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Ability of Post-treatment Glycyrrhizic Acid to Mitigate Cerebral Ischemia/Reperfusion Injury in Diabetic Mice

Yuan Li, Na Yao, Ting Zhang, Fengying Guo, Xiangying Niu, Zhihui Wu, Shaozhang Hou

School of Nursing, Ningxia Medical University, Yinchuan, Ningxia, China (mainland)

Med Sci Monit 2020; 26:e926551

DOI: 10.12659/MSM.926551

Available online: 2020-08-10

Published: 2020-09-28

BACKGROUND: Diabetes aggravates cerebral ischemia/reperfusion (I/R) injury by increasing inflammatory reactions, but its specific mechanism is currently unclear.
MATERIAL AND METHODS: Diabetes was induced in mice with a high-fat diet combined with streptozotocin. These mice were subjected to transient middle cerebral artery occlusion (tMCAO) for 60 min, followed by reperfusion for 24-72 h and post-treatment glycyrrhizic acid (GA). Control and diabetic mice were randomly allocated to 8 groups of 18 mice each. Blood glucose, brain infarction, brain edema, and neurological function were monitored. Necrosis was determined by Nissl staining, loss of neurons by immunofluorescent (IF) staining for NeuN, and activation of inflammatory microglia by IF staining for Iba-1. Levels of HMGB1, TLR4, Myd88, and NF-kappaB mRNA and protein in ischemic brain were determined by qRT-PCR and western blotting, respectively, and serum concentrations of IL-1ß, IL-6, and TNF-alpha by ELISA.
RESULTS: Infarction volume, brain edema, and neurological function after tMCAO were significantly aggravated in diabetes, but ameliorated by post-treatment GA. GA also reduced neuronal loss and microglial activation. Cerebral Myd88 level showed a positive correlation with neurological scores. GA suppressed the expression of Myd88 and a proinflammatory pathway that included Myd88, HMGB1, TLR4, and NF-kappaB, as well as reducing serum concentrations of IL-1ß, IL-6, and TNF-alpha.
CONCLUSIONS: Post-treatment inhibited inflammatory responses and provided therapeutic benefits in diabetic mice with cerebral I/R injury, suggesting that GA may be a candidate drug to suppress cerebral I/R in diabetic patients.

Keywords: Brain Ischemia, Diabetes Mellitus, Type 2, Glycyrrhizic Acid, Inflammation, Myeloid Differentiation Factor 88