Ginsenoside Metabolite Compound K Alleviates Adjuvant-Induced Arthritis by Suppressing T Cell Activation
Ginsenoside Metabolite Compound K Alleviates Adjuvant-Induced Arthritis by Suppressing T Cell Activation
复制标题
人参皂苷代谢物化合物 K 通过抑制 T 细胞活化减轻佐剂诱发的关节炎
DOI：
10.1007/s10753-014-9887-0
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发表时间：
2014-10-01
期刊：
影响因子：
5.1
通讯作者：
Wei, Wei
中科院分区：
文献类型：
--
作者：
Chen, Jingyu;Wu, Huaxun;Wei, Wei
人参皂苷代谢产物K(CK)是人参皂苷在肠道中被细菌降解的产物，具有抗炎等多种药理活性。类风湿关节炎(RA)是一种以多关节慢性滑膜炎症和关节损害为特征的炎症性和自身免疫性疾病。然而，CK对RA的作用尚不清楚。本研究旨在探讨CK在佐剂性关节炎(AA)中的作用及其与T细胞活化的关系。采用完全弗氏佐剂诱导AA大鼠模型。在大鼠关节炎发作后，给予CK(10、40和160 mg/kg)或MTX(0.5 mg/kg)。每3天评估一次关节炎指数和足肿胀程度，以评估关节炎的严重程度。取关节和脾进行病理组织学检查。用流式细胞仪检测T细胞亚群，包括CD4CD62L+(幼稚T细胞)、CD4CD25CD25+(活化T细胞)和CD4CD25Foxp3+细胞( + )和CD25CD25表达( + )。用3 H-TdR掺入法检测T细胞的增殖情况。采用双抗体夹心法测定IL-2水平。结果发现，CK能减轻关节炎指数和足肿胀，恢复关节和脾的组织病理学改变，下调活化T细胞的百分率，上调脾组织中的幼稚T细胞和Treg细胞。CK显著抑制T细胞活化(表现为T细胞增殖、CD25表达和IL-2产生)。综上所述，我们的结果提示CK通过抑制T细胞活化来减轻自身免疫性关节炎。
Ginsenoside metabolite compound K (CK) is the degradation product of ginsenosides in the intestine by bacteria and has many pharmacological activities including anti-inflammatory effects. Rheumatoid arthritis (RA) is an inflammatory and autoimmune disease characterized by chronic synovial inflammation and articular damage in multiple joints. However, the effect of CK on RA remains unclear. In this study, the effect of CK on adjuvant arthritis (AA) and the underlying mechanisms that focused on T cell activation were investigated. Complete Freund’s adjuvant was used to induce AA rats. After the onset of arthritis, rats were given CK (10, 40, and 160 mg/kg) or MTX (0.5 mg/kg). To evaluate the severity of arthritis, arthritis index and paw swelling were evaluated every 3 days. Histopathology of joint and spleen were assayed. Subsets of T cells including CD4 + CD62L+ (naïve T cells), CD4 + CD25+ (activated T cells), and CD4 + CD25 + Foxp3+ cells (Treg) and CD25 expression were assayed by flow cytometry. Proliferation of T cell was evaluated by3H-TdR. IL-2 level was assayed by ELISA. We found that CK attenuated arthritis index and paw swelling, restored the histopathological change of joint and spleen, downregulated the percentage of activated T cells, and upregulated naïve T cells and Treg cells in spleen. CK significantly suppressed T cell activation (as indicated by T cell proliferation, CD25 expression, and IL-2 production). In conclusion, our results suggest that CK alleviates autoimmune arthritis by suppressing T cell activation.