Journal
CHEMISTRY & BIODIVERSITY
Volume 20, Issue 1, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbdv.202200904
Keywords
retrofractamides A and C; Piper longum; anti-diabetic; network pharmacology; molecular docking
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This study discovered that retrofractamides A and C from Piper longum have anti-diabetic activity by activating the PI3K/AKT pathway. These compounds promote glucose consumption, uptake, glycogen synthesis, and glycolysis.
Piper longum is a well-known spice and traditional medicine. It was revealed to possess anti-diabetic activity, but few information about its active component and underlying mechanism could be available. In this study, retrofractamides A (1) and C (2) isolated from P. longum showed potent inhibitory activity against PTP1B. Therefore, the potential mechanism was predicted by network pharmacology and molecular docking. PI3K/AKT was obtained as the most remarkable pathway against type 2 diabetes mellitus (T2DM), and AKT1 and GSK3 beta were yielded as the top two core targets of retrofractamides A (1) and C (2). Molecular docking of compounds with AKT1 and GSK3 beta showed strong binding affinity between them. Additionally, cellular experiments with a L6 cell model was conducted to further verify the above predictions. Results indicated that retrofractamides A (1) and C (2) exerted anti-diabetic effect via activating PI3K/AKT pathway, and they promoted glucose consumption, glucose uptake, glycogen synthesis and glycolysis.
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