Shikonin induces programmed death of fibroblast synovial cells in rheumatoid arthritis by inhibiting energy pathways

被引:25
|
作者
Li, Jiahui [1 ]
Pang, Jinglong [1 ]
Liu, Zhe [2 ]
Ge, XianMing [1 ]
Zhen, Yanan [1 ]
Jiang, Chen Chen [3 ,4 ]
Liu, Yaming [1 ]
Huo, Qiang [1 ]
Sun, Yiming [2 ]
Liu, Hao [1 ]
机构
[1] Bengbu Med Coll, Sch Pharm, Donghai Rd, Bengbu 233030, Anhui, Peoples R China
[2] Bengbu Med Coll, Affiliated Hosp 1, Zhihuai Rd, Bengbu 233000, Anhui, Peoples R China
[3] Univ Newcastle, Sch Biomed Sci & Pharm, Canc Neurobiol Grp, Callaghan, NSW 2308, Australia
[4] Hunter Med Res Inst, New Lambton, NSW 2305, Australia
基金
中国国家自然科学基金;
关键词
APOPTOSIS; HYPOXIA; EXPRESSION; ISOMERASE; GROWTH; LINES;
D O I
10.1038/s41598-021-97713-6
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Shikonin is the main component of the traditional Chinese medicine comfrey, which can inhibit the activity of PKM2 by regulating glycolysis and ATP production. Rheumatoid arthritis synovial cells (RA-FLSs) have been reported to increase glycolytic activity and have other similar hallmarks of metabolic activity. In this study, we investigated the effects of shikonin on glycolysis, mitochondrial function, and cell death in RA-FLSs. The results showed that shikonin induced apoptosis and autophagy in RA-FLSs by activating the production of reactive oxygen species (ROS) and inhibiting intracellular ATP levels, glycolysis-related proteins, and the PI3K-AKT-mTOR signaling pathway. Shikonin can significantly reduce the expression of apoptosis-related proteins, paw swelling in rat arthritic tissues, and the levels of inflammatory factors in peripheral blood, such as TNF-alpha, IL-6, IL-8, IL-10, IL-17A, and IL-1 beta while showing less toxicity to the liver and kidney.
引用
收藏
页数:13
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