State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming 650201, People's Republic of China.
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming 650201, People's Republic of China; University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China.
Bioorg Chem. 2021 Mar;108:104683. doi: 10.1016/j.bioorg.2021.104683. Epub 2021 Jan 27.
The EtOH extracts of the dried seeds of Alpinia katsumadai were revealed with hypoglycemic effects on db/db mice at the concentration of 200 mg/kg. In order to clarify the antidiabetic constituents, 16 new diarylheptanoid-chalcone hybrids, katsumadainols A-A (1-16), together with 13 known analogues (17-29), were isolated from A. katsumadai under the guidance of bioassay. Most of the compounds showed α-glucosidase and PTP1B dual inhibition, among which compounds 1-3, 5-7, 11-14, 21-25, and 27 showed PTP1B/TCPTP selective inhibition with IC values ranging from 22.0 to 96.7 μM, which were 2-10 times more active than sodium orthovanadate (IC, 215.7 μM). All compounds exhibited obvious inhibition against α-glucosidase with IC values of 2.9-29.5 μM, indicating 6-59 times more active than acarbose (IC, 170.9 μM). Study of enzyme kinetics indicated compounds 1, 3, and 12 were PTP1B and α-glucosidase mixed-type inhibitors with K values of 13.1, 12.9, 21.6 μM, and 4.9, 7.4, 3.4 μM, respectively.
高良姜种子的 EtOH 提取物在浓度为 200mg/kg 时对 db/db 小鼠显示出降血糖作用。为了阐明抗糖尿病成分，在生物测定的指导下，从高良姜中分离得到了 16 种新的二芳基庚烷-查尔酮杂合体，即高良姜醇 A-A（1-16），以及 13 种已知类似物（17-29）。大多数化合物表现出α-葡萄糖苷酶和 PTP1B 双重抑制作用，其中化合物 1-3、5-7、11-14、21-25 和 27 对 PTP1B/TCPTP 具有选择性抑制作用，IC 值范围为 22.0-96.7μM，比正钒酸钠（IC，215.7μM）活性高 2-10 倍。所有化合物对α-葡萄糖苷酶均表现出明显的抑制作用，IC 值为 2.9-29.5μM，比阿卡波糖（IC，170.9μM）活性高 6-59 倍。酶动力学研究表明，化合物 1、3 和 12 是 PTP1B 和α-葡萄糖苷酶的混合抑制剂，K 值分别为 13.1、12.9 和 21.6μM，以及 4.9、7.4 和 3.4μM。
