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α-倒捻子素,一种天然的呫吨酮,诱导人类风湿关节炎成纤维样滑膜细胞 MH7A 细胞凋亡和 ROS 积累。

α-Mangostin, A Natural Xanthone, Induces Apoptosis and ROS Accumulation in Human Rheumatoid Fibroblast-Like Synoviocyte MH7A Cells.

机构信息

The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong. China.

Department of Pharmacology & Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, Guangdong. China.

出版信息

Curr Mol Med. 2017;17(5):375-380. doi: 10.2174/1566524018666171205123220.

Abstract

BACKGROUND

Rheumatoid arthritis (RA) is a complicated and heterogeneous chronic disease with the characteristic of progressive joint destruction, deformity and disability. It is associated with not only genetic but also environmental factors. Many studies suggest that RA-derived fibroblast-like synoviocyte (RA-FLS) is involved in the pathogenic process of RA. The apoptosis and proliferation of RA-FLS is of great importance in the development and progression in RA. Nowadays, more and more traditional Chinese medicine (TCM) or natural products are studied in the treatment of RA.

OBJECTIVE

To investigate the effects of several natural products and the apoptosisinduced effect of α-mangostin and its underlying mechanisms in RA-FLS MH7A cells.

METHODS

The effects of natural products on MH7A cells were detected by MTT assay. Annexin V-FITC/PI double labeling and DAPI staining were adopted to observe the apoptosis induced by α-mangostin. The apoptosis related proteins were measured with western blotting analysis. ROS accumulation was determined by DHE staining.

RESULTS

Xantones, including Garcinone C, α-mangostin and γ-mangostin, significantly inhibited the MH7A cell viability. And α-mangostin induces apoptosis in MH7A cells. Further study showed that α-mangostin increased the ratio of Bax/Bcl-2 and increased the ROS generation in MH7A cells.

CONCLUSION

α-Mangostin induces the apoptosis of MH7A cells through increasing ROS accumulation and the ratio of Bax/Bcl-2, suggesting that α-mangostin should be benefit to the therapy of RA.

摘要

背景

类风湿关节炎(RA)是一种复杂且异质性的慢性疾病,具有进行性关节破坏、畸形和残疾的特征。它不仅与遗传因素有关,还与环境因素有关。许多研究表明,类风湿关节炎衍生的成纤维样滑膜细胞(RA-FLS)参与了 RA 的发病过程。RA-FLS 的凋亡和增殖对 RA 的发展和进展至关重要。如今,越来越多的中药(TCM)或天然产物被用于治疗 RA。

目的

探讨几种天然产物对 MH7A 细胞的影响,以及 α-倒捻子素诱导 RA-FLS MH7A 细胞凋亡的作用及其机制。

方法

采用 MTT 法检测天然产物对 MH7A 细胞的作用。采用 Annexin V-FITC/PI 双染和 DAPI 染色观察 α-倒捻子素诱导的凋亡。采用 Western blot 分析检测凋亡相关蛋白。采用 DHE 染色检测 ROS 积累。

结果

呫吨酮类化合物,包括 Garcinone C、α-倒捻子素和 γ-倒捻子素,显著抑制 MH7A 细胞活力。α-倒捻子素诱导 MH7A 细胞凋亡。进一步研究表明,α-倒捻子素增加了 Bax/Bcl-2 的比值,并增加了 MH7A 细胞中的 ROS 生成。

结论

α-倒捻子素通过增加 ROS 积累和 Bax/Bcl-2 的比值诱导 MH7A 细胞凋亡,提示α-倒捻子素可能有益于 RA 的治疗。

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