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

• Published in: Chemistry & biodiversity 2024-11, Vol.21 (11), p.e202401407-n/a
• Main Authors: Wang, Yun, Wu, Sheng‐Li, Li, Xin‐Yu, Gongpan, Pianchou, Fu, Hang, Liao, Xiang‐Ming, Yang, Yi, Huang, Mei, Huang, Xiao‐Yan, Ma, Yun‐Bao, Li, Da‐Hong, Geng, Chang‐An
• Format: Article
• Language: English
• Subjects: Amomum; Amomum tsao-ko; Bioinformatics; Biological activity; Ca2+/calmodulin-dependent protein kinase II; Calcium ions; Carbonyl compounds; Carbonyls; Chemical bonds; Diabetes mellitus; Diterpenes; GLP-1 secretion; Hydrogen bonding; Hydrogen bonds; Insulin resistance; Isospongian diterpenoids; Molecular docking; Oxidation resistance; Oxidative stress; Protein kinase A; Secretion; Terpenoids
• ISSN: 1612-1872; 1612-1880; 1612-1880
• DOI: 10.1002/cbdv.202401407

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 Ca2+/CaMKII and PKA pathways, but irrelevant to GPBAR1 and GPR119 receptors. Moreover, compound 1 showed DPP‐4 inhibitory activity with an IC50 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.