New α‑Glucosidase Inhibitors from the Whole Plant of Hypericum beanii Based on Ligand Fishing and Molecular Networking Analysis

• Published in: Journal of agricultural and food chemistry 2024-05, Vol.72 (20), p.11452-11464
• Main Authors: Hu, Rui-Dan, Lin, Wei-Yao, Feng, Qian, Liu, Jinru, Chen, Yidi, Ji, Aijia, Wang, Caiyan, Cao, Liping, Zhang, Rong, Liu, Zhongqiu, Cui, Hui, Liang, Qi, Zhang, Rong-Rong
• Format: Article
• Language: English
• Subjects: alpha-Glucosidases - chemistry; alpha-Glucosidases - metabolism; Bioactive Constituents, Metabolites, and Functions; Glycoside Hydrolase Inhibitors - chemistry; Glycoside Hydrolase Inhibitors - pharmacology; Hypericum - chemistry; Kinetics; Ligands; Molecular Docking Simulation; Molecular Structure; Plant Extracts - chemistry; Plant Extracts - pharmacology; Structure-Activity Relationship
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/acs.jafc.4c00500

In this work, a new rapid and targeted method for screening α-glucosidase inhibitors from Hypericum beanii was developed and verified. Ten new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperlagarol A–J (1–10), and nine known PPAPs (11–19) were obtained from H. beanii. Their structures were identified by using comprehensive analyses involving mass spectrometry, ultraviolet spectroscopy, infrared spectroscopy, nuclear magnetic resonance spectroscopy, and electron capture dissociation calculations. 1 and 2 are two new rare 2,3-seco-spirocyclic PPAPs, 3 and 4 are two novel 12,13-seco-spirocyclic PPAPs, 5 and 6 are two novel spirocyclic PPAPs, 7 and 8 are two new unusual spirocyclic PPAPs with complex bridged ring systems, and 9 and 10 are two novel nonspirocyclic PPAPs. α-GC inhibitory activities of all isolated compounds were tested. Most of them displayed inhibitory activities against α-glucosidase, with the IC50 values ranging from 6.85 ± 0.65 to 112.5 ± 9.03 μM. Moreover, the inhibitory type and mechanism of the active compounds were further analyzed using kinetic studies and molecular docking.