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Structure related α-glucosidase inhibitory activity and molecular docking analyses of phenolic compounds from Paeonia suffruticosa

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Abstract

High postprandial hyperglycaemia is an important determinant of the development and progression of type 2 diabetes. Thus, inhibition of key digestive enzymes such as α-amylase and α-glucosidase is considered an efficient approach to control glycaemic levels in diabetics. In search of α-amylase and α-glucosidase inhibitors, the root bark of Paeonia suffruticosa was screened for inhibitors, resulting in the isolation of eleven phenolic compounds (1–11). Their enzymes inhibitory activities and inhibition mechanism were investigated using an in vitro inhibition assay and molecular docking studies. Compounds 2, 5, 6, and 8–11 (IC50 between 290 and 431 µM) inhibited α-glucosidase more effectively than the reference compound acarbose (IC50 = 1463.0 ± 29.5 µM). However, the compounds (IC50 > 800 µM) were less effective against α-amylase than acarbose (IC50 = 16.6 ± 0.9 µM). Among them, compound 10 exhibited the highest α-glucosidase inhibitory effect with an IC50 value of 290.4 ± 9.6 µM. Compounds 2, 5, 9 10 and 11 were found to be competitive inhibitors, while compounds 6 and 8 were noncompetitive inhibitors of α-glucosidase. Computational analyses showed that the main binding forces between the compounds and the main residues were hydrogen bonds. The results suggest that these compounds have the potential to be developed as α-glucosidase inhibitors.

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The NMR and MS spectra of the compounds are available as supplementary material.

References

  1. Tang X, Olatunji OJ, Zhou Y, Hou X. Allium tuberosum: Antidiabetic and hepatoprotective activities. Food Res Int 2017;102:681–9. https://doi.org/10.1016/j.foodres.2017.08.034

    Article  CAS  PubMed  Google Scholar 

  2. Organization WH Global report on diabetes: executive summary. World Health Organization; 2016. http://www.who.int/publications/i/item/9789241565257

  3. Chamberlain JJ, Kalyani RR, Leal S, Rhinehart AS, Shubrook JH, Skolnik N, et al. Treatment of type 1 diabetes: synopsis of the 2017 American diabetes association standards of medical care in diabetes. Ann Intern Med 2017;167:493–8. https://doi.org/10.7326/M17-1259

    Article  PubMed  Google Scholar 

  4. Li S. Pharmacodynamic bioequivalence testing. J Clin Pharm Ther 2012;37:497–8. https://doi.org/10.1111/j.1365-2710.2012.01338.x

    Article  CAS  PubMed  Google Scholar 

  5. Kim JG, Jo SH, Ha KS, Kim SC, Kim YC, Apostolidis E, et al. Effect of long-term supplementation of low molecular weight chitosan oligosaccharide (GO2KA1) on fasting blood glucose and HbA1c in db/db mice model and elucidation of mechanism of action. BMC Complement Alter Med 2014;14:272 https://doi.org/10.1186/1472-6882-14-272

    Article  CAS  Google Scholar 

  6. Lee KH, Ha KS, Jo SH, Lee CM, Kim YC, Chung KH, et al. Effect of long-term dietary arginyl-fructose (AF) on hyperglycemia and HbA1c in diabetic db/db mice. Int J Mol Sci 2014;15:8352–9. https://doi.org/10.3390/ijms15058352

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Ye JP. Challenges in drug discovery for thiazolidinedione substitute. Acta Pharm Sin B 2011;1:137–42. https://doi.org/10.1016/j.apsb.2011.06.011

    Article  CAS  Google Scholar 

  8. Tang D, Chen QB, Xin XL, Aisa HA. Anti-diabetic effect of three new norditerpenoid alkaloids in vitro and potential mechanism via PI3K/AKT signaling pathway. Biomed Pharmacother 2017;87:145–52. https://doi.org/10.1016/j.biopha.2016.12.058

    Article  CAS  PubMed  Google Scholar 

  9. De-Yuan H, Kai-Yu P. A revision of the Paeonia suffruticosa complex (Paeoniaceae). Nord J Bot 1999;19:289–300. https://doi.org/10.1111/j.1756-1051.1999.tb01115.x

    Article  Google Scholar 

  10. Huang Q, Chen JJ, Pan Y, He XF, Wang Y, Zhang XM, et al. Chemical profiling and antidiabetic potency of Paeonia delavayi: Comparison between different parts and constituents. J Pharm Biomed Anal 2021;198:113998 https://doi.org/10.1016/j.jpba.2021.113998

