Xue Gui-Min, Zhao Chen-Guang, Xue Jin-Feng, Duan Jiang-Jing, Pan Hao, Jia Yao-Yao, Du Kun, Zhi Yan-Le, Feng Wei-Sheng
College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, China.
College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, China.
Fitoterapia. 2023 Apr;166:105472. doi: 10.1016/j.fitote.2023.105472. Epub 2023 Mar 11.
Three new monomeric (1-3) and two newdimeric guaianolides (4 and 5), along with three known analogues (6-8) were isolated from the aerial part of Achillea alpina L. Compounds 1-3 were three novel 1,10-seco-guaianolides, while 4 and 5 were two novel 1,10-seco-guaianolides involved heterodimeric [4 + 2] adducts. The new structures were elucidated by analysis of spectroscopic data and quantum chemical calculations. All isolates were evaluated for their hypoglycemic activity with a glucose consumption model in palmitic acid (PA)-induced HepG2-insulin resistance (IR) cells, and compound 1 showed the most promising activity. A mechanistic study revealed that compound 1 appeared to mediate hypoglycemic activity via inhibition of the ROS/TXNIP/NLRP3/caspase-1 pathway.
从高山蓍草的地上部分分离出三种新的单体（1-3）和两种新的二聚愈创木内酯（4和5），以及三种已知类似物（6-8）。化合物1-3是三种新型的1,10-断愈创木内酯，而4和5是两种新型的涉及[4 + 2]异二聚体加合物的1,10-断愈创木内酯。通过光谱数据分析和量子化学计算阐明了新结构。在棕榈酸（PA）诱导的HepG2胰岛素抵抗（IR）细胞中，利用葡萄糖消耗模型对所有分离物的降血糖活性进行了评估，化合物1表现出最有前景的活性。机理研究表明，化合物1似乎通过抑制ROS/TXNIP/NLRP3/半胱天冬酶-1途径介导降血糖活性。
