Rheumatoid arthritis (RA) is an autoimmune disorder, in which imbalance in synthesis and production of inflammatory cytokines promotes cartilage and bone destruction. Out of the numerous factors contributing to RA prognosis, the transcription factor NF-kBp65 and p38 mitogen-activated protein kinase (p38MAPK) signaling module has been well implicated as a key regulator of inflammation and downstream signaling events in RA. Stigmasterol (STG) is a natural plant based product exhibiting anti-inflammatory activity, however, the mechanism through which it exhibits anti-inflammatory activity has not been completely understood. The current study aimed to understand the mechanisms underlying the anti-inflammatory effect of STG in the treatment of RA in collagen-induced arthritic (CIA) model of arthritis. Our results showed that STG improved the clinical severity in CIA rats compared to control. The therapeutic effects were related with reduced joint destruction and improved histological alterations. Furthermore, treatment of STG also significantly suppresses the expression of proinflammatory mediators (TNF-α, IL-6, IL-1β, iNOS and COX-2) and increases the expression of anti-inflammatory cytokine (IL-10) through down-regulating the expression of NF-kBp65 (inhibiting p-IKB-α activation) and p38MAPK in joints. In agreement with our results, we can suggest that high therapeutic efficacy of STG against CIA induced inflammation in rats are attributed through the suppressing proinflammatory cytokines.

类风湿关节炎（RA）是一种自身免疫性疾病，其中炎症细胞因子的合成和产生失衡会促进软骨和骨破坏。在导致RA预后的众多因素中，转录因子NF-kBp65和p38丝裂原活化蛋白激酶（p38MAPK）信号传导模块已被认为是RA中炎症和下游信号传导事件的关键调节因子。Stigmasterol（STG）是天然植物基产品，具有抗炎活性，但是，其抗炎活性的机理尚未完全了解。当前的研究旨在了解胶原诱导的关节炎（CIA）模型中STG在RA治疗中的抗炎作用的潜在机制。我们的结果表明，与对照组相比，STG改善了CIA大鼠的临床严重程度。治疗效果与减少关节破坏和改善组织学改变有关。此外，STG的治疗还可以显着抑制促炎性介质（TNF-α，IL-6，IL-1β，iNOS和COX-2）的表达，并通过下调抗炎细胞因子（IL-10）的表达。 NF-kBp65（抑制p-IKB-α激活）和p38MAPK在关节中的表达。与我们的结果相吻合，我们可以认为STG对CIA诱导的大鼠炎症的高治疗功效归因于抑制促炎细胞因子。此外，STG的治疗还可以显着抑制促炎性介质（TNF-α，IL-6，IL-1β，iNOS和COX-2）的表达，并通过下调抗炎细胞因子（IL-10）的表达。 NF-kBp65（抑制p-IKB-α激活）和p38MAPK在关节中的表达。与我们的结果相吻合，我们可以认为STG对CIA诱导的大鼠炎症的高治疗功效归因于抑制促炎细胞因子。此外，STG的治疗还可以显着抑制促炎性介质（TNF-α，IL-6，IL-1β，iNOS和COX-2）的表达，并通过下调抗炎细胞因子（IL-10）的表达。 NF-kBp65（抑制p-IKB-α激活）和p38MAPK在关节中的表达。与我们的结果相吻合，我们可以认为STG对CIA诱导的大鼠炎症的高治疗功效归因于抑制促炎细胞因子。