Open Access
Frontiers in Pharmacology, volume 11
Therapeutic Effects of Tryptanthrin and Tryptanthrin-6-Oxime in Models of Rheumatoid Arthritis
Kirpotina Liliya N.
1
,
Schepetkin Igor A.
1
,
Hammaker Deepa
2
,
Kuhs Amanda
2
,
Khlebnikov Andrei I.
3, 4
,
Quinn Mark T.
1
1
Department of Microbiology and Immunology, Montana State University, United States
|
2
Division of Rheumatology, Allergy, and Immunology, School of Medicine, University of California, San Diego, United States
|
Publication type: Journal Article
Publication date: 2020-07-24
Journal:
Frontiers in Pharmacology
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor: 5.6
ISSN: 16639812
Pharmacology
Pharmacology (medical)
Abstract
Rheumatoid arthritis (RA) is a chronic destructive autoimmune disorder characterized by joint and bone destruction that is mediated in part by proteases and cytokines produced by synovial macrophages and FLS. Although current biological therapeutic strategies for RA have been effective in many cases, new classes of therapeutics are needed. Here, we investigated the anti-inflammatory effects of plant-derived alkaloid tryptanthrin (Trp) and its synthetic derivative tryptanthrin-6-oxime (Trp-Ox). Both Trp and Trp-Ox inhibited matrix metalloproteinase (MMP)-3 expression in interleukin (IL)-1β-stimulated primary human fibroblast-like synoviocytes (FLS), IL-1β-stimulated secretion of MMP-1/3 in synovial SW-982 cells, and production of IL-6 in human umbilical vein endothelial cells (HUVECs), SW-982 cells, and monocytic THP-1 cells, although Trp-Ox was much more effective. Evaluation of the therapeutic potential of Trp and Trp-Ox in murine arthritis models showed that both compounds significantly attenuated development of collagen-induced arthritis (CIA) and collagen-antibody-induced arthritis (CAIA), with Trp-Ox again being the most effective. Collagen II (CII)-specific antibody levels were reduced in Trp- and Trp-Ox-treated in CIA mice. Trp and Trp-Ox suppressed proinflammatory cytokine production by lymph node cells, with Trp-Ox being more effective in inhibiting IL-17A, granulocyte-macrophage colony-stimulating factor (GM-CSF), and receptor activator of nuclear factor-κB ligand (RANKL). While both Trp and Trp-Ox were both effective in inhibiting RA, Trp-Ox was the most effective, which is likely due to its ability to inhibit c-Jun N-terminal kinase (JNK), which is not a target of Trp. Overall, Trp-Ox may represent a potential new direction for pursuit of novel treatments for RA.
Citations by journals
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International Journal of Molecular Sciences
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International Journal of Molecular Sciences
2 publications, 8.33%
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1 publication, 4.17%
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Biochemistry and Biophysics Reports
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European Journal of Medicinal Chemistry
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Heliyon
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Journal of Agricultural and Food Chemistry
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1 publication, 4.17%
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1 publication, 4.17%
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Pharmaceuticals
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1 publication, 4.17%
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Mini-Reviews in Medicinal Chemistry
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1 publication, 4.17%
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1 publication, 4.17%
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1 publication, 4.17%
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1 publication, 4.17%
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Citations by publishers
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8
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Multidisciplinary Digital Publishing Institute (MDPI)
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8 publications, 33.33%
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Elsevier
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Elsevier
4 publications, 16.67%
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Springer Nature
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Springer Nature
3 publications, 12.5%
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Wiley
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Wiley
2 publications, 8.33%
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Frontiers Media S.A.
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Frontiers Media S.A.
1 publication, 4.17%
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American Chemical Society (ACS)
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American Chemical Society (ACS)
1 publication, 4.17%
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Royal Society of Chemistry (RSC)
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Royal Society of Chemistry (RSC)
1 publication, 4.17%
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Oxford University Press
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Oxford University Press
1 publication, 4.17%
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Bentham Science
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Bentham Science
1 publication, 4.17%
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Taylor & Francis
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Taylor & Francis
1 publication, 4.17%
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- We do not take into account publications that without a DOI.
- Statistics recalculated only for publications connected to researchers, organizations and labs registered on the platform.
- Statistics recalculated weekly.
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Kirpotina L. N. et al. Therapeutic Effects of Tryptanthrin and Tryptanthrin-6-Oxime in Models of Rheumatoid Arthritis // Frontiers in Pharmacology. 2020. Vol. 11.
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Kirpotina L. N., Schepetkin I. A., Hammaker D., Kuhs A., Khlebnikov A. I., Quinn M. T. Therapeutic Effects of Tryptanthrin and Tryptanthrin-6-Oxime in Models of Rheumatoid Arthritis // Frontiers in Pharmacology. 2020. Vol. 11.
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TY - JOUR
DO - 10.3389/fphar.2020.01145
UR - https://doi.org/10.3389%2Ffphar.2020.01145
TI - Therapeutic Effects of Tryptanthrin and Tryptanthrin-6-Oxime in Models of Rheumatoid Arthritis
T2 - Frontiers in Pharmacology
AU - Kirpotina, Liliya N.
AU - Schepetkin, Igor A.
AU - Hammaker, Deepa
AU - Kuhs, Amanda
AU - Khlebnikov, Andrei I.
AU - Quinn, Mark T.
PY - 2020
DA - 2020/07/24 00:00:00
PB - Frontiers Media S.A.
VL - 11
SN - 1663-9812
ER -
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@article{2020_Kirpotina,
author = {Liliya N. Kirpotina and Igor A. Schepetkin and Deepa Hammaker and Amanda Kuhs and Andrei I. Khlebnikov and Mark T. Quinn},
title = {Therapeutic Effects of Tryptanthrin and Tryptanthrin-6-Oxime in Models of Rheumatoid Arthritis},
journal = {Frontiers in Pharmacology},
year = {2020},
volume = {11},
publisher = {Frontiers Media S.A.},
month = {jul},
url = {https://doi.org/10.3389%2Ffphar.2020.01145},
doi = {10.3389/fphar.2020.01145}
}