: Schinus terebinthifolius is a species of plant from the Anacardiaceae family, which can be found in different regions of Brazil. Schinus is popularly known as aroeirinha, aroeira-vermelha, or Brazilian pepper. In folk medicine, S. terebinthifolius is used for several disorders, including inflammatory conditions, skin wounds, mucosal membrane ulcers, respiratory problems, gout, tumors, diarrhea and arthritis. According to chemical analyses, gallic acid, methyl gallate and pentagalloylglucose are the main components of hydroalcoholic extracts from S. terebinthifolius leaves. In the present study, we demonstrated the ability of a hydroalcoholic extract to inhibit cell migration in arthritis and investigated the mechanisms underlying this phenomenon. Materials and methods: The anti-inflammatory effect of S. terebinthifolius hydroalcoholic leaf extract (ST-70) was investigated in a zymosan-induced experimental model of inflammation. Male Swiss and C57B1/6 mice received zymosan (100 mu g/cavity) via intra-thoracic (i.t.) or intra-articular (i.a.) injection after oral pre-treatment with ST-70. The direct action of ST-70 on neutrophils was evaluated via chemotaxis. Results: ST-70 exhibited a dose-dependent effect in the pleurisy model. The median effective dose (ED50) was 100 mg/kg, which inhibited 70% of neutrophil accumulation when compared with the control group. ST-70 reduced joint diameter and neutrophil influx for synovial tissues at 6 h and 24 h in zymosan-induced arthritis. Additionally, ST-70 inhibited synovial interleukin (IL)-6, IL-1 beta, keratinocyte-derived chemokine (CXCL1/KC) and Tumor Necrosis Factor (TNF)-alpha production at 6 h and CXCL1/KC and IL-1 beta production at 24 h. The direct activity of ST-70 on neutrophils was observed via the impairment of CXCL1/KC-induced chemotaxis in neutrophils. Oral administration of ST-70 did not induce gastric damage. Daily administration for twenty days did not kill any animals. In contrast, similar administrations of diclofenac induced gastric damage and killed all animals by the fifth day. Conclusions: Our results demonstrated significant anti-inflammatory effects of ST-70, suggesting a putative use of this herb for the development of phytomedicines to treat inflammatory diseases, such as joint inflammation. (C) 2015 Elsevier Ireland Ltd. All rights reserved.