    Article  CAS  PubMed  Google Scholar 

  11. Pan Y, Gao Z, Huang XY, Chen JJ, Geng CA. Chemical and biological comparison of different parts of Maeonia suffruticosa (Mudan) based on LCMS-IT-TOF and multi-evaluation in vitro. Ind Crops Prod 2020;144:112028 https://doi.org/10.1016/j.indcrop.2019.112028

    Article  CAS  Google Scholar 

  12. Lau C, Chan C, Chan Y, Lau K, Lau T, Lam F, et al. Pharmacological investigations of the anti-diabetic effect of Cortex Moutan and its active component paeonol. Phytomedicine 2007;14:778–84. https://doi.org/10.1016/j.phymed.2007.01.007

    Article  CAS  PubMed  Google Scholar 

  13. Ryu SH, Kim SB, Yeon SW, Turk A, Jo YH, Hwang BY, et al. Phenolic constituents of Boehmeria pannosa and α-glucosidase inhibitory activity. Kor J Pharmacogn 2019;50:239–44. https://www.koreascience.or.kr/article/JAKO201905960060629.pdf

  14. Ye XP, Song CQ, Yuan P, Mao RG. α-Glucosidase and α-amylase inhibitory activity of common constituents from traditional Chinese medicine used for diabetes mellitus. Chin J Nat Med 2010;8:349–52. https://doi.org/10.1016/S1875-5364(10)60041-6

    Article  CAS  Google Scholar 

  15. Wansi JD, Lallemand MC, Chiozem DD, Toze FAA, Mbaze LMA, Naharkhan S, et al. α-Glucosidase inhibitory constituents from stem bark of Terminalia superba (Combretaceae). Phytochemistry 2007;68:2096–100. https://doi.org/10.1016/j.phytochem.2007.02.020

    Article  CAS  PubMed  Google Scholar 

  16. Abdelli I, Benariba N, Adjdir S, Fekhikher Z, Daoud I, Terki M, et al. In silico evaluation of phenolic compounds as inhibitors of α-amylase and α-glucosidase. J Biomol Struct Dyn 2021;39:816–22. https://doi.org/10.1080/07391102.2020.1718553

    Article  CAS  PubMed  Google Scholar 

  17. Nandi J, Hutcheson EL, Leadbeater NE. Combining photoredox catalysis and oxoammonium cations for the oxidation of aromatic alcohols to carboxylic acids. Tetrahedron Lett 2021;63:152632 https://doi.org/10.1016/j.tetlet.2020.152632

    Article  CAS  Google Scholar 

  18. Sang D, Yue H, Fu Y, Tian J. Cleavage of carboxylic esters by aluminum and iodine. J Org Chem 2021;86:4254–61. https://doi.org/10.1021/acs.joc.1c00034

    Article  CAS  PubMed  Google Scholar 

  19. Sun C, Zheng L, Xu W, Dushkin AV, Su W. Mechanochemical cleavage of lignin models and lignin via oxidation and a subsequent basecatalyzed strategy. Green Chem 2020;22:3489–94. https://doi.org/10.1039/D0GC00372G

    Article  CAS  Google Scholar 

  20. Lin Y, Wu X, Feng S, Jiang G, Luo J, Zhou S, et al. Five unique compounds: Xyloketals from mangrove fungus Xylaria sp. From the South China sea coast. J Org Chem 2001;66:6252–6. https://doi.org/10.1021/jo015522r

    Article  CAS  PubMed  Google Scholar 

  21. Anh HLT, Cuc NT, Tai BH, Yen PH, Nhiem NX, Thao DT, et al. Synthesis of chromonylthiazolidines and their cytotoxicity to human cancer cell lines. Molecules 2015;20:1151–60. https://doi.org/10.3390/molecules20011151

    Article  CAS  PubMed Central  Google Scholar 

  22. Ghanadian M, Sadraei H, Yousuf S, Asghari G, Choudhary MI, Jahed M. New diterpene polyester and phenolic compounds from Pycnocycla spinosa Decne. ex Boiss with relaxant effects on KCl-induced contraction in rat ileum. Phytochem Lett 2014;7:57–61. https://doi.org/10.1016/j.phytol.2013.09.016

