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Article

Discovery of natural adenosine monophosphate‑activated protein kinase activators through virtual screening and activity verification studies

  • Authors:
    • Jia Hao
    • Zhen Yang
    • Jian Li
    • Lifeng Han
    • Yi Zhang
    • Tao Wang
  • View Affiliations / Copyright

    Affiliations: Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, P.R. China, Tianjin Key Laboratory of TCM Chemistry and Analysis, Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, P.R. China
  • Article Number: 203
    |
    Published online on: January 13, 2021
       https://doi.org/10.3892/mmr.2021.11842
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Abstract

The adenosine monophosphate‑activated protein kinase (AMPK) is a promising target in drug development for various metabolic diseases. In the present study, the aim was to discover natural direct AMPK activators from natural sources, thus a virtual screening for direct AMPK activators was conducted by combining ligand‑based and structure‑based screening. A common‑feature pharmacophore model (HipHop1) was generated with two hydrogen bond acceptor lipid features and one hydrophobic region feature. A total of 1,235 natural products were screened using the HipHop1 hypothesis and CDOCKER protocol successively. According to the docking score, seven hit compounds were selected for AMPK activation assays. Ultimately, (‑)‑catechin (compound 522) and licochalcone A (compound 1148) exhibited the highest AMPK activation activity. These findings may contribute to the development of AMPK activators from medicinal plants.
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1 

Gruzman A, Babai G and Sasson S: Adenosine monophosphate-activated protein kinase (AMPK) as a new target for antidiabetic drugs: A review on metabolic, pharmacological and chemical considerations. Rev Diabet Stud. 6:13–36. 2009. View Article : Google Scholar : PubMed/NCBI

2 

Daskalopoulos EP, Dufeys C, Bertrand L, Beauloye C and Horman S: AMPK in cardiac fibrosis and repair: Actions beyond metabolic regulation. J Mol Cell Cardiol. 91:188–200. 2016. View Article : Google Scholar : PubMed/NCBI

3 

Shirwany NA and Zou MH: AMPK: A cellular metabolic and redox sensor. A minireview. Front Biosci (Landmark Ed). 19:447–474. 2014. View Article : Google Scholar : PubMed/NCBI

4 

Gejjalagere Honnappa C and Mazhuvancherry Kesavan U: A concise review on advances in development of small molecule anti-inflammatory therapeutics emphasising AMPK: An emerging target. Int J Immunopathol Pharmacol. 29:562–571. 2016. View Article : Google Scholar : PubMed/NCBI

5 

Kim J, Yang G, Kim Y, Kim J and Ha J: AMPK activators: Mechanisms of action and physiological activities. Exp Mol Med. 48:e2242016. View Article : Google Scholar : PubMed/NCBI

6 

Plews RL, Mohd Yusof A, Wang C, Saji M, Zhang X, Chen CS, Ringel MD and Phay JE: A novel dual AMPK activator/mTOR inhibitor inhibits thyroid cancer cell growth. J Clin Endocrinol Metab. 100:E748–E756. 2015. View Article : Google Scholar : PubMed/NCBI

7 

Law BY, Mok SW, Chan WK, Xu SW, Wu AG, Yao XJ, Wang JR, Liu L and Wong VK: Hernandezine, a novel AMPK activator induces autophagic cell death in drug-resistant cancers. Oncotarget. 7:8090–8104. 2016. View Article : Google Scholar : PubMed/NCBI

8 

Grahame Hardie D: Regulation of AMP-activated protein kinase by natural and synthetic activators. Acta Pharm Sin B. 6:1–19. 2016. View Article : Google Scholar : PubMed/NCBI

9 

Polekhina G, Gupta A, Michell BJ, van Denderen B, Murthy S, Feil SC, Jennings IG, Campbell DJ, Witters LA, Parker MW, et al: AMPK beta subunit targets metabolic stress sensing to glycogen. Curr Biol. 13:867–871. 2003. View Article : Google Scholar : PubMed/NCBI

10 

Lefort N, St-Amand E, Morasse S, Côté CH and Marette A: The alpha-subunit of AMPK is essential for submaximal contraction-mediated glucose transport in skeletal muscle in vitro. Am J Physiol Endocrinol Metab. 295:E1447–E1454. 2008. View Article : Google Scholar : PubMed/NCBI

11 

Day P, Sharff A, Parra L, Cleasby A, Williams M, Hörer S, Nar H, Redemann N, Tickle I and Yon J: Structure of a CBS-domain pair from the regulatory gamma1 subunit of human AMPK in complex with AMP and ZMP. Acta Crystallogr D Biol Crystallogr. 63(Pt 5):587–596. 2007. View Article : Google Scholar

