Cui Can, Wu Sheng-Li, Chen Ji-Jun, Gongpan Pianchou, Guan Min, Geng Chang-An
College of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, People's Republic of China.
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, People's Republic of China.
J Agric Food Chem. 2023 Nov 1;71(43):16148-16159. doi: 10.1021/acs.jafc.3c06093. Epub 2023 Oct 23.
Six new sesquiterpenoids (-), a pair of enantiomers ( and ), and six known ones (-) were isolated from the fruits of . The structures of the new compounds were elucidated by extensive spectroscopic data and ECD calculations. The stereochemistry of and was reported for the first time. All compounds showed significant GLP-1 stimulation in NCI-H716 cells with promoting ratios ranging from 90.4 to 668.9% at 50 μM. Mechanism study indicated that compound stimulated GLP-1 secretion mainly by regulating the transcription and the shearing process of proglucagon, while compound exerted its effects through up-regulating levels. Interestingly, the GLP-1 stimulative effects of and were both closely related with Ca/CaMKII and PKA pathways but irrelevant to TGR5 and GPR119 receptors. Moreover, most compounds exhibited inhibitory activity against α-glucosidase and PTP1B at concentrations of 100 and 200 μM, while showing no activity against GPa. Compounds , , , and could suppress α-glucosidase with IC values of 190.0, 204.0, 181.8, and 159.6 μM, equivalent to acarbose (IC = 212.0 μM). This study manifests that contains diverse sesquiterpenoids with multiple activities.
从[植物名称]果实中分离出6个新的倍半萜类化合物（-）、一对对映体（[对映体名称1]和[对映体名称2]）以及6个已知化合物（-）。通过广泛的光谱数据和ECD计算阐明了新化合物的结构。首次报道了[对映体名称1]和[对映体名称2]的立体化学。所有化合物在NCI-H716细胞中均表现出显著的胰高血糖素样肽-1（GLP-1）刺激作用，在50μM时促进率为90.4%至668.9%。机制研究表明，化合物[化合物名称1]主要通过调节胰高血糖素原的转录和剪切过程来刺激GLP-1分泌，而化合物[化合物名称2]通过上调[相关物质名称]水平发挥作用。有趣的是，[化合物名称1]和[化合物名称2]的GLP-1刺激作用均与Ca/CaMKII和PKA途径密切相关，但与TGR5和GPR119受体无关。此外，大多数化合物在100和200μM浓度下对α-葡萄糖苷酶和蛋白酪氨酸磷酸酶1B（PTP1B）表现出抑制活性，而对GPa无活性。化合物[化合物名称3]、[化合物名称4]、[化合物名称5]和[化合物名称6]能够抑制α-葡萄糖苷酶，IC50值分别为190.0、204.0、181.8和159.6μM，与阿卡波糖（IC50 = 212.0μM）相当。本研究表明[植物名称]含有多种具有多种活性的倍半萜类化合物。
