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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2019.00850

Tanshinone IIA Exerts Anti-inflammatory and Immune-regulating Effects on Vulnerable Atherosclerotic Plaque Partially via TLR4/MyD88/NF-κB Signal Pathway

 Zhuo Chen1,  xiang gao2, yang jiao1, yu qiu1,  anlu wang3,  meili yu4, fangyuan che5, siming li1, jing liu6,  jingen li7,  he zhang3, changan yu8, geng li8, yanxiang gao8,  lin pan8,  weiliang sun8,  Jing Guo8, binyan cao1,  yilin zhu9 and  hao xu1*
  • 1Xiyuan Hospital, China
  • 2Tieying Hospital of Fengtai District Beijing, China
  • 3Beijing University of Chinese Medicine, China
  • 4Beijing First Hospital of Integrated Traditional Chinese and Western Medicine, China
  • 5Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, China
  • 6China Academy of Chinese Medical Sciences, China
  • 7Dongzhimen Hospital, Beijing University of Chinese Medicine, China
  • 8China-Japan Friendship Hospital, China
  • 9Wangjing Hospital of China Academy of Chinese Medical Sciences, China

Background— Tanshinone IIA (Tan IIA), a lipophilic constituent from Salvia miltiorrhiza Bunge, has shown a promising cardioprotective effect including anti-atherosclerosis. This study aims at exploring Tan IIA’s anti-inflammatory and immune-regulating roles in stabilizing vulnerable atherosclerotic plaque in ApoE deficient (ApoE-/-) mice.
Methods— Male ApoE-/- mice (6 weeks) were fed with high fat diet for 13 weeks and then randomized to model group (MOD) or Tan IIA groups [high dose: 90 mg/kg/day (HT), moderate dose: 30 mg/kg/day (MT), low dose: 10 mg/kg/day (LT)] or atorvastatin group (5mg/kg/day, ATO) for 13 weeks. Male C57BL/6 mice (6 weeks) were fed with ordinary rodent chow as control. The plaque stability was evaluated according to the morphology and composition of aortic atherosclerotic (AS) plaque in H&E staining and Movat staining sections by calculating the area of extracellular lipid, collagenous fiber and foam cells to the plaque. The expression of Toll-like receptor 4 (TLR4)/ myeloid differentiation factor88 (MyD88)/ nuclear factor-kappa B (NF-κB) signal pathway in aorta fractions was determined by immunohistochemistry. Serum level of blood lipid were measured by turbidimetric inhibition immunoassay. The concentrations of tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) were detected by cytometric bead array. Results— Tan ⅡA stabilized aortic plaque with a striking reduction in the area of extracellular lipid (ATO: 13.15±1.2%, HT: 12.2±1.64%, MT: 13.93±1.59%, MOD: 18.84±1.46%, P<0.05) or foam cells (ATO: 16.05±1.26%, HT: 14.88±1.79%, MT: 16.61±1.47%, MOD: 22.08±1.69%, P<0.05) to the plaque, and an evident increase in content of collagenous fiber (ATO: 16.22±1.91%, HT: 17.58±1.33%, MT: 15.71±2.26%, LT:14.92±1.65%, MOD: 9.61±0.7%, P<0.05) to the plaque than that in the model group, concomitant with down-regulation of the protein expression of TLR4, MyD88 and NF-κB p65, and serum level of MCP-1, TNF-α in a dose-dependent manner. There were no differences in serum TC, LDL, HDL or TG levels between ApoE–/– mice and that treated with atorvastatin.Conclusions—These results suggest Tan IIA could stabilize vulnerable AS plaque in ApoE-/- mice and this anti-inflammatory and immune-regulating effect may been achieved via TLR4/MyD88/NF-κB signaling pathway.

Keywords: tanshinone IIA, Atherosclerosis, anti-inflammatory, Immune Regulation, TLR4/MyD88/NF-κB

Received: 27 Jan 2019; Accepted: 03 Jul 2019.

Edited by:

Chrishan S. Samuel, Department of Pharmacology, Monash University, Australia

Reviewed by:

Brad R. Broughton, Monash University, Australia
Antony Vinh, Department of Physiology, Anatomy and Microbiology, La Trobe University, Australia  

Copyright: © 2019 Chen, gao, jiao, qiu, wang, yu, che, li, liu, li, zhang, yu, li, gao, pan, sun, Guo, cao, zhu and xu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. hao xu, Xiyuan Hospital, Beijing, China, xuhaotcm@hotmail.com