He Xiao-Feng, Wu Sheng-Li, Chen Ji-Jun, Hu Jing, Huang Xiao-Yan, Li Tian-Ze, Zhang Xue-Mei, Guo Yuan-Qiang, Geng Chang-An
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; School of Life Sciences, Yunnan University, Kunming 650500, People's Republic of China.
Bioorg Chem. 2022 Mar;120:105653. doi: 10.1016/j.bioorg.2022.105653. Epub 2022 Feb 3.
Ten new diarylheptanoid dimers, katsumadainols C - C (1-10), were isolated from the seeds of Alpinia katsumada and elucidated by extensive spectroscopic methods, ECD calculations, and single-crystal X-ray diffraction. Their antidiabetic effects were evaluated by the stimulation of GLP-1 secretion in STC-1 cells and inhibition against four diabetes-related enzymes, GPa, α-glucosidase, PTP1B, and DPP4. Compounds 1-5 and 7-10 significantly stimulated GLP-1 secretion by 267.5-433.1% (25.0 μM) and 117.8-348.2% (12.5 μM). Compounds 1-4 exhibited significant inhibition on GPa with IC values of 18.0-31.3 μM; compounds 1-5 showed obvious inhibition on α-glucosidase with IC values of 6.9-18.2 μM; compounds 1-5 and 10 possessed PTP1B inhibitory activity with IC values ranging from 35.5 to 80.1 μM. This investigation first disclosed compounds 1-4 as intriguing GLP-1 secretagogues and GPa, α-glucosidase, and PTP1B inhibitors, which provided valuable clues for searching multiple-target antidiabetic candidates from Zingiberaceae plants.
从草豆蔻种子中分离得到10个新的二芳基庚烷二聚体，即草豆蔻醇C - C（1 - 10），并通过广泛的光谱方法、电子圆二色光谱（ECD）计算和单晶X射线衍射对其进行了结构解析。通过检测它们对STC - 1细胞中胰高血糖素样肽-1（GLP - 1）分泌的刺激作用以及对四种糖尿病相关酶，即葡萄糖磷酸酶（GPa）、α - 葡萄糖苷酶、蛋白酪氨酸磷酸酶1B（PTP1B）和二肽基肽酶4（DPP4）的抑制作用，评估了它们的抗糖尿病效果。化合物1 - 5和7 - 10在25.0 μM时显著刺激GLP - 1分泌，刺激率为267.5 - 433.1%，在12.5 μM时刺激率为117.8 - 348.2%。化合物1 - 4对GPa表现出显著抑制作用，IC值为18.0 - 31.3 μM；化合物1 - 5对α - 葡萄糖苷酶表现出明显抑制作用，IC值为6.9 - 18.2 μM；化合物1 - 5和10具有PTP1B抑制活性，IC值范围为35.5至80.1 μM。本研究首次揭示化合物1 - 4是有趣的GLP - 1促分泌剂以及GPa、α - 葡萄糖苷酶和PTP1B抑制剂，这为从姜科植物中寻找多靶点抗糖尿病候选药物提供了有价值的线索。
