Diarylheptanoid-chalcone hybrids with PTP1B and α-glucosidase dual inhibition from Alpinia katsumadai.

• 16 New diarylheptanoid-chalcone hybrids were isolated from A. katsumadai. • Compounds 1 – 3 , 5 – 7 , 11 – 14 , 21 – 25 , and 27 showed PTP1B selective inhibition. • All compounds showed obvious inhibition on α -glucosidase. • Compounds 1 , 3 , and 12 were α -glucosidase and PTP1B mixed-type inhibitors. The EtOH extracts of the dried seeds of Alpinia katsumadai were revealed with hypoglycemic effects on db/db mice at the concentration of 200 mg/kg. In order to clarify the antidiabetic constituents, 16 new diarylheptanoid-chalcone hybrids, katsumadainols A 1 −A 16 (1 – 16), together with 13 known analogues (17 – 29), were isolated from A. katsumadai under the guidance of bioassay. Most of the compounds showed α -glucosidase and PTP1B dual inhibition, among which compounds 1 – 3 , 5 – 7 , 11 – 14 , 21 – 25 , and 27 showed PTP1B/TCPTP selective inhibition with IC 50 values ranging from 22.0 to 96.7 μM, which were 2–10 times more active than sodium orthovanadate (IC 50 , 215.7 μM). All compounds exhibited obvious inhibition against α -glucosidase with IC 50 values of 2.9–29.5 μM, indicating 6–59 times more active than acarbose (IC 50 , 170.9 μM). Study of enzyme kinetics indicated compounds 1 , 3 , and 12 were PTP1B and α -glucosidase mixed-type inhibitors with K i values of 13.1, 12.9, 21.6 μM, and 4.9, 7.4, 3.4 μM, respectively. [ABSTRACT FROM AUTHOR]