The immunosuppressive effects and mechanisms of loureirin B on collagen-induced arthritis in rats

Abstract

IntroductionRheumatoid arthritis (RA) is a common disease mainly affecting joints of the hands and wrists. The discovery of autoantibodies in the serum of patients revealed that RA belonged to the autoimmune diseases and laid a theoretical basis for its immunosuppressive therapy. The pathogenesis of autoimmune diseases mainly involves abnormal activation and proliferation of effector memory T cells, which is closely related to the elevated expression of Kv1.3, a voltage-gated potassium (Kv) channel on the effector memory T cell membrane. Drugs blocking the Kv1.3 channel showed a strong protective effect in RA model animals, suggesting that Kv1.3 is a target for the discovery of specific RA immunosuppressive drugs.MethodsIn the present study, we synthesized LrB and studied the effects of LrB on collagen- induced arthritis (CIA) in rats. The clinical score, paw volume and joint morphology of CIA model rats were compared. The percentage of CD3+, CD4+ and CD8+ T cells in rat peripheral blood mononuclear and spleen were analyzed with flow cytometry. The concentrations of inflammatory cytokines interleukin (IL)-1b, IL-2, IL-4, IL-6, IL-10 and IL-17 in the serum of CIA rats were analyzed with enzyme-linked immunosorbent assay. The IL-1b and IL-6 expression in joints and the Kv1.3 expression in peripheral blood mononuclear cells (PBMCs) were quantified by qPCR. To further study the mechanisms of immunosuppressive effects of LrB, western blot and immunofluorescence were utilized to study the expression of Kv1.3 and Nuclear Factor of Activated T Cells 1 (NFAT1) in two cell models - Jurkat T cell line and extracted PBMCs.ResultsLrB effectively reduced the clinical score and relieved joint swelling. LrB could also decrease the percentage of CD4+ T cells, while increase the percentage of CD8+ T cells in peripheral blood mononuclear and spleen of rats with CIA. The concentrations of inflammatory cytokines interleukin (IL)-1b, IL-2, IL-6, IL-10 and IL-17 in the serum of CIA rats were significantly reduced by LrB. The results of qPCR showed that Kv1.3 mRNA in the PBMCs of CIA rats was significantly higher than that of the control and significantly decreased in the LrB treatment groups. In addition, we confirmed in cell models that LrB significantly decreased Kv1.3 protein on the cell membrane and inhibited the activation of Nuclear Factor of Activated T Cells 1 (NFAT1) with immune stimulus.ConclusionIn summary, this study revealed that LrB could block NFAT1 activation and reduce Kv1.3 expression in activated T cells, thus inhibiting the proliferation of lymphocytes and the release of inflammatory cytokines, thereby effectively weakening the autoimmune responses in CIA rats. The effects of immunosuppression due to LrB revealed its potential medicinal value in the treatment of RA.

Plant‐derived flavonoids are a potential source of drugs for the treatment of liver fibrosis

“…Loureirin B is a flavonoid extracted from Dracaena cochinchinensis, and has a variety of pharmacological effects including promoting insulin secretion, preventing osteoporosis, and treating rheumatoid arthritis (Fang et al, 2022;Yuhao Liu et al, 2019;Zou et al, 2023). It has been reported that loureirin B can inhibit TGF-β1-induced myofibroblast differentiation in cardiac fibroblasts, thereby improving cardiac fibrosis (Cheng et al, 2022).…”

Identification of chalcone analogues as anti-inflammatory agents through the regulation of NF-κB and JNK activation

“…1, loureirin A, loureirin B, and cochinchinenin A, belonging to dihydrochalcones, are important bioactive natural products (BNPs) found in Resina Draconis . 15 Recently, numerous studies have reported that both naturally occurring and synthetic chalcones and dihydrochalcones as anti-inflammatory agents are involved in the inhibition of cytokines and inflammatory mediator production in inflammatory disorders. 13,16–20 However, limited studies are reported on evaluating the anti-inflammatory activity of chalcones and dihydrochalcones or their structure–activity relationships (SARs).…”