Punicalagin Inhibited Inflammation and Migration of Fibroblast-Like Synoviocytes Through NF-κB Pathway in the Experimental Study of Rheumatoid Arthritis.
Punicalagin Inhibited Inflammation and Migration of Fibroblast-Like Synoviocytes Through NF-κB Pathway in the Experimental Study of Rheumatoid Arthritis.
复制标题
安石榴苷在类风湿性关节炎的实验研究中通过 NF-κB 通路抑制成纤维细胞样滑膜细胞的炎症和迁移
DOI：
10.2147/jir.s302929
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发表时间：
2021
影响因子：
4.5
通讯作者：
Ouyang H
中科院分区：
文献类型：
--
作者：
Huang M;Wu K;Zeng S;Liu W;Cui T;Chen Z;Lin L;Chen D;Ouyang H
成纤维细胞样滑膜细胞（FLS）的侵袭性表型在类风湿关节炎（RA）滑膜炎和骨质破坏中起重要作用。石榴皮苷是从石榴汁中提取的一种天然多酚类化合物，具有抗氧化、抗炎和抗肿瘤等作用，有望成为治疗类风湿关节炎的有效药物。然而，关于其在RA中的作用的信息很少。目的探讨安石榴苷对类风湿关节炎滑膜炎症及骨破坏的影响。方法从RA患者滑膜组织中分离FLS。通过定量实时PCR评估mRNA水平。蛋白质印迹用于蛋白质水平测量。ELISA法检测促炎细胞因子和金属蛋白酶（MMPs）的分泌。Edu染色检测FLS的增殖情况。通过Boyden小室、伤口划痕试验和F-肌动蛋白染色体外评估细胞迁移。免疫荧光法检测核因子κ B（NF-κB）的胞内转位。通过使用胶原诱导的关节炎（CIA）小鼠测量安石榴苷的体内作用。结果石榴皮苷可显著降低TNF-α诱导的RA FLS细胞因子IL-1β、IL-6、IL-8和IL-17 A及MMP-1和MMP-13的表达。Punicalagin还抑制RA FLS的增殖和迁移。安石榴苷（50 mg/kg/d）可减轻CIA小鼠关节炎的严重程度和骨破坏，降低血清IL-6和TNF-α水平。进一步的机制研究表明，安石榴苷通过抑制IKK和IkBα的磷酸化，阻止65.结论安石榴苷可能通过调节NF-κB通路抑制FLS的炎症和迁移，从而成为缓解RA进展的天然治疗药物之一。
Background The aggressive phenotype of fibroblast-like synoviocytes (FLSs) is essential in the synovitis and bone destruction in rheumatoid arthritis (RA). Punicalagin is a natural polyphenol extracted in pomegranate juice, which possesses antioxidant, anti-inflammatory and anti-tumor properties suggesting it may be a potent drug for RA therapy. However, there is paucity of information on its effect in RA. Objective To investigate the effects of punicalagin on synovial inflammation and bone destruction in RA. Methods FLSs were isolated from synovial tissue of RA patients. The mRNA levels were evaluated by quantitative real-time PCR. Western blot was used for protein level measurements. The secretion of pro-inflammatory cytokines and metalloproteinases (MMPs) was detected by ELISA assays. Edu staining assays were carried out to investigate the proliferation of FLSs. Cell migration was assessed by Boyden chambers, wound scratch assays and F-actin staining in vitro. The intracellular translocation of nuclear factor kappa B (NF-κB) was investigated using immunofluorescence. The effects of punicalagin in vivo were measured by using collagen-induced arthritis (CIA) mice. Results Punicalagin treatments significantly reduced the TNF-α induced expressions of pro-inflammatory cytokines (IL-1β, IL-6, IL-8 and IL-17A) and MMPs (MMP-1 and MMP-13) of RA FLSs. Punicalagin also suppressed the proliferation and migration of RA FLSs. Moreover, punicalagin (50mg/kg/d) alleviated arthritis severity and bone destruction, and decreased serum IL-6 and TNF-α in CIA mice. Further mechanism studies indicated that punicalagin blocked NF-κB activation via suppressing phosphorylation of IKK and IkBα, and preventing the translocation of 65. Conclusion Our findings suggested that punicalagin might be one of natural therapeutic compounds for relieving RA progress via suppressing FLSs inflammation and migration through modulating NF-κB pathways.