Diterpenoids from the leaves of Thuja orientalis L. and their inhibitory effects on PTP1B and α-glucosidase.

Abstract

A phytochemical investigation of the leaves of Thuja orientalis L. resulted in the isolation and identification of 29 diterpenoids, including labdane, pimarane, and abietane derivatives. Among these, the new diterpenoid thujaorienin A (20) were characterized and eight labdane-type diterpenoids (15-16, 21-25 and 28) were reported for the first time from this species. This study provides a comprehensive diterpenoid profile of T. orientalis leaves. All isolated compounds were evaluated for protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase inhibitory activities. Compounds 11 and 28 exhibited the most potent PTP1B inhibitory activity, with IC50 values of 12.3 ± 0.2 and 12.6 ± 1.0 μM, respectively. In addition, compounds 11 and 28 showed significant α-glucosidase inhibitory activity, with IC50 values of 9.2 ± 0.3 μM and 34.5 ± 5.5 μM, respectively. Enzyme kinetic analyses elucidated their inhibition mechanisms, and molecular docking studies supported the observed enzyme-ligand interactions. In cell-based assays, compound 11 exhibited no significant cytotoxicity and effectively inhibited intracellular PTP1B activity, resulting in enhanced phosphorylation of insulin receptor β (IRβ), insulin receptor substrate 1 (IRS1), and protein kinase B (AKT), as well as increased glucose uptake. These findings suggest that compound 11 from T. orientalis may serve as candidates for further investigation for their potential antidiabetic effects through PTP1B inhibition.