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薯蓣皂苷元,一种从穿山龙中分离得到的甾体皂苷,通过抑制 Th17 细胞应答来减轻胶原诱导性关节炎。

Dioscin, a Steroidal Saponin Isolated from Dioscorea nipponica, Attenuates Collagen-Induced Arthritis by Inhibiting Th17 Cell Response.

机构信息

* Department of Rheumatology, Nantong Hospital Affiliated to Nanjing, University of Traditional Chinese Medicine, Nantong, Jiangsu 226001, P. R. China.

† The No. 1 Affiliated Hospital of Yunnan, University of Traditional Chinese Medicine, Kunming 650021, P. R. China.

出版信息

Am J Chin Med. 2019;47(2):423-437. doi: 10.1142/S0192415X19500216. Epub 2019 Mar 4.

DOI:10.1142/S0192415X19500216
PMID:30827153
Abstract

Dioscin, a steroidal saponin isolated from Dioscorea nipponica Makino, has previously been shown to possess antiarthritic effects. However, the underlying mechanism is still elusive. Herein, we investigated the therapeutic effects of dioscin on collagen-induced arthritis (CIA) in DBA/1 mice and related mechanism. Cytokine production in CII-specific immune responses were measured by enzyme-linked immunosorbent assay (ELISA); Th17 cell-related gene expression, including IL-17A, ROR and IL-23p19, were detected by qPCR analysis; Surface marker, T regulatory (Treg) cells and intracellular cytokines (IL-17A and IFN- ) were evaluated by flow cytometry. We performed Th17 cell differentiation assay in vitro. Results showed that, in vivo, dioscin treatment significantly reduced the severity of CIA, which was accompanied by decreased Th17 response, but not Th1 and Treg response; dioscin-treated mice also showed lower percentage of CD11b Gr-1 neutrophils; In vitro, dioscin treatment suppressed the differentiation of naive CD4 T cells into Th17 cell and decreased IL-17A production. Collectively, our results indicate that dioscin exerts antiarthritic effects by inhibiting Th17 cell immune response.

摘要

薯蓣皂苷元是从穿山龙中分离得到的一种甾体皂苷,先前已被证明具有抗关节炎作用。然而,其潜在的机制仍不清楚。在此,我们研究了薯蓣皂苷元对 DBA/1 小鼠胶原诱导性关节炎(CIA)的治疗作用及相关机制。采用酶联免疫吸附试验(ELISA)检测 CII 特异性免疫反应中的细胞因子产生;通过 qPCR 分析检测 Th17 细胞相关基因表达,包括 IL-17A、RORγt 和 IL-23p19;通过流式细胞术评估表面标志物、调节性 T(Treg)细胞和细胞内细胞因子(IL-17A 和 IFN-γ)。我们进行了体外 Th17 细胞分化实验。结果表明,体内给予薯蓣皂苷元治疗可显著减轻 CIA 的严重程度,伴随 Th17 反应降低,但 Th1 和 Treg 反应不受影响;薯蓣皂苷元治疗的小鼠还显示出较低的 CD11b Gr-1 中性粒细胞比例;体外,薯蓣皂苷元治疗可抑制幼稚 CD4+T 细胞向 Th17 细胞分化,并减少 IL-17A 的产生。综上所述,我们的结果表明薯蓣皂苷元通过抑制 Th17 细胞免疫反应发挥抗关节炎作用。

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