Antidiabetic lanostane triterpenoids from the fruiting bodies of Ganoderma weberianum.
Antidiabetic lanostane triterpenoids from the fruiting bodies of Ganoderma weberianum.
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DOI：
10.1016/j.bioorg.2022.106025
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发表时间：
2022-07
影响因子：
5.1
通讯作者：
Li Yang-;Dexian Kong;Na Xiao;Qing-yun Ma;Qing-yi Xie;Jiaocen Guo;Chun Ying Deng;Hai-Xia Ma;Yan Hua;Haofu Dai;You-Xing Zhao
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文献类型：
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作者：
Li Yang-;Dexian Kong;Na Xiao;Qing-yun Ma;Qing-yi Xie;Jiaocen Guo;Chun Ying Deng;Hai-Xia Ma;Yan Hua;Haofu Dai;You-Xing Zhao
从韦氏灵芝（Ganoderma weberianum）子实体中分离得到8个羊毛甾烷三萜化合物（ganodeweberiols A）和1-8个已知化合物（9-26）。新化合物的结构和绝对构型通过广泛的光谱分析，以及NMR化学位移和电子圆二色性（ECD）计算确定。化合物2、7、12和14显示出显著的α-葡萄糖苷酶抑制活性，与阳性对照阿卡波糖（IC 50，304.6 μM）相比，IC 50值范围为35.3 μM至223.4 μM。动力学研究表明，化合物12为α-葡萄糖苷酶的混合型抑制剂。分子对接模拟揭示了12与α-葡萄糖苷酶的相互作用。此外，化合物3和6抑制HepG 2细胞中胰高血糖素诱导的肝葡萄糖产生，EC 50值分别为42.0和85.9 μM。进一步的研究表明化合物3和6通过抑制胰高血糖素诱导的cAMP积累来抑制肝脏葡萄糖的产生。化合物3和化合物26对HeLa细胞有抑制作用，IC_（50）分别为17.0和6.8 μM。
Eight previously undescribed lanostane triterpenoids, ganodeweberiols A ∼ H (1–8), together with eighteen known compounds (9–26), were isolated from the fruiting bodies ofGanoderma weberianum. The structures and absolute configurations of the new compounds were determined by extensive spectroscopic analysis, as well as NMR chemical shifts and electronic circular dichroism (ECD) calculations. Compounds2,7,12, and14showed significantα-glucosidase inhibitory activity with IC50values ranging from 35.3 μM ∼ 223.4 μM compared to the positive control acarbose (IC50, 304.6 μM). Kinetic study indicated that the most potent compound12was a mixed type inhibitor for α-glucosidase. Molecular docking simulation revealed the interactions of12withα-glucosidase. Additionally, Compounds3and6inhibited glucagon-induced hepatic glucose production in HepG2 cells with EC50values of 42.0 and 85.9 μM, respectively. Further study revealed that compounds3and6inhibited hepatic glucose production by suppression glucagon-induced cAMP accumulation. Moreover, compounds3and26were active against HeLa cell line with IC50values of 17.0 and 6.8 μM, respectively.