Antidiabetic effects of two naphthoquinones from the branches and leaves of Tectona grandis and possible mechanism.

Tectona grandis is a Dai medicine that plays an important role in traditional medicine in India, Myanmar, West Africa, and Yunnan Province in China. T. grandis was recorded as an anti-diabetic herb in the Ayurvedic Pharmacopoeia; however, its potential antidiabetic components and possible mechanisms of action have almostly not been described to far. To completely comprehend the pharmacological components and therapeutic potential of T. grandis, we isolated chemical components from the plant's leaves and branches, evaluated their antidiabetic activities, and explored the possible mechanisms of active compounds using molecular docking and network pharmacology. In this study, two new quinones (1-2) and eighteen known compounds (3-20) were isolated and identified from T. grandis. Except for the new quinones 1 and 2, compounds 4, 11-12, 14-15, 18-20 were separated from T. grandis for the first time. The naphthoquinones 1 and 3 showed significant antidiabetic activities in α-glucosidase inhibition assay (IC₅₀: 92.52 ± 5.05 and 45.37 ± 1.50 μM, respectively), glucose uptake assay (Inhibition rate: 63.90 ± 1.04 % and 65.41 ± 1.96 %, respectively) and preadipocyte differentiation inhibition assay (Lipid droplet content decreased by 8.49 ± 0.71 % and 13.89 ± 0.29 %, respectively, compared to the model group). Our study also revealed that T. grandis might treat diabetes by targeting CASP3, ESR1, and PTGS2. This study provided important support for the traditional usage of T. grandis as an antidiabetic herb by identifying its antidiabetic components and possible mechanism.