Abstract:
: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-α) 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.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Zhao M,Li F,Jian Y,Wang X,Yang H,Wang J,Su J,Lu X,Xi M,Wen A,Li Jdoi
10.1016/j.ejphar.2020.172916subject
Has Abstractpub_date
2020-03-15 00:00:00pages
172916eissn
0014-2999issn
1879-0712pii
S0014-2999(20)30008-Xjournal_volume
871pub_type
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