Antcin K Inhibits TNF-α, IL-1β and IL-8 Expression in Synovial Fibroblasts and Ameliorates Cartilage Degradation: Implications for the Treatment of Rheumatoid Arthritis.
Antcin K Inhibits TNF-α, IL-1β and IL-8 Expression in Synovial Fibroblasts and Ameliorates Cartilage Degradation: Implications for the Treatment of Rheumatoid Arthritis.
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DOI：
10.3389/fimmu.2021.790925
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发表时间：
2021
影响因子：
7.3
通讯作者：
Tang CH
中科院分区：
文献类型：
--
作者：
Achudhan D;Liu SC;Lin YY;Huang CC;Tsai CH;Ko CY;Chiang IP;Kuo YH;Tang CH
台湾传统药用蘑菇肉桂的提取物在细胞和临床前研究中显示出抗炎活性。然而，本文首次报道了从肉桂中分离出的三萜类化合物Antcin K能抑制类风湿关节炎(RA)疾病的主要致炎因子--类风湿滑膜成纤维细胞(RASF)的致炎细胞因子的产生。在我们对作用机制的分析中，抗菌素K抑制了三种细胞因子(肿瘤坏死因子α[肿瘤坏死因子-α]、白介素1β[IL-1β]和白介素8)在人RASF中的表达，这三种细胞因子对RA滑膜炎症至关重要。值得注意的是，与抗菌素K孵育的RASF减少了粘着斑激酶、磷脂酰肌醇3-激酶、蛋白激酶B和核因子-κB(NF-κB)信号通路的磷酸化，所有这些都促进了RA细胞因子的产生。腹腔注射抗菌素K(10 mg/kg或30 mg/kg)可减轻胶原性关节炎(CIA)小鼠足爪肿胀、软骨降解和骨质侵蚀，降低血清肿瘤坏死因子-α、IL-1β、IL-8水平；进一步实验，IL-6水平也有类似的降低。抗菌素K通过下调FAK、PI3K、AKT和NF-αB信号通路，抑制人RASF中肿瘤坏死因子-β、IL-1β和IL-8的表达。我们的数据支持使用抗菌素K治疗类风湿关节炎的临床研究。
Extracts from Taiwan’s traditional medicinal mushroom, Antrodia cinnamomea, exhibit anti-inflammatory activities in cellular and preclinical studies. However, this paper is the first to report that Antcin K, a triterpenoid isolated from A. cinnamomea, inhibits proinflammatory cytokine production in human rheumatoid synovial fibroblasts (RASFs), which are major players in rheumatoid arthritis (RA) disease. In our analysis of the mechanism of action, Antcin K inhibited the expression of three cytokines (tumor necrosis factor alpha [TNF-α], interleukin 1 beta [IL-1β] and IL-8) in human RASFs; cytokines that are crucial to RA synovial inflammation. Notably, incubation of RASFs with Antcin K reduced the phosphorylation of the focal adhesion kinase (FAK), phosphoinositide 3-kinase (PI3K), protein kinase B (AKT) and nuclear factor-κB (NF-κB) signaling cascades, all of which promote cytokine production in RA. Intraperitoneal injections of Antcin K (10 mg/kg or 30 mg/kg) attenuated paw swelling, cartilage degradation and bone erosion, and decreased serum levels of TNF-α, IL-1β, IL-8 in collagen-induced arthritis (CIA) mice; in further experiments, IL-6 levels were similarly reduced. The inhibitory effects of Antcin K upon TNF-α, IL-1β and IL-8 expression in human RASFs was achieved through the downregulation of the FAK, PI3K, AKT and NF-κB signaling cascades. Our data support clinical investigations using Antcin K in RA disease.