Isospongian Diterpenoids from the Leaves of Amomum tsao‐ko Promote GLP‐1 Secretion via Ca2+/CaMKII and PKA Pathways and Inhibit DPP‐4 Enzyme

Abstract Three uncommon isospongian diterpenoids including a new one, 3‐ epi ‐kravanhin A ( 2 ), were isolated from the leaves of Amomum tsao‐ko . Compounds 2 and 3 dose‐dependently promoted GLP‐1 secretion on STC‐1 cells with promotion ratios of 109.7 % and 186.1 % (60 μM). Mechanism study demonstrated that the GLP‐1 stimulative effects of 2 and 3 were closely related with Ca 2+ /CaMKII and PKA pathways, but irrelevant to GPBAR1 and GPR119 receptors. Moreover, compound 1 showed DPP‐4 inhibitory activity with an IC 50 value of 311.0 μM. Molecular docking verified the binding affinity of 1 with DPP‐4 by hydrogen bonds between the γ ‐lactone carbonyl (C‐15) and Arg61 residue. Bioinformatics study indicated that compound 1 exerted antidiabetic effects by improving inflammation, oxidative stress and insulin resistance. This study first disclosed the presence of isospongian diterpenoids in A. tsao‐ko , which showed antidiabetic potency by promoting GLP‐1 secretion and inhibiting DPP‐4 activity.