连翘脂苷 A 在体外类风湿关节炎模型中具有抗迁移和抗炎作用。
Forsythiaside A exhibits anti-migration and anti-inflammation effects in rheumatoid arthritis in vitro model.
机构信息
Department of Rheumatology, Changzhou Hospital of Traditional Chinese Medicine, Affiliated to Nanjing University of Traditional Chinese Medicine, Changzhou, Jiangsu Province, China.
出版信息
Int J Rheum Dis. 2024 Jan;27(1):e14976. doi: 10.1111/1756-185X.14976. Epub 2023 Nov 24.
BACKGROUND
Rheumatoid arthritis (RA) is a kind of systemic autoimmune disease, and the joint inflammation and cartilage destruction are the major features. Some traditional Chinese medicine have been discovered to exhibit regulatory roles in the treatment of RA. Forsythiaside A (FA) as an active ingredient isolated from forsythia suspensa has been discovered to participate into the regulation of some diseases through improving inflammation. However, the regulatory effects of FA on the progression of RA keep indistinct.
METHODS
IL-1β treatment (10 ng/mL) in MH7A cells was built to mimic RA in vitro (cell) model. The cell viability was examined through CCK-8 assay. The cell proliferation was detected through Edu assay. The levels of TNF-α, IL-6, and IL-8 were evaluated through ELISA. The protein expressions were measured through western blot. The cell apoptosis was assessed through flow cytometry. The cell migration and invasion abilities were tested through Transwell assay.
RESULTS
In this study, it was revealed that the cell proliferation was strengthened after IL-1β treatment (p < .001), but this effect was reversed after FA treatment in a dose-increasing manner (p < .05). Furthermore, FA suppressed inflammation in IL-1β-triggered MH7A cells through attenuating the levels of TNF-α, IL-6, and IL-8 (p < .05). The cell apoptosis was lessened after IL-1β treatment (p < .001), but this effect was rescued after FA treatment (p < .05). Besides, the cell migration and invasion abilities were both increased after IL-1β treatment (p < .001), but these changes were offset after FA treatment (p < .05). Eventually, FA retarded the JAK/STAT pathway through reducing p-JAK/JAK and p-STAT/STAT levels (p < .01).
CONCLUSION
Our study manifested that FA exhibited anti-migration and anti-inflammation effects in RA in vitro model (IL-1β-triggered MH7A cells) through regulating the JAK/STAT pathway. This work hinted that FA can be an effective drug for RA treatment.
背景
类风湿关节炎（RA）是一种系统性自身免疫性疾病，其主要特征为关节炎症和软骨破坏。一些中药已被发现具有调节 RA 治疗的作用。连翘酯苷 A（FA）作为连翘中的一种活性成分，已被发现通过改善炎症参与一些疾病的调节。然而，FA 对 RA 进展的调节作用仍不明确。
方法
在 MH7A 细胞中建立 IL-1β（10ng/mL）处理以模拟 RA 的体外（细胞）模型。通过 CCK-8 检测细胞活力。通过 Edu 检测检测细胞增殖。通过 ELISA 评估 TNF-α、IL-6 和 IL-8 的水平。通过 Western blot 测量蛋白表达。通过流式细胞术评估细胞凋亡。通过 Transwell 检测评估细胞迁移和侵袭能力。
结果
在这项研究中，发现 IL-1β 处理后细胞增殖增强（p<0.001），但 FA 处理呈剂量依赖性地逆转了这种作用（p<0.05）。此外，FA 通过减弱 TNF-α、IL-6 和 IL-8 的水平抑制了 IL-1β 触发的 MH7A 细胞中的炎症（p<0.05）。IL-1β 处理后细胞凋亡减少（p<0.001），但 FA 处理后这种作用得到挽救（p<0.05）。此外，IL-1β 处理后细胞迁移和侵袭能力均增加（p<0.001），但 FA 处理后这些变化得到抵消（p<0.05）。最终，FA 通过降低 p-JAK/JAK 和 p-STAT/STAT 水平抑制了 JAK/STAT 通路（p<0.01）。
结论
我们的研究表明，FA 通过调节 JAK/STAT 通路在 RA 的体外模型（IL-1β 触发的 MH7A 细胞）中表现出抗迁移和抗炎作用。这项工作暗示 FA 可以成为 RA 治疗的有效药物。
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