Lanostane Triterpenoids with PTP1B Inhibitory and Glucose-Uptake Stimulatory Activities from Mushroom Fomitopsis pinicola Collected in North America.

A chemical investigation on the fruiting bodies of Fomitopsis pinicola led to the isolation and identification of 28 lanostane triterpenoids including 11 new compounds (1-11) and 17 known analogues (12-28). Their structures were elucidated by extensive one-dimensional NMR, two-dimensional NMR, and MS spectra. All isolates were tested for their anti-inflammatory activity, protein tyrosine phosphatase 1B (PTP1B) inhibitory activity in vitro, and effect on glucose uptake in insulin-resistant HepG2 cells. Compounds 1, 4, 22, 23, and 27 inhibited the nitric oxide released from the LPS-induced RAW 264.7 cell assay with IC50 values in the range of 21.4-27.2 μM. Compounds 18, 22, 23, and 28 showed strong PTP1B inhibitory activity with IC50 values in the range of 20.5-29.9 μM, comparable to that of the positive control of oleanolic acid (15.0 μM). Compounds 18 and 22 were confirmed to be good competitive inhibitors of PTP1B by kinetic analysis. In addition, compounds 18, 22, and 28 were found to stimulate glucose uptake in the insulin-resistant HepG2 cells in the dose from 6.25 to 100 μM. These findings indicated the potential of F. pinicola in the development of functional food or medicine for the prevention and treatment of diabetes.