Anti-angiogenic effect of triptolide in rheumatoid arthritis by targeting angiogenic cascade

• Published in: PloS one 2013-10, Vol.8 (10), p.e77513
• Main Authors: Kong, Xiangying, Zhang, Yanqiong, Liu, Chunfang, Guo, Wei, Li, Xiangbin, Su, Xiaohui, Wan, Hongye, Sun, Yanqun, Lin, Na
• Format: Article
• Language: English
• Subjects: Adhesive joints; Angiogenesis; Angiogenesis Modulating Agents - metabolism; Animal tissues; Animals; Antiangiogenics; Arthritis; Arthritis, Experimental - drug therapy; Arthritis, Experimental - metabolism; Arthritis, Experimental - pathology; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - metabolism; Arthritis, Rheumatoid - pathology; Cancer; Cancer therapies; Capillaries; Cell adhesion; Cell Adhesion - drug effects; Cell Movement - drug effects; Cells, Cultured; Chemotaxis; Collagen; Collagen (type II); Collagen - metabolism; Disease; Diterpenes - pharmacology; Drug Combinations; Epoxy Compounds - pharmacology; Extracellular signal-regulated kinase; Government agencies; Human Umbilical Vein Endothelial Cells; Humans; Immune response; Immunization; Inflammation; Interleukin 1; Interleukin 17; JNK protein; Joint diseases; Laboratory animals; Laminin - metabolism; Male; MAP kinase; Mitogen-Activated Protein Kinases - metabolism; Neovascularization, Pathologic - drug therapy; Neovascularization, Pathologic - metabolism; Neovascularization, Pathologic - pathology; Phenanthrenes - pharmacology; Protein kinase; Proteoglycans - metabolism; Rats; Rheumatoid arthritis; Rodents; Synovial membrane; Synovial Membrane - drug effects; Synovial Membrane - metabolism; Synovial Membrane - pathology; Triptolide; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism; Vascular endothelial growth factor receptors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0077513

Rheumatoid arthritis (RA) is characterized by a pre-vascular seriously inflammatory phase, followed by a vascular phase with high increase in vessel growth. Since angiogenesis has been considered as an essential event in perpetuating inflammatory and immune responses, as well as supporting pannus growth and development of RA, inhibition of angiogenesis has been proposed as a novel therapeutic strategy for RA. Triptolide, a diterpenoid triepoxide from Tripterygium wilfordii Hook F, has been extensively used in treatment of RA patients. It also acts as a small molecule inhibitor of tumor angiogenesis in several cancer types. However, it is unclear whether triptolide possesses an anti-angiogenic effect in RA. To address this problem, we constructed collagen-induced arthritis (CIA) model using DA rats by the injection of bovine type II collagen. Then, CIA rats were treated with triptolide (11-45 µg/kg/day) starting on the day 1 after first immunization. The arthritis scores (P