ReferenceID 3089
Therapeutic Effects of Tryptanthrin and Tryptanthrin-6-Oxime in Models of Rheumatoid Arthritis
Front Pharmacol
Rheumatoid arthritis (RA) is a chronic autoimmune disease involving joint and bone damage that is mediated in part by proteases and cytokines produced by synovial macrophages and fibroblast-like synoviocytes (FLS). Altho
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- Reference Id
- 3089
- Evidence Id
- 19679
- Core Evidence Id
- 19679
- Source Reference Id
- 6177
- Herb2 Reference Id
- HBREF006974
- Subject Paper Key
- HBIN047278_32792961
- Pubmed Id
- 32792961
- Doi
- 10.3389/fphar.2020.01145
- Paper Title
- Therapeutic Effects of Tryptanthrin and Tryptanthrin-6-Oxime in Models of Rheumatoid Arthritis
- Paper Abstract
- Rheumatoid arthritis (RA) is a chronic autoimmune disease involving joint and bone damage that is mediated in part by proteases and cytokines produced by synovial macrophages and fibroblast-like synoviocytes (FLS). Although current biological therapeutic strategies for RA have been effective in many cases, new classes of therapeutics are needed. We investigated anti-inflammatory properties of the natural alkaloid tryptanthrin (TRYP) and its synthetic derivative tryptanthrin-6-oxime (TRYP-Ox). Both TRYP and TRYP-Ox inhibited matrix metalloproteinase (MMP)-3 gene expression in interleukin (IL)-1beta-stimulated primary human FLS, as well as IL-1beta-induced secretion of MMP-1/3 by FLS and synovial SW982 cells and IL-6 by FLS, SW982 cells, human umbilical vein endothelial cells (HUVECs), and monocytic THP-1 cells, although TRYP-Ox was generally more effective and had no cytotoxicity in vitro. Evaluation of the therapeutic potential of TRYP and TRYP-Ox in vivo in murine arthritis models showed that both compounds significantly attenuated the development of collagen-induced arthritis (CIA) and collagen-antibody-induced arthritis (CAIA), with comparable efficacy. Collagen II (CII)-specific antibody levels were similarly reduced in TRYP- and TRYP-Ox-treated CIA mice. TRYP and TRYP-Ox also suppressed proinflammatory cytokine production by lymph node cells from CIA mice, with TRYP-Ox being more effective in inhibiting IL-17A, granulocyte-macrophage colony-stimulating factor (GM-CSF), and receptor activator of nuclear factor-kappaB ligand (RANKL). Thus, even though TRYP-Ox generally had a better in vitro profile, possibly due to its ability to inhibit c-Jun N-terminal kinase (JNK), both TRYP and TRYP-Ox were equally effective in inhibiting the clinical symptoms and damage associated with RA. Overall, TRYP and/or TRYP-Ox may represent potential new directions for the pursuit of novel treatments for RA.
- Journal
- Front Pharmacol
- Publish Year
- 2020
- Experiment Subject
- mouse; human; human umbilical vein endothelial cells; huvecs; interleukin (il)-1beta-stimulated primary human fls; monocytic thp-1 cells; sw982 cells; synovial sw982 cells
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Joint And Bone Damage; Chronic Autoimmune Disease; Rheumatoid Arthritis; Arthritis; Collagen-induced Arthritis; Collagen-antibody-induced Arthritis
- Paper Title Cn
- Paper Title En
- Therapeutic Effects of Tryptanthrin and Tryptanthrin-6-Oxime in Models of Rheumatoid Arthritis
- Bilingual Status
- semi_complete