PMID- 31402870
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 10
DP  - 2019
TI  - Tanshinone IIA Exerts Anti-Inflammatory and Immune-Regulating Effects on 
      Vulnerable Atherosclerotic Plaque Partially via the TLR4/MyD88/NF-kappaB Signal 
      Pathway.
PG  - 850
LID - 10.3389/fphar.2019.00850 [doi]
LID - 850
AB  - 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 a high-fat diet for 13 weeks and then randomized to the 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 the atorvastatin group (5 mg/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 the Toll-like receptor 4 (TLR4)/myeloid 
      differentiation factor88 (MyD88)/nuclear factor-kappa B (NF-kappaB) signal pathway in 
      aorta fractions was determined by immunohistochemistry. Serum levels of blood 
      lipid were measured by turbidimetric inhibition immunoassay. The concentrations 
      of tumor necrosis factor-alpha (TNF-alpha) 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-kappaB p65, and 
      serum level of MCP-1 and TNF-alpha in a dose-dependent manner. There were no 
      differences in serum TC, LDL, HDL, or TG levels between ApoE(-/-) mice and those 
      treated with atorvastatin. Conclusions: These results suggest that Tan IIA could 
      stabilize vulnerable AS plaque in ApoE(-/-) mice, and this anti-inflammatory and 
      immune-regulating effect may be achieved via the TLR4/MyD88/NF-kappaB signaling 
      pathway.
FAU - Chen, Zhuo
AU  - Chen Z
AD  - Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
FAU - Gao, Xiang
AU  - Gao X
AD  - Internal medicine, Tieying Hospital of Fengtai District, Beijing, China.
FAU - Jiao, Yang
AU  - Jiao Y
AD  - Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
FAU - Qiu, Yu
AU  - Qiu Y
AD  - Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
FAU - Wang, Anlu
AU  - Wang A
AD  - Graduate School, Beijing University of Chinese Medicine, Beijing, China.
FAU - Yu, Meili
AU  - Yu M
AD  - Beijing First Hospital of Integrated Chinese and Western Medicine, Beijing, 
      China.
FAU - Che, Fangyuan
AU  - Che F
AD  - Cardiovascular Department, Beijing hospital of Traditional Chinese Medicine 
      Shunyi branch, Beijing, China.
FAU - Li, Siming
AU  - Li S
AD  - Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
FAU - Liu, Jing
AU  - Liu J
AD  - Graduate school, China Academy of Chinese Medical, Beijing, China.
FAU - Li, Jingen
AU  - Li J
AD  - Dongzhimen Hospital, The First Affiliated Hospital of Beijing University of 
      Chinese Medicine, Beijing, China.
FAU - Zhang, He
AU  - Zhang H
AD  - Graduate School, Beijing University of Chinese Medicine, Beijing, China.
FAU - Yu, Changan
AU  - Yu C
AD  - China-Japan Friendship Hospital, Beijing, China.
FAU - Li, Geng
AU  - Li G
AD  - China-Japan Friendship Hospital, Beijing, China.
FAU - Gao, Yanxiang
AU  - Gao Y
AD  - China-Japan Friendship Hospital, Beijing, China.
FAU - Pan, Lin
AU  - Pan L
AD  - China-Japan Friendship Hospital, Beijing, China.
FAU - Sun, Weiliang
AU  - Sun W
AD  - China-Japan Friendship Hospital, Beijing, China.
FAU - Guo, Jing
AU  - Guo J
AD  - China-Japan Friendship Hospital, Beijing, China.
FAU - Cao, Bingyan
AU  - Cao B
AD  - Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
FAU - Zhu, Yilin
AU  - Zhu Y
AD  - Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
FAU - Xu, Hao
AU  - Xu H
AD  - Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
LA  - eng
PT  - Journal Article
DEP - 20190726
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC6677033
OTO - NOTNLM
OT  - TLR4/MyD88/NF-kappaB
OT  - Tanshinone IIA
OT  - anti-inflammatory
OT  - atherosclerosis
OT  - immune regulation
EDAT- 2019/08/14 06:00
MHDA- 2019/08/14 06:01
PMCR- 2019/07/26
CRDT- 2019/08/13 06:00
PHST- 2019/01/27 00:00 [received]
PHST- 2019/07/03 00:00 [accepted]
PHST- 2019/08/13 06:00 [entrez]
PHST- 2019/08/14 06:00 [pubmed]
PHST- 2019/08/14 06:01 [medline]
PHST- 2019/07/26 00:00 [pmc-release]
AID - 10.3389/fphar.2019.00850 [doi]
PST - epublish
SO  - Front Pharmacol. 2019 Jul 26;10:850. doi: 10.3389/fphar.2019.00850. eCollection 
      2019.