肉桂醛通过调节 Jak/Stat 通路抑制人滑膜细胞炎症反应并改善胶原诱导的大鼠关节炎。
Cinnamaldehyde Inhibits Inflammation of Human Synoviocyte Cells Through Regulation of Jak/Stat Pathway and Ameliorates Collagen-Induced Arthritis in Rats.
机构信息
Translational Medicine R&D Center, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China (W.-X.C., S.Z., X.-B.M., P.Z., L.Q., X.-L.W.); University of Chinese Academy of Sciences, Beijing, China (W.-X.C., P.Z., X.-L.W.); Musculoskeletal Research Laboratory of Department of Orthopaedics and Traumatology and Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory of Li Ka Shing Institute of Health, The Chinese University of Hong Kong, Hong Kong SAR, China (N.-Y.Z., L.Q., X.-L.W.); and Center for Research and Technology of Precision Medicine, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, Guangdong, China (S.Z., Y.W.).
Translational Medicine R&D Center, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China (W.-X.C., S.Z., X.-B.M., P.Z., L.Q., X.-L.W.); University of Chinese Academy of Sciences, Beijing, China (W.-X.C., P.Z., X.-L.W.); Musculoskeletal Research Laboratory of Department of Orthopaedics and Traumatology and Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory of Li Ka Shing Institute of Health, The Chinese University of Hong Kong, Hong Kong SAR, China (N.-Y.Z., L.Q., X.-L.W.); and Center for Research and Technology of Precision Medicine, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, Guangdong, China (S.Z., Y.W.)
出版信息
J Pharmacol Exp Ther. 2020 May;373(2):302-310. doi: 10.1124/jpet.119.262907. Epub 2020 Feb 6.
Cinnamaldehyde (Cin), a bioactive cinnamon essential oil from traditional Chinese medicine herb , has been reported to have multipharmacological activities including anti-inflammation. However, its role and molecular mechanism of anti-inflammatory activity in musculoskeletal tissues remains unclear. Here, we first investigated the effects and molecular mechanisms of Cin in human synoviocyte cells. Then in vivo therapeutic effect of Cin on collagen-induced arthritis (CIA) also studied. Cell Counting Kit CCK-8 assay was performed to evaluate the cell cytotoxicity. Proinflammatory cytokine expression was evaluated using quantitative polymerase chain reaction and ELISA. Protein expression was measured by western blotting. The in vivo effect of Cin (75 mg/kg per day) was evaluated in rats with CIA by gavage administration. Disease progression was assessed by clinical scoring, radiographic, and histologic examinations. Cin significantly inhibited interleukin (IL)-1-induced IL-6, IL-8, and tumor necrosis factor- release from human synoviocyte cells. The molecular analysis revealed that Cin impaired IL-6-induced activation of Janus kinase 2 (JAK2), signal transducer and activator of transcription 1 (STAT1), and STAT3 signaling pathway by inhibiting the phosphorylation of JAK2, STAT1, and STAT3, without affecting NF-B pathway. Cin reduced collagen-induced swollen paw volume of arthritic rats. The anti-inflammation effects of Cin were associated with decreased severity of arthritis, joint swelling, and reduced bone erosion and destruction. Furthermore, serum IL-6 level was decreased when Cin administered therapeutically to CIA rats. Cin suppresses IL-1-induced inflammation in synoviocytes through the JAK/STAT pathway and alleviated collagen-induced arthritis in rats. These data indicated that Cin might be a potential traditional Chinese medicine-derived, disease-modifying, antirheumatic herbal drug. SIGNIFICANCE STATEMENT: In this study, we found that cinnamaldehyde (Cin) suppressed proinflammatory cytokines secretion in rheumatology arthritis synoviocyte cells by Janus kinase/signal transducer and activator of transcription pathway. The in vivo results showed that Cin ameliorated collagen-induced arthritis in rats. These findings indicate that Cin is a potential traditional Chinese medicine-derived, disease-modifying, antirheumatic herbal drug.
肉桂醛（Cin）是一种来自传统中药肉桂的生物活性精油，已被报道具有多种药理活性，包括抗炎作用。然而，其在肌肉骨骼组织中的抗炎活性的作用和分子机制尚不清楚。在这里，我们首先研究了 Cin 在人滑膜细胞中的作用和分子机制。然后还研究了 Cin 在胶原诱导性关节炎（CIA）中的体内治疗效果。通过细胞计数试剂盒（CCK-8）测定评估细胞毒性。通过定量聚合酶链反应和 ELISA 评估促炎细胞因子的表达。通过 Western blot 测定蛋白表达。通过灌胃给予 Cin（每天 75mg/kg）在 CIA 大鼠中评估体内作用。通过临床评分、放射照相和组织学检查评估疾病进展。Cin 显著抑制白细胞介素（IL）-1 诱导的人滑膜细胞中白细胞介素（IL）-6、IL-8 和肿瘤坏死因子-α的释放。分子分析表明，Cin 通过抑制 JAK2、STAT1 和 STAT3 的磷酸化来损害 IL-6 诱导的 JAK2、信号转导和转录激活因子 1（STAT1）和 STAT3 信号通路的激活，而不影响 NF-B 通路。Cin 减少胶原诱导的关节炎大鼠肿胀的爪子体积。Cin 的抗炎作用与关节炎严重程度、关节肿胀和骨侵蚀和破坏减少有关。此外，当 Cin 给 CIA 大鼠进行治疗时，血清中 IL-6 水平降低。Cin 通过 JAK/STAT 通路抑制滑膜细胞中 IL-1 诱导的炎症，并减轻胶原诱导性关节炎大鼠的关节炎。这些数据表明，Cin 可能是一种有潜力的传统中药衍生的、疾病修饰的、抗风湿草药。意义陈述：在这项研究中，我们发现肉桂醛（Cin）通过 Janus 激酶/信号转导和转录激活因子通路抑制风湿病关节炎滑膜细胞中促炎细胞因子的分泌。体内结果表明，Cin 改善了胶原诱导性关节炎大鼠的病情。这些发现表明 Cin 是一种有潜力的传统中药衍生的、疾病修饰的、抗风湿草药。
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