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 many important biomedical functions. Our previous studies reported that GLP-1R agonist exenatide promoted M2 polarization and the expression of cell-specific anti-inflammatory factor interleukin-10 in neuropathological pain model. In this study, we proved that morroniside not only induced M2 polarization and stimulated interleukin-10 expression specifically in cortical primary microglia by p38β mitogen-activated protein kinases pathway but also protected nerve cells against H2O2-induced cell oxidative damage and prohibited ischemic injury by reducing infarct size, which is at least in part mediated by enhanced expression of microglial interleukin-10. In the cortical penumbra area in middle cerebral artery occlusion (MCAO) mice. In general, our results indicated that GLP-1R agonist morroniside might play a neuroprotective effect by inducing M2 polarization, and cyclic-AMP/protein kinase A/p38β pathway might mediate morroniside-induced expression of interleukin-10 protein in M2 microglia.
Highlights
Transcriptomic analysis revealed that 75% of differentially expressed genes in ischemic brain tissues were derived from microglia, mainly related to inflammatory factors, cell activity, differentiation and metastasis, and so on (Khan et al, 2017)
Microglial activation is closely related to secondary brain damage induced by ischemic stroke, and its activation can be roughly divided into pro-inflammatory M1 type and anti-inflammatory M2 type, which can be induced to M2a type by interlukin-4 and interlukin-13, or to M2c type by interlukin-10 (IL-10) and glucocorticoids
Our previous study demonstrated that intrathecal injection of glucagon-like peptide-1 receptor (GLP-1R) agonist exenatide (100 ng) significantly enhanced mRNA levels of M2 microglial markers IL-10, IL-4, arginase1 (Arg 1), and cluster of differentiation CD206 in both contralateral/ipsilateral spinal cords of neuropathic rats induced by tight ligation of L5/L6 spinal nerves (Wu et al, 2017a)
Summary
Transcriptomic analysis revealed that 75% of differentially expressed genes in ischemic brain tissues were derived from microglia, mainly related to inflammatory factors, cell activity, differentiation and metastasis, and so on (Khan et al, 2017). Microglial activation is closely related to secondary brain damage induced by ischemic stroke, and its activation can be roughly divided into pro-inflammatory M1 type and anti-inflammatory M2 type, which can be induced to M2a type by interlukin-4 and interlukin-13, or to M2c type by interlukin-10 (IL-10) and glucocorticoids. The latter M2c type is importantly related to neuroprotection and tissue remodeling (Qin et al, 2019). The mechanism of morroniside against ischemic stroke was elucidated as prohibiting neural apoptosis and MMP2/9 expression, enhancing angiogenesis and improving microvascular functional integrity of the neurovascular unit after cerebral ischemia (Sun et al, 2014; Liu et al, 2016; Zeng et al, 2018)
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