Department of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, China.
Am J Chin Med. 2013;41(3):615-28. doi: 10.1142/S0192415X13500432.
Celastrol is one of the principal active ingredients of Tripterygium wilfordii Hook.f., a toxic Chinese medical herb traditionally prescribed for controlling pain and inhibiting inflammation in various chronic inflammatory diseases, including rheumatoid arthritis (RA). Resistance to apoptosis of fibroblast-like synoviocytes is considered a major characteristic of RA. In this study, we test celastrol's cytotoxic effect and potential mechanisms in human rheumatoid synovial fibroblasts (RA-FLS). In the cytotoxic assay, we found that celastrol dose-dependently decreased RA-FLS viability and increased LDH release. The apoptotic nuclear morphology was observed after celastrol treatment as determined by DAPI fluorescence staining. Flow cytometry analysis with PI and Annexin V revealed that celastrol induced RA-FLS cell cycle arrest in the G2/M phase and apoptosis. Furthermore, celastrol dramatically increased expression of Bax/Bcl-2, proteolytic cleavage of Caspase-3, -9, PARP, and decreased expression of FasR. In addition, celastrol treatment resulted in DNA damage. Collectively, we concluded that celastrol inhibits RA-FLS proliferation by inducing DNA damage, cell cycle arrest, and apoptosis in vitro, which might provide data for its application in RA treatment.
雷公藤红素是卫矛科植物雷公藤（Tripterygium wilfordii Hook.f.）的主要活性成分之一，雷公藤是一种有毒的中药，传统上用于治疗各种慢性炎症性疾病，包括类风湿关节炎（RA）的疼痛和炎症抑制。成纤维样滑膜细胞（fibroblast-like synoviocytes，FLS）抵抗细胞凋亡被认为是 RA 的主要特征之一。在这项研究中，我们测试了雷公藤红素对人类风湿滑膜成纤维细胞（rheumatoid synovial fibroblasts，RA-FLS）的细胞毒性作用及其潜在机制。在细胞毒性测定中，我们发现雷公藤红素剂量依赖性地降低 RA-FLS 活力并增加 LDH 释放。DAPI 荧光染色后观察到雷公藤红素处理后的凋亡核形态。PI 和 Annexin V 的流式细胞术分析显示，雷公藤红素诱导 RA-FLS 细胞周期阻滞在 G2/M 期并诱导细胞凋亡。此外，雷公藤红素显著增加了 Bax/Bcl-2 的表达，Caspase-3、-9、PARP 的蛋白水解切割，以及 FasR 的表达降低。此外，雷公藤红素处理导致 DNA 损伤。总之，我们得出结论，雷公藤红素通过在体外诱导 DNA 损伤、细胞周期阻滞和凋亡来抑制 RA-FLS 的增殖，这可能为其在 RA 治疗中的应用提供数据。
