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
钙调磷酸酶B蛋白(calcineurin B like protein,CBL)是一类植物特有的Ca^(2+)传感器,在植物生长发育和逆境胁迫响应中发挥重要作用。CBL由4个典型的用于Ca^(2+)结合的手性延伸因子(elongation factor hands,EF-hands)结构域构成,并且每个...钙调磷酸酶B蛋白(calcineurin B like protein,CBL)是一类植物特有的Ca^(2+)传感器,在植物生长发育和逆境胁迫响应中发挥重要作用。CBL由4个典型的用于Ca^(2+)结合的手性延伸因子(elongation factor hands,EF-hands)结构域构成,并且每个EF-hand含有12个相对保守氨基酸组成的α-螺旋-环-α-螺旋结构。CBL启动子区域的顺式调控作用元件(如W-box、MBS和G-BOX等)可与上游转录因子(transcription factors,TFs)结合,通过激活或抑制下游基因的表达,从而进行转录调控。CBL通过脱落酸(abscisic acid,ABA)、呼吸爆发氧化酶同源物(respiratory burst oxidases homolog,RBOH)以及活性氧(reactive oxygen species,ROS)等信号通路调控植物气孔运动,减少水分蒸发,以适应各种逆境胁迫。大量研究表明,当植物受到盐、干旱、极端温度、营养胁迫和病原菌等逆境胁迫时,CBL能够迅速感知细胞内瞬时Ca^(2+)信号变化,不仅与CBL互作蛋白激酶(CBL-interacting protein kinase,CIPK)互作磷酸化下游靶标蛋白实现Ca^(2+)信号传导,还与其他蛋白质(如高亲和力K^(+)转运蛋白5、蛋白S-酰化转移酶10和2C类蛋白磷酸酶等)互作,从而正向或负向调控植物的抗逆性。此外,CBL介导植物器官和组织生长发育,通过调节糖信号促进果实成熟。CBL也与开花时间基因(gigantea,GI)结合以影响植物的开花时间。论文综述了植物CBL的发现、结构、分类、调控机制、生物学功能及其调控逆境胁迫响应的作用机制,并对其未来研究方向进行了展望,以期为农作物抗逆性遗传改良和生物育种提供基因资源和理论依据。展开更多
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.
文摘钙调磷酸酶B蛋白(calcineurin B like protein,CBL)是一类植物特有的Ca^(2+)传感器,在植物生长发育和逆境胁迫响应中发挥重要作用。CBL由4个典型的用于Ca^(2+)结合的手性延伸因子(elongation factor hands,EF-hands)结构域构成,并且每个EF-hand含有12个相对保守氨基酸组成的α-螺旋-环-α-螺旋结构。CBL启动子区域的顺式调控作用元件(如W-box、MBS和G-BOX等)可与上游转录因子(transcription factors,TFs)结合,通过激活或抑制下游基因的表达,从而进行转录调控。CBL通过脱落酸(abscisic acid,ABA)、呼吸爆发氧化酶同源物(respiratory burst oxidases homolog,RBOH)以及活性氧(reactive oxygen species,ROS)等信号通路调控植物气孔运动,减少水分蒸发,以适应各种逆境胁迫。大量研究表明,当植物受到盐、干旱、极端温度、营养胁迫和病原菌等逆境胁迫时,CBL能够迅速感知细胞内瞬时Ca^(2+)信号变化,不仅与CBL互作蛋白激酶(CBL-interacting protein kinase,CIPK)互作磷酸化下游靶标蛋白实现Ca^(2+)信号传导,还与其他蛋白质(如高亲和力K^(+)转运蛋白5、蛋白S-酰化转移酶10和2C类蛋白磷酸酶等)互作,从而正向或负向调控植物的抗逆性。此外,CBL介导植物器官和组织生长发育,通过调节糖信号促进果实成熟。CBL也与开花时间基因(gigantea,GI)结合以影响植物的开花时间。论文综述了植物CBL的发现、结构、分类、调控机制、生物学功能及其调控逆境胁迫响应的作用机制,并对其未来研究方向进行了展望,以期为农作物抗逆性遗传改良和生物育种提供基因资源和理论依据。
