A Novel Chinese Medicine, Xinfeng Capsule, Modulates Proinflammatory Cytokines via Regulating the Toll-Like Receptor 4 (TLR4)/Mitogen-Activated Protein Kinase (MAPK)/Nuclear Kappa B (NF-κB) Signaling Pathway in an Adjuvant Arthritis Rat Model

Abstract

Background

Rheumatoid arthritis (RA) is a chronic autoimmune disease targeting joints. This research aimed to explore the effects of Xinfeng capsules (XFC) on cardiac injury in adjuvant arthritis (AA) model rats and assessed the associated mechanism.

Material/Methods

An adjuvant arthritis (AA) rat model was established by intracutaneously injection with Freund’s complete adjuvant (FCA). Model rats were divided into 4 groups: an AA model group, an astragalus polysaccharides (APS) group, a methotrexate (MTX) group, and an XFC and triptolide (TPT) group. Hematoxylin-eosin (HE) staining was used to observe histopathologic changes. TUNEL assay was utilized to evaluate the apoptosis of cardiomyocytes. ELISA was utilized to evaluate levels of tumor necrosis factor α (TNF-α), interleukin 17 (IL-17), and interleukin 6 (IL-6) in myocardial tissues. Quantitative RT-PCR (qRT-PCR) was used to detect microRNA-21 (miRNA21) levels. Mitogen-activated protein kinase (MAPK)/p38, Toll-like receptor 4 (TLR4), and nuclear kappa B (NF-κB)/p65 levels were evaluated using Western blot.

Results

XFC significantly improved proinflammatory response compared to the AA model group ( p<0.05). XFC treatment significantly decreased the number of cells staining TUNEL-positive compared with the model group ( p<0.05). XFC treatment significantly reduced TNF-α, IL-17, and IL-6 levels in myocardial tissues compared to the model group ( p<0.05). Levels of miRNA21 were significantly lower in the XFC group compared to the AA model group ( p<0.05). TLR4, MAPK/p38, and NF-κB/p65 expression levels were significantly lower in the XFC group than in the model group ( p<0.05).

Conclusions

Xinfeng capsule, a traditional Chinese medicine preparation, protects against cardiac injury in AA rats by modulating proinflammatory cytokines expression via the TLR4/MAPK/NF-κB signaling pathway.