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人参茎叶总皂苷碱水解产物中的新型SIRT1激活剂。

New SIRT1 activator from alkaline hydrolysate of total saponins in the stems-leaves of Panax ginseng.

作者信息

Ma Li-Yuan, Zhou Qi-Le, Yang Xiu-Wei

机构信息

State Key Laboratory of Natural and Biomimetic Drugs (Peking University), Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University Health Science Center, Peking University, No. 38, Xueyuan Road, Haidian District, Beijing 100191, PR China.

State Key Laboratory of Natural and Biomimetic Drugs (Peking University), Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University Health Science Center, Peking University, No. 38, Xueyuan Road, Haidian District, Beijing 100191, PR China.

出版信息

Bioorg Med Chem Lett. 2015 Nov 15;25(22):5321-5. doi: 10.1016/j.bmcl.2015.09.039. Epub 2015 Sep 15.

DOI:10.1016/j.bmcl.2015.09.039
PMID:26420067
Abstract

Two new dammarane-type triterpenes, namely ginsenoslaloside-I [3β,12β,24S-trihydroxy-dammara-20(22)E,25-diene-3-O-β-D-glucopyranoside, 1] and 20(S)-ginsenoside-Rh1-6'-acetate (2), together with twelve known compounds (3-14) were isolated from the alkaline hydrolysate of total saponins of the stems-leaves of Panax ginseng C.A. Meyer. Their chemical structures were elucidated by extensive spectroscopic analyses and comparison with the reported data. All 14 compounds were evaluated for their anti-proliferative activities against two human cancer cell lines (HL-60 and Hep-G2) and promotion activities of SIRT1. Compound 6 exhibited significant inhibitory activity in a concentration-dependent manner against HL-60 and Hep-G2 with the IC50 values of 10.32 and 24.33μM, respectively, and had comparable IC50 values with those of vinorelbine, a positive control agent. Meanwhile, compounds 1 and 6 were found to be a potential activator of SIRT1. The preliminary structure-activity relationship was also discussed based on the experimental data obtained.

摘要

从人参(Panax ginseng C.A. Meyer)茎叶总皂苷的碱性水解产物中分离得到两种新的达玛烷型三萜,即人参皂苷laoside-I [3β,12β,24S-三羟基-达玛-20(22)E,25-二烯-3-O-β-D-吡喃葡萄糖苷,1] 和20(S)-人参皂苷-Rh1-6'-乙酸酯 (2),以及12种已知化合物 (3 - 14)。通过广泛的光谱分析并与报道数据进行比较,阐明了它们的化学结构。对所有14种化合物进行了针对两种人类癌细胞系(HL-60和Hep-G2)的抗增殖活性以及SIRT1促进活性的评估。化合物6对HL-60和Hep-G2表现出显著的浓度依赖性抑制活性,IC50值分别为10.32和24.33μM,且与阳性对照药长春瑞滨的IC50值相当。同时,发现化合物1和6是SIRT1的潜在激活剂。还基于所获得的实验数据讨论了初步的构效关系。

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