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Paeoniflorin‐6′‐o‐benzene sulfonate ( CP ‐25) improves vasculitis through inhibiting IL‐17A / JAK / STAT3 signaling pathway in endothelial cells of HFD CIA rats
Author(s) -
Cai XiaoYu,
Ge JingRu,
Xu Li,
Liang FaQin,
Zhu Yue,
Tai Yu,
Zhang XianZheng,
Shu JinLing,
Mei Dan,
Han Le,
Wang Chen,
Tang XiaoYu,
Zhang LingLing,
Wei Wei
Publication year - 2021
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.6870
Subject(s) - medicine , umbilical vein , human umbilical vein endothelial cell , arthritis , rheumatoid arthritis , vasculitis , immunology , pathogenesis , endothelial dysfunction , endothelial stem cell , stat3 , endocrinology , signal transduction , pharmacology , in vitro , chemistry , biochemistry , disease
Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects not only joints but also multiple organ systems including cardiovascular system. Endothelial dysfunction plays an important role in cardiovascular diseases (CVD). In RA, endothelial dysfunction exists at both the macrovascular and the microvascular levels, which is a precursor to vasculitis. This study aimed to investigate the pathogenesis of vasculitis and the therapeutic effect of CP‐25 on vasculitis in high‐fat diet (HFD) collagen‐induced arthritis (CIA) rats. Experimental groups were divided into normal group, HFD group, CIA group, HFD CIA group, CP‐25 group and MTX group. In vitro, IL‐17A was used to stimulate human umbilical vein endothelial cells (HUVECs), and then CP‐25 was used to intervene. Results showed that CP‐25 reduced global scoring (GS), arthritis index (AI), and swollen joint count (SJC) scores, improved histopathological score, reduced T cells percentage, and decreased IL‐17A and ICAM‐1 levels. Besides, CP‐25 reduced the expression of p‐STAT3 to normal levels in vascular of HFD CIA rats. In vitro, IL‐17A promoted the expression of p‐JAK1, p‐JAK2, p‐JAK3, pSTAT3, and ICAM‐1, and CP‐25 inhibited the expression of p‐JAK1, p‐JAK2, p‐JAK3, p‐STAT3, and ICAM‐1. In conclusion, CP‐25 might inhibit endothelial cell activation through inhibiting IL‐17A/JAK/STAT3 signaling pathway, which improves vasculitis in HFD CIA rats.