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雷公藤红素和姜黄素通过抑制 IL-17/NF-κB 信号通路来改善细胞增殖并诱导细胞凋亡,对类风湿关节炎发挥协同作用。

A synergistic effect of triptolide and curcumin on rheumatoid arthritis by improving cell proliferation and inducing cell apoptosis via inhibition of the IL-17/NF-κB signaling pathway.

机构信息

Department of Hematology and Rheumatology, The Affiliated Hospital of Putian University, Fujian Province, China; School of Basic Medicine, Putian University, Fujian Province, China.

Pharmaceutical and Medical Technology College, Putian University, Fujian Province, China.

出版信息

Int Immunopharmacol. 2024 Dec 5;142(Pt A):112953. doi: 10.1016/j.intimp.2024.112953. Epub 2024 Sep 2.

Abstract

Rheumatoid arthritis (RA) is a chronic, progressive, systemic autoimmune disease. While triptolide (TPL) and curcumin (CUR) are known to have multiple beneficial effects on RA, the combined effect of TPL and CUR remains unexplored. This study aimed to investigate their synergistic effect on cell proliferation and apoptosis via the IL-17/NF-κB signaling pathway. The collagen-induced arthritis (CIA) rat model was established, showing severe joint and synovial damage compared to normal rats. Treatment with TPL and CUR reduced the severity of RA in the CIA rat model and alleviated serum inflammatory cytokines, such as rheumatoid factor, IL-17, TNF-α, IL-1β, and IL-6. The elevated levels of IL-17 and NF-κB in CIA rats were also inhibited, and the resistant apoptosis was aggravated by TPL and CUR. In vitro, the improvement of cell proliferation and induction of apoptosis were observed in LPS-stimulated MH7A cells treated with TPL and CUR, associated with the inhibition of the IL-17/NF-κB signaling pathway. Taken together, a synergistic effect of TPL and CUR on RA may involve relieving symptoms, improving excessive proliferation, inducing apoptosis resistance, and inhibiting the IL-17/NF-κB signaling pathway.

摘要

类风湿性关节炎(RA)是一种慢性、进行性、系统性自身免疫性疾病。虽然雷公藤内酯醇(TPL)和姜黄素(CUR)已知对 RA 有多种有益作用,但 TPL 和 CUR 的联合作用仍未被探索。本研究旨在通过 IL-17/NF-κB 信号通路研究它们对细胞增殖和凋亡的协同作用。建立胶原诱导性关节炎(CIA)大鼠模型,与正常大鼠相比,该模型表现出严重的关节和滑膜损伤。TPL 和 CUR 治疗减轻了 CIA 大鼠模型中 RA 的严重程度,并缓解了血清炎症细胞因子,如类风湿因子、IL-17、TNF-α、IL-1β 和 IL-6。CIA 大鼠中升高的 IL-17 和 NF-κB 也被抑制,TPL 和 CUR 加重了抵抗性凋亡。在体外,用 TPL 和 CUR 处理 LPS 刺激的 MH7A 细胞观察到细胞增殖的改善和凋亡的诱导,这与 IL-17/NF-κB 信号通路的抑制有关。综上所述,TPL 和 CUR 对 RA 的协同作用可能涉及缓解症状、改善过度增殖、诱导凋亡抵抗以及抑制 IL-17/NF-κB 信号通路。

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