Glycyrrhizin ameliorates impaired glucose metabolism and ovarian dysfunction in a polycystic ovary syndrome mouse model
Glycyrrhizin ameliorates impaired glucose metabolism and ovarian dysfunction in a polycystic ovary syndrome mouse model
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DOI：
10.1093/biolre/ioad048
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发表时间：
2023-04
影响因子：
3.6
通讯作者：
J. Yang;Amin Ullah;Yangshen Su;A. Otoo;Enoch Appiah Adu-Gyamfi;Qian Feng;Ying-Xiong Wang;Meijiao Wang;Yuchun Ding
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文献类型：
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作者：
J. Yang;Amin Ullah;Yangshen Su;A. Otoo;Enoch Appiah Adu-Gyamfi;Qian Feng;Ying-Xiong Wang;Meijiao Wang;Yuchun Ding
摘要 本研究的目的是确定高迁移率族蛋白 1 抑制剂甘草甜素对多囊卵巢综合征小鼠葡萄糖代谢紊乱和卵巢功能障碍的影响。我们通过使用脱氢表雄酮加高脂肪饮食建立了多囊卵巢综合征小鼠模型。将甘草甜素（100 mg/kg）腹腔注射到多囊卵巢综合征小鼠体内，研究其对体重、糖耐量、胰岛素敏感性、动情周期、激素水平、卵巢病理、糖脂代谢的影响以及一些分子机制。甘草甜素可逆转多囊卵巢综合征小鼠中囊泡数量增加、激素紊乱、糖耐量受损和胰岛素敏感性降低的情况。多囊卵巢综合征小鼠血清和卵巢组织中增加的高迁移率族蛋白1水平也被甘草甜素降低。此外，甘草甜素还可以恢复多囊卵巢综合征小鼠中 Toll 样受体 9、骨髓分化因子 88 和核因子 kappa B 表达的增加，以及胰岛素受体、磷酸化蛋白激酶 B 和葡萄糖转运蛋白 4 型表达的减少。甘草酸可以抑制多囊卵巢综合征引起的高迁移率族蛋白1、多种炎症标志物基因和Toll样受体9/骨髓分化因子88/核因子κB通路的上调，同时抑制胰岛素受体/磷酸化蛋白激酶B/葡萄糖转运蛋白4型通路。因此，甘草甜素是一种有前途的治疗多囊卵巢综合征的药物。摘要 甘草甜素可通过抑制高迁移率族蛋白1的表达，改善多囊卵巢综合征小鼠的炎症、糖代谢紊乱和卵巢功能障碍。
Abstract The aim of this study was to determine the impact of glycyrrhizin, an inhibitor of high mobility group box 1, on glucose metabolic disorders and ovarian dysfunction in mice with polycystic ovary syndrome. We generated a polycystic ovary syndrome mouse model by using dehydroepiandrosterone plus high-fat diet. Glycyrrhizin (100 mg/kg) was intraperitoneally injected into the polycystic ovary syndrome mice and the effects on body weight, glucose tolerance, insulin sensitivity, estrous cycle, hormone profiles, ovarian pathology, glucolipid metabolism, and some molecular mechanisms were investigated. Increased number of cystic follicles, hormonal disorders, impaired glucose tolerance, and decreased insulin sensitivity in the polycystic ovary syndrome mice were reverted by glycyrrhizin. The increased high mobility group box 1 levels in the serum and ovarian tissues of the polycystic ovary syndrome mice were also reduced by glycyrrhizin. Furthermore, increased expressions of toll-like receptor 9, myeloid differentiation factor 88, and nuclear factor kappa B as well as reduced expressions of insulin receptor, phosphorylated protein kinase B, and glucose transporter type 4 were restored by glycyrrhizin in the polycystic ovary syndrome mice. Glycyrrhizin could suppress the polycystic ovary syndrome-induced upregulation of high mobility group box 1, several inflammatory marker genes, and the toll-like receptor 9/myeloid differentiation factor 88/nuclear factor kappa B pathways, while inhibiting the insulin receptor/phosphorylated protein kinase B/glucose transporter type 4 pathways. Hence, glycyrrhizin is a promising therapeutic agent against polycystic ovary syndrome. Summary Sentence Glycyrrhizin could improve inflammation, glucose metabolic disorders, and ovarian dysfunction in polycystic ovary syndrome mice by inhibiting the expression of high mobility group box 1.