Discovery of bicyclic polyprenylated acylphloroglucinols from Hypericum himalaicum with glucose transporter 4 translocation activity

• Published in: Bioorganic chemistry Vol. 129; p. 106160
• Main Authors: Cheng, Haitao, Yao, Yanhong, Chen, Huijian, Zhao, Ping, Kang, Xinyi, Zhou, Xiuteng, Liu, Wenqi, Yang, Xinzhou
• Format: Journal Article
• Language: English
• Published: SAN DIEGO Elsevier Inc 01.12.2022; Elsevier
• Subjects: Biochemistry & Molecular Biology; BPAPs; Chemistry; Chemistry, Organic; Circular Dichroism; ECD calculation; Glucose Transport Proteins, Facilitative; GLUT-4; Hyperhimatins A-P; Hypericum - chemistry; Hypericum himalaicum; Life Sciences & Biomedicine; Magnetic Resonance Spectroscopy; Molecular Structure; Phloroglucinol - chemistry; Phloroglucinol - pharmacology; Physical Sciences; Science & Technology; Hypericum himalaicum; BPAPs; ECD calculation; Hyperhimatins A-P; GLUT-4; PHLOROGLUCINOL DERIVATIVES; CIRCULAR-DICHROISM
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2022.106160

[Display omitted] •Sixteen novel bicyclic polyprenylated acylphloroglucinols were isolated from Hypericum himalaicum.•All compounds were assessed for the glucose transporter 4 (GLUT-4) translocation.•Compound 10 exhibited outstanding GLUT-4 translocation effect to L6 cells. Hyperhimatins A-P (1–16), sixteen new bicyclic polyprenylated acylphloroglucinols (BPAPs), were isolated and identified from Hypericum himalaicum. The planner structures of hyperhimatins A-P were confirmed via extensive NMR and careful HRESIMS data analysis. The absolute configurations of the new compounds were mainly determined by electronic circular dichroism (ECD) calculation, NMR calculation, and the circular dichroism data of the in situ formed [Rh2(OCOCF3)4] complexes. All compounds were assessed for the glucose transporter 4 (GLUT-4) translocation and expression enhancing effects in L6 myotubes. Compounds 1–16 could promote the GLUT-4 expression by the range of 1.95–6.04 folds, and accelerate the GLUT-4 fusion with the plasma membrane ranged from 53.56% to 76.97% at a consistence of 30 μg/mL, among compound 10 displayed the strongest GLUT-4 translocation effect.