2. Academic Validation
  3. Kurarinone Attenuates Collagen-Induced Arthritis in Mice by Inhibiting Th1/Th17 Cell Responses and Oxidative Stress

Kurarinone Attenuates Collagen-Induced Arthritis in Mice by Inhibiting Th1/Th17 Cell Responses and Oxidative Stress

  • Int J Mol Sci. 2021 Apr 13;22(8):4002. doi: 10.3390/ijms22084002.
Kuo-Tung Tang 1 2 3,  Chi-Chien Lin 1 4 5 6 7,  Shih-Chao Lin 8,  Jou-Hsuan Wang 9,  Sen-Wei Tsai 9 10
Affiliations

Affiliations

  • 1 Program in Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan.
  • 2 Faculty of Medicine, National Yang-Ming University, Taipei 112, Taiwan.
  • 3 Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung 407, Taiwan.
  • 4 Institute of Biomedical Science, The iEGG and Animal Biotechnology Center, National Chung-Hsing University, Taichung 402, Taiwan.
  • 5 Department of Medical Research, China Medical University Hospital, Taichung 404, Taiwan.
  • 6 Department of Medical Research, Taichung Veterans General Hospital, Taichung 407, Taiwan.
  • 7 Department of Pharmacology, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
  • 8 Bachelor Degree Program in Marine Biotechnology, College of Life Sciences, National Taiwan Ocean University, Keelung 202, Taiwan.
  • 9 Department of Physical Medicine and Rehabilitation, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung 427, Taiwan.
  • 10 School of Medicine, Tzu Chi University, Hualien 970, Taiwan.
PMID: 33924467 DOI: 10.3390/ijms22084002
Abstract

Kurarinone is a flavanone, extracted from Sophora flavescens Aiton, with multiple biological effects. Here, we determine the therapeutic potential of kurarinone and elucidate the interplay between kurarinone and the autoimmune disease rheumatoid arthritis (RA). Arthritis was recapitulated by induction of bovine collagen II (CII) in DBA/1 mice as a collagen-induced arthritis (CIA) model. After the establishment of the CIA, kurarinone was given orally from day 21 to 42 (100 mg/kg/day) followed by determination of the severity based on a symptom scoring scale and with histopathology. Levels of cytokines, anti-CII Antibodies, and the proliferation and lineages of T cells from the draining lymph nodes were measured using ELISA and flow cytometry, respectively. The expressional changes, including STAT1, STAT3, Nrf2, KEAP-1, and heme oxygenase-1 (HO-1) changes in the paw tissues, were evaluated by Western blot assay. Oxidative stress featured with malondiadehyde (MDA) and hydrogen peroxide (H2O2) activities in paw tissues were also evaluated. Results showed that kurarinone treatment reduced arthritis severity of CIA mice, as well as their levels of proinflammatory cytokines, TNF-α, IL-6, IFN-γ, and IL-17A, in the serum and paw tissues. T cell proliferation was also reduced by kurarinone even under the stimulation of CII and anti-CD3 antibody. In addition, kurarinone reduced STAT1 and STAT3 phosphorylation and the proportions of Th1 and Th17 cells in lymph nodes. Moreover, kurarinone suppressed the production of MDA and H2O2. All while promoting enzymatic activities of key antioxidant Enzymes, SOD and GSH-Px. In the paw tissues, upregulation of Nrf-2 and HO-1, and downregulation of KEAP-1 were observed. Overall, kurarinone showed an anti-inflammatory effect by inhibiting Th1 and Th17 cell differentiation and an antioxidant effect exerted in part through activating the Nrf-2/KEAP-1 pathway. These beneficial effects in CIA mice contributed to the amelioration of their arthritis, indicating that kurarinone might be an adjunct treatment option for rheumatoid arthritis.

Keywords

STAT1; STAT3; Th1; Th17; arthritis; kurarinone; oxidative stress.

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