Baicalin Ameliorates Collagen-Induced Arthritis Through the Suppression of Janus Kinase 1 (JAK1)/Signal Transducer and Activator of Transcription 3 (STAT3) Signaling in Mice
Chunxiao Wang, Yong Song, Xin Wang, Ruijun Mao, Lijun Song
(Department of Rheumatology, Qilu Hospital of Shandong University, Ji’nan, Shandong, China (mainland))
Med Sci Monit 2018; 24:9213-9222
Rheumatoid arthritis is an autoimmune disease that causes chronic joint inflammation and there is no cure. Baicalin, as an ingredient in the roots of Scutellaria baicalensis, is supposed to possess an anti-inflammatory effect. However, the protective effect of baicalin on collagen-induced arthritis requires further investigation.
MATERIAL AND METHODS: A model of rheumatoid arthritis was established in 20 mice (8- to 10-weeks old). The mice were randomly divided into 2 groups after modeling and then injected with saline or baicalin, respectively. The synovial fluids and tissues were collected, and the pressure pain threshold and clinical arthritis score were measured. The levels of tumor necrosis factor (TNF)-α, interlukin-1β (IL-1β), IL-6, matrix metalloproteinases (MMP)-2, MMP-9, nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and their downstream inflammatory mediators Janus kinase 1 (JAK1)/signal transducer and activator of transcription 3 (STAT3), extracellular signal-regulated kinases 1/2 (ERK1/2), p38, Jun N-terminal kinases (JNK) activation were detected using enzyme-linked immunosorbent assay (ELISA), and western blotting analyses. The mononuclear cells apoptosis ratio was calculated by flowcytometry analyses.
RESULTS: Baicalin significantly reduced disease activities in a rheumatoid arthritis mouse model, which were reflected by pressure pain thresholds and clinical arthritis scores. Relevant proinflammatory cytokines such as TNF-α, IL-1β, IL-6, gelatinases (MMP-2, MMP-9) and inducible enzymes (iNOS, COX-2) were generally suppressed. Moreover, baicalin treatment induced cells apoptosis in synovial fluid monocytes and markedly down regulated JAK1/STAT3 but not mitogen-activated protein kinases (MAPKs) expressions in synovium of arthritis.
CONCLUSIONS: These observations confirm the relief of rheumatoid arthritis by baicalin. Our results indicate the effect is related with the modulation of decreased proinflammatory cytokines and inflammatory markers. And the apoptosis promotion of monocytes in synovial fluid were also inhibited. Moreover, the molecular mechanism implies suppressed JAK1/STAT3 signaling with baicalin treatment.
Keywords: Arthritis, Rheumatoid, Drugs, Chinese Herbal, Janus Kinase 1, STAT3 Transcription Factor