    Article  CAS  Google Scholar 

  23. Sarkar D, Ghosh MK. Stereoselective synthesis of heliannuol G. Tetrahedron Lett 2017;58:4336–9. https://doi.org/10.1016/j.tetlet.2017.09.081

    Article  CAS  Google Scholar 

  24. Usui Tateo KH, Hayakawa I, Chinen T, Shioda S, inventor. 2016. Microtubule polymerization inhibitor. Japan patent JP2016124829. https://www.j-platpat.inpit.go.jp/c1800/PU/JP-2014-267073/1DF5432A1D913CEBC853D9129D47828F090B1DADD4308836F48D39C72CC484A5/10/en

  25. Lin J, Zhang W, Jiang N, Niu Z, Bao K, Zhang L, et al. Total synthesis of bulbophylol-B. J Nat Prod 2008;71:1938–41. https://doi.org/10.1021/np800226n

    Article  CAS  PubMed  Google Scholar 

  26. Quan YS, Zhang XY, Yin XM, Wang SH, Jin LL. Potential α-glucosidase inhibitor from Hylotelephium erythrostictum. Bioorg Med Chem Lett 2020;30:127665 https://doi.org/10.1016/j.bmcl.2020.127665

    Article  CAS  PubMed  Google Scholar 

  27. Lima TC, Ferreira AR, Silva DF, Lima EO, De Sousa DP. Antifungal activity of cinnamic acid and benzoic acid esters against Candida albicans strains. Nat Prod Res 2018;32:572–5. https://doi.org/10.1080/14786419.2017.1317776

    Article  CAS  PubMed  Google Scholar 

  28. Okutan L, Kongstad KT, Jäger AK, Staerk D. High-resolution α-amylase assay combined with high-performance liquid chromatographysolid-phase extraction-nuclear magnetic resonance spectroscopy for expedited identification of α-amylase inhibitors – proof of concept and α-amylase inhibitor in cinnamon. J Agric Food Chem 2014;62:11465–71. https://doi.org/10.1021/jf5047283

    Article  CAS  PubMed  Google Scholar 

  29. Lin YS, Chen CR, Wu WH, Wen CL, Chang CI, Hou WC. Anti-α-glucosidase and anti-dipeptidyl peptidase-IV activities of extracts and purified compounds from Vitis thunbergii var. taiwaniana. J Agr Food Chem 2015;63:6393–401. https://doi.org/10.1021/acs.jafc.5b02069

    Article  CAS  Google Scholar 

  30. Morocho V, Valle A, García J, Gilardoni G, Cartuche L, Suárez AI. α-Glucosidase inhibition and antibacterial activity of secondary metabolites from the Ecuadorian species Clinopodium taxifolium (Kunth) Govaerts. Molecules 2018;23:146 https://doi.org/10.3390/molecules23010146

    Article  CAS  PubMed Central  Google Scholar 

  31. Hu WJ, Yan L, Park D, Jeong HO, Chung HY, Yang JM, et al. Kinetic, structural and molecular docking studies on the inhibition of tyrosinase induced by arabinose. Int J Biol Macromol 2012;50:694–700. https://doi.org/10.1016/j.ijbiomac.2011.12.035

    Article  CAS  PubMed  Google Scholar 

  32. Meng Y, Su A, Yuan S, Zhao H, Tan S, Hu C, et al. Evaluation of total flavonoids, myricetin, and quercetin from Hovenia dulcis Thunb. as inhibitors of α-amylase and α-glucosidase. Plant Foods Hum Nutr 2016;71:444–9. https://doi.org/10.1007/s11130-016-0581-2

    Article  CAS  PubMed  Google Scholar 

  33. Khan KM, Qurban S, Salar U, Taha M, Hussain S, Perveen S, et al. Synthesis, in vitro α-glucosidase inhibitory activity and molecular docking studies of new thiazole derivatives. Bioorg Chem 2016;68:245–58. https://doi.org/10.1016/j.bioorg.2016.08.010

    Article  CAS  PubMed  Google Scholar 

  34. Bioinformatics and Molecular Design Research Center. Pre-ADMET program. Seoul. South Korea: Bioinformatics and Molecular Design Research Center; 2014. http://preadmet.bmdrc.org

  35. Lipinski CA. Drug-like properties and the causes of poor solubility and poor permeability. J Pharm Toxicol Methods 2000;44:235–49. https://doi.org/10.1016/S1056-8719(00)00107-6

