Therapeutic effect of Cryptotanshinone on experimental rheumatoid arthritis through downregulating p300 mediated-STAT3 acetylation

Biochemical Pharmacology
Ying WangLiang Liu

Abstract

The balance between T helper 17 (Th17) cells and regulatory T (Treg) cells, plays a critical role in rheumatoid arthritis (RA). The differentiation of Th17 cells requires the activation of STAT3, which determines the balance of Th17/Treg. Here, we investigated the therapeutic effect of Cryptotanshinone (CTS) on collagen induced mouse arthritis and explored the underlying mechanisms. Arthritis was induced in DBA/1 mice with bovine collagen type II and complete Freund's adjuvant. CTS was given at 20mgkg(-1)d(-1) or 60mgkg(-1)d(-1) by gavage for 6weeks. The immuno-inflammation and joint destruction were evaluated and the balance of Th17/Treg was determined. STAT3 acetylation and phosphorylation were detected by western blotting, and the involvement of p300 was investigated by siRNA and plasmid overexpression. CTS at a dose of 60mgkg(-1)d(-1) ameliorated the inflammation and joint destruction in CIA mice. It improved Th17/Treg imbalance, and inhibited both acetylation and phosphorylation of STAT3. CTS reduced p300 expression and its binding to STAT3, but increased phosphorylated AMPK. Knockdown of p300 mimicked the inhibitory effect of CTS on STAT3 acetylation and phosphorylation, which could be partially rescued by overexpression ...Continue Reading

Citations

Jul 27, 2018·Annals of the Rheumatic Diseases·Shengwei JinJianguang Wang
Aug 15, 2019·Cell Communication and Signaling : CCS·Yuan XiangXing-Hua Liao
Sep 14, 2019·Phytotherapy Research : PTR·Xu-Zhao Li, Shuai-Nan Zhang
Feb 7, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Huayao LiJibiao Wu
Apr 28, 2021·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Celia María Quiñonez-FloresSusana Aideé González-Chávez
May 26, 2021·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·P SivasakthiP Senthamil Selvan

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