Ponce-Zea, Jorge-Eduardo Ryu, Byeol Lee, Ju-Yong Park, Eun-Jin Mai, Van-Hieu Doan, Thi-Phuong Lee, Hee-Ju Oh, Won-Keun 2024-10-04T00:30:10Z 2024-10-04T00:30:10Z 2024-10-02 2024-09 https://pubs.kist.re.kr/handle/201004/150698 As part of our ongoing research on new anti-diabetic compounds from ethnopharmacologically consumed plants, two previously undescribed lupane-type triterpenoids (1 and 2) with dicarboxylic groups, an undescribed nor-taraxastane-type triterpenoid (3), and 14 known compounds (4-17) were isolated from the leaves of Cleistocalyx operculatus. Extensive spectroscopic analysis (IR, HRESIMS, 1D, and 2D NMR) was used for structure elucidation, while the known compounds were compared to reference data reported in the scientific literature. All the isolates (1-17) were evaluated for their inhibitory effects on the protein tyrosine phosphatase 1B (PTP1B) enzyme. Compounds 6, 9, and 17 showed strong PTP1B inhibitory activities. The mechanism of PTP1B inhibition was studied through enzyme kinetic experiments. A non-competitive mechanism of inhibition was determined using Lineweaver-Burk plots for compounds 6, 9, and 17. Additionally, Dixon plots were employed to determine the inhibition constant. Further insights were gained through a structure-activity relationship study and molecular docking analysis of isolated compounds with the PTP1B crystal structure. Moreover, all isolates (1-17) were tested for their stimulatory effects on the uptake of 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl) amino]-D-glucose (2-NBDG) in differentiated 3T3-L1 adipocyte cells. Compounds 6, 13, and 17 exhibited strong glucose absorption stimulation activity in a dose-dependent manner. English Multidisciplinary Digital Publishing Institute (MDPI) In Vitro and In Silico Analysis of PTP1B Inhibitors from Cleistocalyx operculatus Leaves and Their Effect on Glucose Uptake Article 10.3390/nu16172839 1 Nutrients, v.16, no.17 Nutrients 16 17 Y scie scopus 001312831700001 2-s2.0-85203710304 Nutrition & Dietetics Nutrition & Dietetics Article TYROSINE-PHOSPHATASE 1B OLEANOLIC ACID TARGET TRITERPENOIDS TRANSLOCATION CONSTITUENTS DERIVATIVES FLAVONOIDS Cleistocalyx operculatus Myrtaceae protein tyrosine phosphatase 1B (PTP1B) kinetic molecular docking glucose uptake