1. Academic Validation
  2. Paeoniflorin-6'-o-benzene sulfonate (CP-25) improves vasculitis through inhibiting IL-17A/JAK/STAT3 signaling pathway in endothelial cells of HFD CIA rats

Paeoniflorin-6'-o-benzene sulfonate (CP-25) improves vasculitis through inhibiting IL-17A/JAK/STAT3 signaling pathway in endothelial cells of HFD CIA rats

  • Phytother Res. 2021 Feb;35(2):1033-1047. doi: 10.1002/ptr.6870.
Xiao-Yu Cai 1 Jing-Ru Ge 1 Li Xu 1 Fa-Qin Liang 1 Yue Zhu 1 Yu Tai 1 Xian-Zheng Zhang 1 Jin-Ling Shu 1 Dan Mei 1 Le Han 1 Chen Wang 1 Xiao-Yu Tang 1 Ling-Ling Zhang 1 Wei Wei 1
Affiliations

Affiliation

  • 1 Key Laboratory of Anti-Inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-Inflammatory and Immune Medicine, Institute of Clinical Pharmacology, Anhui Medical University, Hefei, China.
Abstract

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.

Keywords

IL-17A; JAK/STAT3 signaling pathway; cardiovascular diseases; endothelial cell activation; paeoniflorin-6′-o-benzene sulfonate; rheumatoid arthritis.

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