1. Shikonin induces programmed death of fibroblast synovial cells in rheumatoid arthritis by inhibiting energy pathways.
- Author
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Li J, Pang J, Liu Z, Ge X, Zhen Y, Jiang CC, Liu Y, Huo Q, Sun Y, and Liu H
- Subjects
- Adenosine Triphosphate metabolism, Animals, Arthritis, Rheumatoid metabolism, Autophagy drug effects, Cell Line, Disease Models, Animal, Energy Metabolism drug effects, Humans, Interleukins metabolism, Male, Phosphatidylinositol 3-Kinase metabolism, Proto-Oncogene Proteins c-akt metabolism, Rats, Rats, Sprague-Dawley, Reactive Oxygen Species metabolism, Signal Transduction drug effects, Synoviocytes metabolism, TOR Serine-Threonine Kinases metabolism, Anti-Inflammatory Agents pharmacology, Apoptosis drug effects, Arthritis, Rheumatoid drug therapy, Naphthoquinones pharmacology, Synoviocytes drug effects
- Abstract
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-α, IL-6, IL-8, IL-10, IL-17A, and IL-1β while showing less toxicity to the liver and kidney., (© 2021. The Author(s).)
- Published
- 2021
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