12 

Hardie DG, Ross FA and Hawley SA: AMPK: A nutrient and energy sensor that maintains energy homeostasis. Nat Rev Mol Cell Biol. 13:251–262. 2012. View Article : Google Scholar : PubMed/NCBI

13 

Gowans GJ, Hawley SA, Ross FA and Hardie DG: AMP is a true physiological regulator of AMP-activated protein kinase by both allosteric activation and enhancing net phosphorylation. Cell Metab. 18:556–566. 2013. View Article : Google Scholar : PubMed/NCBI

14 

Xiao B, Sanders MJ, Carmena D, Bright NJ, Haire LF, Underwood E, Patel BR, Heath RB, Walker PA, Hallen S, et al: Structural basis of AMPK regulation by small molecule activators. Nat Commun. 4:30172013. View Article : Google Scholar : PubMed/NCBI

15 

Zadra G, Photopoulos C, Tyekucheva S, Heidari P, Weng QP, Fedele G, Liu H, Scaglia N, Priolo C, Sicinska E, et al: A novel direct activator of AMPK inhibits prostate cancer growth by blocking lipogenesis. EMBO Mol Med. 6:519–538. 2014. View Article : Google Scholar : PubMed/NCBI

16 

Newman DJ and Cragg GM: Natural products as sources of new drugs over the nearly four decades from 01/1981 to 09/2019. J Nat Prod. 83:770–803. 2020. View Article : Google Scholar : PubMed/NCBI

17 

Wang T, Ruan J, Li X, Chao L, Shi P, Han L, Zhang Y and Wang T: Bioactive cyclolanstane-type saponins from the stems of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao. J Nat Med. 70:198–206. 2016. View Article : Google Scholar : PubMed/NCBI

18 

Zhang Y, Chao L, Ruan J, Zheng C, Yu H, Qu L, Han L and Wang T: Bioactive constituents from the rhizomes of Dioscorea septemloba, Thunb. Fitoterapia. 115:165–172. 2016. View Article : Google Scholar : PubMed/NCBI

19 

Zhang Y, Nakamura S, Nakashima S, Wang T, Yoshikawa M and Matsuda H: Chemical structures of constituents from the seeds of Cassia auriculata. Tetrahedron. 71:6727–6732. 2015. View Article : Google Scholar

20 

Zhang Y, Han L, Ge D, Liu X, Liu E, Wu C, Gao X and Wang T: Isolation, structural elucidation, MS profiling, and evaluation of triglyceride accumulation inhibitory effects of benzophenone C-glucosides from, leaves of mangifera indica L. J Agric Food Chem. 61:1884–1895. 2013. View Article : Google Scholar : PubMed/NCBI

21 

Lee YK, Lee WS, Hwang JT, Kwon DY, Surh YJ and Park OJ: Curcumin exerts antidifferentiation effect through AMPKalpha-PPAR-gamma in 3T3-L1 adipocytes and antiproliferatory effect through AMPKalpha-COX-2 in cancer cells. J Agric Food Chem. 57:305–310. 2009. View Article : Google Scholar : PubMed/NCBI

22 

Liu Z, Cui C, Xu P, Dang R, Cai H, Liao D, Yang M, Feng Q, Yan X and Jiang P: Curcumin activates AMPK pathway and regulates lipid metabolism in rats following prolonged clozapine exposure. Front Neurosci. 11:5582017. View Article : Google Scholar : PubMed/NCBI

23 

Price NL, Gomes AP, Ling AJ, Duarte FV, Martin-Montalvo A, North BJ, Agarwal B, Ye L, Ramadori G, Teodoro JS, et al: SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function. Cell Metab. 15:675–690. 2012. View Article : Google Scholar : PubMed/NCBI

24 

Jin Y, Liu S, Ma Q, Xiao D and Chen L: Berberine enhances the AMPK activation and autophagy and mitigates high glucose-induced apoptosis of mouse podocytes. Eur J Pharmacol. 794:106–114. 2017. View Article : Google Scholar : PubMed/NCBI

25 

Kim SG, Kim JR and Choi HC: Quercetin-induced AMP-activated protein kinase activation attenuates vasoconstriction through LKB1-AMPK signaling pathway. J Med Food. 21:146–153. 2018. View Article : Google Scholar : PubMed/NCBI

26 

Han YH, Kee JY, Park J, Kim HL, Jeong MY, Kim DS, Jeon YD, Jung Y, Youn DH, Kang J, et al: Arctigenin inhibits adipogenesis by inducing AMPK activation and reduces weight gain in high-fat diet-induced obese mice. J Cell Biochem. 117:2067–2077. 2016. View Article : Google Scholar : PubMed/NCBI

