Neuritogenic steroid glycosides from crown-of-thorns starfish: Possible involvement of p38 mitogen-activated protein kinase and attenuation of cognitive impairment in senescence-accelerated mice (SAMP8) by peripheral administration.
Neuritogenic steroid glycosides from crown-of-thorns starfish: Possible involvement of p38 mitogen-activated protein kinase and attenuation of cognitive impairment in senescence-accelerated mice (SAMP8) by peripheral administration.
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DOI：
10.1016/j.bmc.2022.117144
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发表时间：
2022-12
影响因子：
3.5
通讯作者：
Yumi Sasayama;T. Mamiya;J. Qi;T. Shibata;K. Uchida;T. Nabeshima;M. Ojika
中科院分区：
文献类型：
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作者：
Yumi Sasayama;T. Mamiya;J. Qi;T. Shibata;K. Uchida;T. Nabeshima;M. Ojika
新的甾体糖苷，acanthasterosides A1，B1和B3，已被分离出的冠的刺海星海星planci。在大鼠嗜铬细胞瘤细胞系PC 12中，具有两个分离的木糖的刺五加皂苷B1和B3诱导神经突生长，就像神经生长因子（NGF）一样，而具有一个木糖的刺五加皂苷A1不诱导神经突生长。刺五加皂苷B3诱导的轴突发生通过显着激活p38丝裂原活化蛋白激酶后，小G蛋白Cdc 42，而不是通过Ras-MEK-ERK途径，主要是由NGF激活。皮下给药后，刺五加皂苷B3在两种不同的认知测试中减轻了加速衰老小鼠（SAMP 8）的认知障碍。液相色谱-质谱辅助定量分析表明，刺五加皂苷B3可通过小鼠循环系统转运至脑内。因此，刺五加皂苷B3（可能还有B1）是一类新的潜在候选药物，用于治疗神经退行性疾病。
Novel steroid glycosides, acanthasterosides A1, B1, and B3, have been isolated from the crown-of-thorns starfishAcanthaster planci. Acanthasterosides B1 and B3 having two separated xyloses induced neurite outgrowth as like as nerve growth factor (NGF) in the rat pheochromocytoma cell line PC12, whereas acanthasteroside A1, having one xylose, did not induce neurite outgrowth. The acanthasteroside B3 induced neuritogenesis via the significant activation of p38 mitogen-activated protein kinase after the activation of the small G-protein Cdc42 rather than via Ras–MEK–ERK pathway that is predominantly activated by NGF. Following subcutaneous administration, acanthasteroside B3 attenuated cognitive impairment of senescence-accelerated mice (SAMP8) in two different cognitive tests. Liquid chromatography–mass spectrometry-assisted quantitative analysis demonstrated that acanthasteroside B3 could be transported into the brain via the circulatory system in mice. Thus, acanthasteroside B3 (and possibly B1) are a novel class of potential drug candidates for neurodegenerative diseases.