AUTHOR=Liu Hao , Ou Mei-Xian , Han Qiao-Qiao TITLE=Microglial M2 Polarization Mediated the Neuroprotective Effect of Morroniside in Transient MCAO-Induced Mice JOURNAL=Frontiers in Pharmacology VOLUME=Volume 12 - 2021 YEAR=2021 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.784329 DOI=10.3389/fphar.2021.784329 ISSN=1663-9812 ABSTRACT=Morroniside, a secoiridoid glycoside from Cornus officinalis, is a class of small molecule non-peptide glucagon-like peptide-1 receptor (GLP-1R) agonists and possess lots of important biomedical functions. Our previous studies reported that GLP-1R agonist exenatide promoted M2 polarization and the expression of cell-specific anti-inflammatory factor IL-10 in neuropathological pain model. In this study, we proved that morroniside not only induced M2 polarization and stimulated IL-10 expression specifically in cortical primary microglia by p38β MAPK pathway, but also protected nerve cells against H2O2-induced cell oxidative damage and prohibited ischemic injury by reducing infarct size, which at least in part mediated by enhanced expression of microglial IL-10 in the cortical penumbra area in MCAO mice. In general, our results indicated that GLP-1R agonist morronisde might play neuroprotective effect by inducing M2 polarization, and cAMP/PKA/p38β pathway might mediate morroniside-induced expression of IL-10 protein in M2 microglia.