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09 September 2019 : Laboratory Research  

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

Yun-Xiang Cao1ABCDEFG*, Dan Huang1ABCDEF, Jian Liu1ABCDEF, Rui-Kai Zong1BCDF, Lei Wan1BCDF, Chuan-Bing Huang1BCDF, Wan-Dong Zhang1BCDF, Yuan Wang1BCF

DOI: 10.12659/MSM.916317

Med Sci Monit 2019; 25:6767-6774

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 AND 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.

Keywords: Cardiomyopathies, Hereditary Autoinflammatory Diseases, Myocardium, Toll-Like Receptor 4, Arthritis, Experimental, Capsules, Cytokines, Drugs, Chinese Herbal, Gene Expression Regulation, Inflammation Mediators, Mitogen-Activated Protein Kinases, Phosphorylation

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750