Anti-Diabetic Effects and Molecular Mechanisms of Amide Alkaloids from Piper longum Based on Network Pharmacology Integrated with Cellular Assays |
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| Authors: | Guang-Hui Gou Liu Liu Sardorbek Abdubakiev Xue-Lei Xin Haji Akber Aisa Jun Li |
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| Institution: | 1. State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization and Key Laboratory of Plants Resources and Chemistry of Arid Zone, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, South Beijing Road 40-1, Urumqi 830011 Xinjiang, P. R. China
University of Chinese Academy of Sciences, Beijing, 100039 P. R. China;2. State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization and Key Laboratory of Plants Resources and Chemistry of Arid Zone, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, South Beijing Road 40-1, Urumqi 830011 Xinjiang, P. R. China |
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| Abstract: | 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 GSK3β were yielded as the top two core targets of retrofractamides A ( 1 ) and C ( 2 ). Molecular docking of compounds with AKT1 and GSK3β 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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| Keywords: | retrofractamides A and C Piper longum anti-diabetic network pharmacology molecular docking |
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