脂蛋白脂酶(Lipoprotein lipase,LPL)是脂质代谢的关键酶,其正常调控对于机体向组织提供脂质营养至关重要。作为LPL重要的调控因子,糖基化磷脂酰肌醇锚定高密度脂蛋白结合蛋白1(Glycosylphosphatidylinositol-anchored high density lip...脂蛋白脂酶(Lipoprotein lipase,LPL)是脂质代谢的关键酶,其正常调控对于机体向组织提供脂质营养至关重要。作为LPL重要的调控因子,糖基化磷脂酰肌醇锚定高密度脂蛋白结合蛋白1(Glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1,GPIHBP1)能与LPL结合起脂解平台的作用,并作为载体参与LPL向毛细血管内皮细胞的转运。另外,近年来也鉴定出其他几个LPL活性调控因子,包括microRNAs、A型重复排序蛋白相关受体(Sortilin-related receptor with A-type repeats,SorLA)和载脂蛋白(Apolipoproteins,apo)。这些LPL调控因子的成功鉴定,有助于人们深入认识机体脂解代谢和乳糜微粒血症发生的内在机制。文章重点综述了LPL的调控因子GPIHBP1的研究进展,同时也对其他几个调控因子的研究进展进行了讨论。展开更多
In order to clarify the mechanism of action of licorice flavonoids in alleviating bone loss caused by osteoporosis,this study compared the effects of four glycyrrhiza flavonoids,naringenin,liquiritigenin,isoliquiritig...In order to clarify the mechanism of action of licorice flavonoids in alleviating bone loss caused by osteoporosis,this study compared the effects of four glycyrrhiza flavonoids,naringenin,liquiritigenin,isoliquiritigenin,and licochalcone A,on osteogenic differentiation and mineralization by molecular docking simulation,alkaline phosphatase(ALP)activity and osteocalcin(OCN)content assays,and Runt-related transcription factor 2(Runx2)expression,and explored their potential molecular mechanisms.The results of molecular docking showed that the docking score of liquiritigenin with the estrogen receptor(ER)was the highest.All four flavonoids up-regulated ALP activity and OCN concentration in MC3T3-E1 cells,thereby elevating the mineralization level,among which liquiritigenin was the most effective.Moreover,treatment with a phosphatidylinositol-3-kinase(PI3K)inhibitor(LY294002)inhibited liquiritigenin from inducing increased phosphorylation levels in the PI3K/protein kinase B(AKT)signaling pathway and up-regulation of Runx2 expression,suggesting that PI3K and AKT were involved in osteogenic action.Liquiritigenin reversed bone mineral density loss in a zebrafish osteoporosis model.These findings suggest that liquiritigenin has the most significant osteogenic effect among the four estrogen-like flavonoids,stimulating osteoblast differentiation and bone mineralization through the activation of Runx2 via the PI3K/AKT signaling pathways.In conclusion,this study highlights the great potential of liquiritigenin for preventing and treating osteoporosis.展开更多
文摘脂蛋白脂酶(Lipoprotein lipase,LPL)是脂质代谢的关键酶,其正常调控对于机体向组织提供脂质营养至关重要。作为LPL重要的调控因子,糖基化磷脂酰肌醇锚定高密度脂蛋白结合蛋白1(Glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1,GPIHBP1)能与LPL结合起脂解平台的作用,并作为载体参与LPL向毛细血管内皮细胞的转运。另外,近年来也鉴定出其他几个LPL活性调控因子,包括microRNAs、A型重复排序蛋白相关受体(Sortilin-related receptor with A-type repeats,SorLA)和载脂蛋白(Apolipoproteins,apo)。这些LPL调控因子的成功鉴定,有助于人们深入认识机体脂解代谢和乳糜微粒血症发生的内在机制。文章重点综述了LPL的调控因子GPIHBP1的研究进展,同时也对其他几个调控因子的研究进展进行了讨论。
文摘In order to clarify the mechanism of action of licorice flavonoids in alleviating bone loss caused by osteoporosis,this study compared the effects of four glycyrrhiza flavonoids,naringenin,liquiritigenin,isoliquiritigenin,and licochalcone A,on osteogenic differentiation and mineralization by molecular docking simulation,alkaline phosphatase(ALP)activity and osteocalcin(OCN)content assays,and Runt-related transcription factor 2(Runx2)expression,and explored their potential molecular mechanisms.The results of molecular docking showed that the docking score of liquiritigenin with the estrogen receptor(ER)was the highest.All four flavonoids up-regulated ALP activity and OCN concentration in MC3T3-E1 cells,thereby elevating the mineralization level,among which liquiritigenin was the most effective.Moreover,treatment with a phosphatidylinositol-3-kinase(PI3K)inhibitor(LY294002)inhibited liquiritigenin from inducing increased phosphorylation levels in the PI3K/protein kinase B(AKT)signaling pathway and up-regulation of Runx2 expression,suggesting that PI3K and AKT were involved in osteogenic action.Liquiritigenin reversed bone mineral density loss in a zebrafish osteoporosis model.These findings suggest that liquiritigenin has the most significant osteogenic effect among the four estrogen-like flavonoids,stimulating osteoblast differentiation and bone mineralization through the activation of Runx2 via the PI3K/AKT signaling pathways.In conclusion,this study highlights the great potential of liquiritigenin for preventing and treating osteoporosis.
