Hypoglycemic effects of lanostane triterpenoids from the fruiting bodies of Ganoderma lingzhi.

The macrofungus Ganoderma is renown as a medicinal and edible mushroom in Asian countries for its potential to enhance vitality and promote longevity. Five previously undescribed lanostane triterpenoids, ganoderenic acids J-N (1-5), together with 42 known ones (6-47), were isolated from the fruiting bodies of Ganoderma lingzhi. The structures of the new compounds were elucidated through comprehensive spectroscopic analyses, NMR chemical shifts and electronic circular dichroism (ECD) calculations. Among them, compound 7 acted as a noncompetitive inhibitor against protein tyrosine phosphatase 1B (PTP1B) with IC50 value of 5.95 ± 0.41 μM. Moreover, compounds 7, 11, 14-17, and 22 exhibited promising inhibitory activity against α-glucosidase with IC50 values ranging from 32.72 to 146.10 μM, compared with that of acarbose. The dual-target inhibitory mechanisms of compound 7 against PTP1B and α-glucosidase were illuminated by the enzyme kinetic studies, molecular docking, and dynamic simulations. Consistently, compound 7 could significantly reduce postprandial blood glucose (PBG) levels in normal mice during glucose/sucrose/maltose tolerance test.