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伞形花内酯通过MAPK/NF-κB信号通路对佐剂诱导的大鼠关节炎的影响

Effect of umbelliferone on adjuvant-induced arthritis in rats by MAPK/NF-κB pathway.

作者信息

Ouyang Liu, Dan Yang, Shao Zengwu, Yang Shuhua, Yang Cao, Liu Guohui, Zhou Wu, Duan Deyu

机构信息

Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People's Republic of China,

出版信息

Drug Des Devel Ther. 2019 Apr 11;13:1163-1170. doi: 10.2147/DDDT.S190155. eCollection 2019.

Abstract

PURPOSE

Umbelliferone (Umb), a member of coumarin family, is found in many plants and is a promising molecule with potential anti-inflammatory, anti-oxidative, and anti-tumor activities. However, the effect of Umb on arthritis remains unclear.

METHODS

A rat model with Freund's complete adjuvant (FCA)-induced arthritis was developed and used to test the efficacy of Umb on arthritis rats. Rats were given an intragastric injection of Umb (20 and 40 mg/kg) once daily from days 21 to 28 after the administration of FCA. Hind paw volume was assessed using a volume meter. The pro-inflammatory cytokine levels and prostaglandin E2 (PEG2) level in serum and synovial fluid were detected by ELISA. HE staining was used to determine representative histological changes in joint tissues, and Western blot analysis was employed to study the effects of Umb on MAPK/NF-κB signaling pathway.

RESULTS

Our results showed that Umb suppressed the release of IL-6, IL-1β, tumor necrosis factor-alpha, and PEG2. In addition, Umb could also dramatically ameliorate the pathological changes observed in rat joints. Based on the results of Western blot, we also observed that Umb could strikingly suppress the expression of MAPK/NF-κB pathway molecules.

CONCLUSION

These results proved that treatment with Umb is very effective for arthritis and inhibiting the MAPK/NF-κB signaling pathway may be a potential therapeutic target for treatment of arthritis.

摘要

目的

伞形花内酯(Umb)是香豆素家族的一员,存在于许多植物中,是一种具有潜在抗炎、抗氧化和抗肿瘤活性的有前景的分子。然而,Umb对关节炎的影响仍不清楚。

方法

建立弗氏完全佐剂(FCA)诱导的大鼠关节炎模型,用于测试Umb对关节炎大鼠的疗效。在给予FCA后第21天至28天,大鼠每天一次灌胃给予Umb(20和40mg/kg)。使用体积计评估后足体积。通过ELISA检测血清和滑液中促炎细胞因子水平和前列腺素E2(PEG2)水平。采用HE染色确定关节组织的代表性组织学变化,并采用蛋白质印迹分析研究Umb对MAPK/NF-κB信号通路的影响。

结果

我们的结果表明,Umb抑制了IL-6、IL-1β、肿瘤坏死因子-α和PEG2的释放。此外,Umb还可以显著改善大鼠关节中观察到的病理变化。基于蛋白质印迹结果,我们还观察到Umb可以显著抑制MAPK/NF-κB通路分子的表达。

结论

这些结果证明,Umb治疗对关节炎非常有效,抑制MAPK/NF-κB信号通路可能是治疗关节炎的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbff/6469479/420d1b5b6217/dddt-13-1163Fig1.jpg

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