27 

Wu G, Robertson DH, Brooks CL III and Vieth M: Detailed analysis of grid-based molecular docking: A case study of CDOCKER-A CHARMm-based MD docking algorithm. J Comput Chem. 24:1549–1562. 2003. View Article : Google Scholar : PubMed/NCBI

28 

Patel Y, Gillet VJ, Bravi G and Leach AR: A comparison of the pharmacophore identification programs: Catalyst, DISCO and GASP. J Comput Aided Mol Des. 16:653–681. 2002. View Article : Google Scholar : PubMed/NCBI

29 

Zhang Y, Liu X, Han L, Gao X, Liu E and Wang T: Regulation of lipid and glucose homeostasis by mango tree leaf extract is mediated by AMPK and PI3K/AKT signaling pathways. Food Chem. 141:2896–2905. 2013. View Article : Google Scholar : PubMed/NCBI

30 

Potunuru UR, Priya KV, Varsha MKNS, Mehta N, Chandel S, Manoj N, Raman T, Ramar M, Gromiha MM and Dixit M: Amarogentin, a secoiridoid glycoside, activates AMP-activated protein kinase (AMPK) to exert beneficial vasculo-metabolic effects. Biochim Biophys Acta Gen Subj. 1863:1270–1282. 2019. View Article : Google Scholar : PubMed/NCBI

31 

Mok SWF, Zeng W, Niu Y, Coghi P, Wu Y, Sin WM, Ng SI, Gordillo-Martínez F, Gao JY, Law BYK, et al: A method for rapid screening of anilide-containing AMPK modulators based on computational docking and biological validation. Front Pharmacol. 9:7102018. View Article : Google Scholar : PubMed/NCBI

32 

Hwang JT, Park OJ, Lee YK, Sung MJ, Hur HJ, Kim MS, Ha JH and Kwon DY: Anti-tumor effect of luteolin is accompanied by AMP-activated protein kinase and nuclear factor-KB modulation in HepG2 hepatocarcinoma cells. Int J Mol Med. 28:25–31. 2011.PubMed/NCBI

33 

Bae UJ, Park J, Park IW, Chae BM, Oh MR, Jung SJ, Ryu GS, Chae SW and Park BH: Epigallocatechin-3-Gallate-rich green tea extract ameliorates fatty liver and weight gain in mice fed a high fat diet by activating the sirtuin 1 and AMP activating protein kinase pathway. Am J Chin Med. 46:617–632. 2018. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Hao J, Yang Z, Li J, Han L, Zhang Y and Wang T: Discovery of natural adenosine monophosphate‑activated protein kinase activators through virtual screening and activity verification studies. Mol Med Rep 23: 203, 2021.
APA
Hao, J., Yang, Z., Li, J., Han, L., Zhang, Y., & Wang, T. (2021). Discovery of natural adenosine monophosphate‑activated protein kinase activators through virtual screening and activity verification studies. Molecular Medicine Reports, 23, 203. https://doi.org/10.3892/mmr.2021.11842
MLA
Hao, J., Yang, Z., Li, J., Han, L., Zhang, Y., Wang, T."Discovery of natural adenosine monophosphate‑activated protein kinase activators through virtual screening and activity verification studies". Molecular Medicine Reports 23.3 (2021): 203.
Chicago
Hao, J., Yang, Z., Li, J., Han, L., Zhang, Y., Wang, T."Discovery of natural adenosine monophosphate‑activated protein kinase activators through virtual screening and activity verification studies". Molecular Medicine Reports 23, no. 3 (2021): 203. https://doi.org/10.3892/mmr.2021.11842
Copy and paste a formatted citation
x
Spandidos Publications style
Hao J, Yang Z, Li J, Han L, Zhang Y and Wang T: Discovery of natural adenosine monophosphate‑activated protein kinase activators through virtual screening and activity verification studies. Mol Med Rep 23: 203, 2021.
APA
Hao, J., Yang, Z., Li, J., Han, L., Zhang, Y., & Wang, T. (2021). Discovery of natural adenosine monophosphate‑activated protein kinase activators through virtual screening and activity verification studies. Molecular Medicine Reports, 23, 203. https://doi.org/10.3892/mmr.2021.11842
MLA
Hao, J., Yang, Z., Li, J., Han, L., Zhang, Y., Wang, T."Discovery of natural adenosine monophosphate‑activated protein kinase activators through virtual screening and activity verification studies". Molecular Medicine Reports 23.3 (2021): 203.
Chicago
Hao, J., Yang, Z., Li, J., Han, L., Zhang, Y., Wang, T."Discovery of natural adenosine monophosphate‑activated protein kinase activators through virtual screening and activity verification studies". Molecular Medicine Reports 23, no. 3 (2021): 203. https://doi.org/10.3892/mmr.2021.11842
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