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.