PMID- 31930970
OWN - NLM
STAT- MEDLINE
DCOM- 20201127
LR  - 20201127
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 871
DP  - 2020 Mar 15
TI  - Salvianolic acid B regulates macrophage polarization in ischemic/reperfused 
      hearts by inhibiting mTORC1-induced glycolysis.
PG  - 172916
LID - S0014-2999(20)30008-X [pii]
LID - 10.1016/j.ejphar.2020.172916 [doi]
AB  - Macrophages play important roles in the healing and remodeling of cardiac tissues 
      after myocardial ischemia/reperfusion (MI/R) injury. Here we investigated the 
      potential effects of salvianolic acid B (SalB), one of the abundant and bioactive 
      compounds extracted from Chinese herb Salvia Miltiorrhiza (Danshen), on 
      macrophage-mediated inflammation after MI/R and the underlying mechanisms. In 
      primary cultured bone marrow-derived macrophages (BMDMs), SalB attenuated 
      lipopolysaccharide (LPS)-induced M1 biomarkers (IL-6, iNOS, CCL2 and TNF-alpha) mRNA 
      expression in a concentration-dependent manner. In contrast, M2 biomarkers (Arg1, 
      Clec10a and Mrc) mRNA levels following interleukinin-4 (IL-4) stimulation were 
      significantly upregulated by SalB. In addition, LPS stimulation potently induced 
      transcriptional upregulation of RagD, an important activation factor of mammalian 
      target of rapamycin complex 1 (mTORC1). Interestingly, SalB inhibited RagD 
      upregulation and mTORC1 activation, decreased glycolysis, and reduced 
      inflammatory cytokine production in LPS-stimulated macrophages, all of which were 
      blunted in RagD knockdown macrophages. In mice subjected to MI/R, SalB treatment 
      decreased cardiac M1-macrophages and increased M2-macrophages at 3 days 
      post-MI/R, followed by decreased collagen deposition and ameliorated cardiac 
      dysfunction at 7 days post-MI/R. Collectively, our data have shown that SalB 
      decreases M1-polarized macrophages in MI/R hearts via inhibiting mTORC1-dependent 
      glycolysis, which might contribute to alleviated inflammation and improved 
      cardiac dysfunction afforded by SalB after MI/R.
CI  - Copyright (c) 2020 Elsevier B.V. All rights reserved.
FAU - Zhao, Meina
AU  - Zhao M
AD  - Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, 
      Xi'an, Shaanxi, 710032, China; College of Pharmacy, Shaanxi University of Chinese 
      Medicine, Xianyang, Shaanxi, 712046, China.
FAU - Li, Fei
AU  - Li F
AD  - Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, 
      Xi'an, Shaanxi, 710032, China.
FAU - Jian, Yufan
AU  - Jian Y
AD  - Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, 
      Xi'an, Shaanxi, 710032, China.
FAU - Wang, Xinpei
AU  - Wang X
AD  - School of Aerospace Medicine, Fourth Military Medical University, Xi'an, 710032, 
      China.
FAU - Yang, Hongyan
AU  - Yang H
AD  - School of Aerospace Medicine, Fourth Military Medical University, Xi'an, 710032, 
      China.
FAU - Wang, Jun
AU  - Wang J
AD  - Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, 
      Xi'an, Shaanxi, 710032, China; Department of Anesthesiology, Shaanxi Armed Police 
      Corps Hospital, Xi'an, Shaanxi, 710054, China.
FAU - Su, Jing
AU  - Su J
AD  - Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, 
      Xi'an, Shaanxi, 710032, China.
FAU - Lu, Xinming
AU  - Lu X
AD  - YouYi Clinical Laboratories of Shaanxi, Xi'an, Shaanxi, 710065, China.
FAU - Xi, Miaomiao
AU  - Xi M
AD  - Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, 
      Xi'an, Shaanxi, 710032, China; TANK Medicinal Biology Institute of Xi'an, Xi'an, 
      Shaanxi, 710032, China. Electronic address: miaomiaoxi2014@163.com.
FAU - Wen, Aidong
AU  - Wen A
AD  - Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, 
      Xi'an, Shaanxi, 710032, China. Electronic address: adwen-2004@hotmail.com.
FAU - Li, Jia
AU  - Li J
AD  - School of Aerospace Medicine, Fourth Military Medical University, Xi'an, 710032, 
      China. Electronic address: jiali816@fmmu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20200110
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Benzofurans)
RN  - C1GQ844199 (salvianolic acid B)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
SB  - IM
MH  - Animals
MH  - Benzofurans/*pharmacology
MH  - Glycolysis/drug effects
MH  - Heart/*drug effects/physiopathology
MH  - Macrophage Activation
MH  - Macrophages/cytology/*drug effects/immunology
MH  - Mechanistic Target of Rapamycin Complex 1/*metabolism
MH  - Mice
MH  - Myocardial Reperfusion Injury/*immunology/*metabolism/physiopathology
OTO - NOTNLM
OT  - MTORC1
OT  - Macrophage polarization
OT  - Myocardial ischemia/reperfusion injury
OT  - Salvianolic acid B
COIS- Declaration of competing interest All authors have reported that they have no 
      relationships relevant to the contents of this paper to disclose.
EDAT- 2020/01/14 06:00
MHDA- 2020/11/28 06:00
CRDT- 2020/01/14 06:00
PHST- 2019/03/01 00:00 [received]
PHST- 2019/12/23 00:00 [revised]
PHST- 2020/01/09 00:00 [accepted]
PHST- 2020/01/14 06:00 [pubmed]
PHST- 2020/11/28 06:00 [medline]
PHST- 2020/01/14 06:00 [entrez]
AID - S0014-2999(20)30008-X [pii]
AID - 10.1016/j.ejphar.2020.172916 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2020 Mar 15;871:172916. doi: 10.1016/j.ejphar.2020.172916. Epub 
      2020 Jan 10.