Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, and School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China.
Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, People's Republic of China.
Chem Biodivers. 2024 Nov;21(11):e202401407. doi: 10.1002/cbdv.202401407. Epub 2024 Sep 9.
Three uncommon isospongian diterpenoids including a new one, 3-epi-kravanhin A (2), were isolated from the leaves of Amomum tsao-ko. Compounds 2 and 3 dose-dependently promoted GLP-1 secretion on STC-1 cells with promotion ratios of 109.7 % and 186.1 % (60 μM). Mechanism study demonstrated that the GLP-1 stimulative effects of 2 and 3 were closely related with Ca/CaMKII and PKA pathways, but irrelevant to GPBAR1 and GPR119 receptors. Moreover, compound 1 showed DPP-4 inhibitory activity with an IC value of 311.0 μM. Molecular docking verified the binding affinity of 1 with DPP-4 by hydrogen bonds between the γ-lactone carbonyl (C-15) and Arg61 residue. Bioinformatics study indicated that compound 1 exerted antidiabetic effects by improving inflammation, oxidative stress and insulin resistance. This study first disclosed the presence of isospongian diterpenoids in A. tsao-ko, which showed antidiabetic potency by promoting GLP-1 secretion and inhibiting DPP-4 activity.
从草果 Amomum tsao-ko 的叶子中分离得到三种罕见的异贝壳杉二萜类化合物，包括一种新化合物 3-epi-kravanhin A（2）。化合物 2 和 3 以剂量依赖的方式促进 STC-1 细胞中 GLP-1 的分泌，促进率分别为 109.7%和 186.1%（60 μM）。机制研究表明，2 和 3 的 GLP-1 刺激作用与 Ca/CaMKII 和 PKA 途径密切相关，但与 GPBAR1 和 GPR119 受体无关。此外，化合物 1 对 DPP-4 具有抑制活性，IC 值为 311.0 μM。分子对接通过 γ-内酯羰基（C-15）和 Arg61 残基之间的氢键验证了 1 与 DPP-4 的结合亲和力。生物信息学研究表明，化合物 1 通过改善炎症、氧化应激和胰岛素抵抗发挥抗糖尿病作用。本研究首次揭示了 A. tsao-ko 中存在异贝壳杉二萜类化合物，通过促进 GLP-1 分泌和抑制 DPP-4 活性发挥抗糖尿病作用。