    Article  CAS  Google Scholar 

  36. Teague SJ, Davis AM, Leeson PD, Oprea T. The design of leadlike combinatorial libraries. Angew Chem Int Ed. 1999;38:3743–8. 10.1002/(SICI)1521-3773(19991216)38:24<3743::AID-ANIE3743>3.0.CO;2-U

    Article  CAS  Google Scholar 

  37. Ghose AK, Viswanadhan VN, Wendoloski JJ. A knowledge-based approach in designing combinatorial or medicinal chemistry libraries for drug discovery. 1. A qualitative and quantitative characterization of known drug databases. J Comb Chem 1999;1:55–68. https://doi.org/10.1021/cc9800071

    Article  CAS  PubMed  Google Scholar 

  38. Oprea TI. Property distribution of drug-related chemical databases. J Comput Aided Mol Des 2000;14:251–64. https://doi.org/10.1023/A:1008130001697

    Article  CAS  PubMed  Google Scholar 

  39. Ames BN, Gurney EG, Miller JA, Bartsch H. Carcinogens as frameshift mutagens: metabolites and derivatives of 2-acetylaminofluorene and other aromatic amine carcinogens. Proc Natl Acad Sci 1972;69:3128–32. https://doi.org/10.1073/pnas.69.11.3128

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Yang J, Wang X, Zhang C, Ma L, Wei T, Zhao Y, et al. Comparative study of inhibition mechanisms of structurally different flavonoid compounds on α-glucosidase and synergistic effect with acarbose. Food Chem 2021;347:129056 https://doi.org/10.1016/j.foodchem.2021.129056

    Article  CAS  PubMed  Google Scholar 

  41. Tan Y, Chang SK, Zhang Y. Comparison of α-amylase, α-glucosidase and lipase inhibitory activity of the phenolic substances in two black legumes of different genera. Food Chem 2017;214:259–68. https://doi.org/10.1016/j.foodchem.2016.06.100

    Article  CAS  PubMed  Google Scholar 

  42. Mohan S, Eskandari R, Pinto BM. Naturally occurring sulfonium-ion glucosidase inhibitors and their derivatives: a promising class of potential antidiabetic agents. Acc Chem Res 2014;47:211–25. https://doi.org/10.1021/ar400132g

    Article  CAS  PubMed  Google Scholar 

  43. Sim L, Quezada-Calvillo R, Sterchi EE, Nichols BL, Rose DR. Human intestinal maltase-glucoamylase: Crystal structure of the Nterminal catalytic subunit and basis of inhibition and substrate specificity. J Mol Biol 2008;375:782–92. https://doi.org/10.1016/j.jmb.2007.10.069

    Article  CAS  PubMed  Google Scholar 

  44. Jones K, Sim L, Mohan S, Kumarasamy J, Liu H, Avery S, et al. Mapping the intestinal alpha-glucogenic enzyme specificities of starch digesting maltase-glucoamylase and sucrase-isomaltase. Bioorg Med Chem 2011;19:3929–34. https://doi.org/10.1016/j.bmc.2011.05.033

    Article  CAS  PubMed  Google Scholar 

  45. Zhang CC, Geng CA, Huang XY, Zhang XM, Chen JJ. Antidiabetic stilbenes from peony seeds with PTP1B, α-glucosidase, and DPPIV inhibitory activities. J Agric Food Chem 2019;67:6765–72. https://doi.org/10.1021/acs.jafc.9b01193

    Article  CAS  PubMed  Google Scholar 

  46. Zeng L, Ding H, Hu X, Zhang G, Gong D. Galangin inhibits α-glucosidase activity and formation of non-enzymatic glycation products. Food Chem 2019;271:70–9. https://doi.org/10.1016/j.foodchem.2018.07.148

    Article  CAS  PubMed  Google Scholar 

  47. Zeng L, Zhang G, Lin S, Gong D. Inhibitory mechanism of apigenin on α-glucosidase and synergy analysis of flavonoids. J Agric Food Chem 2016;64:6939–49. https://doi.org/10.1021/acs.jafc.6b02314

    Article  CAS  PubMed  Google Scholar 

  48. Proença C, Freitas M, Ribeiro D, Oliveira EF, Sousa JL, Tomé SM, et al. α-Glucosidase inhibition by flavonoids: an in vitro and in silico structure–activity relationship study. J Enzym Inhib Med Chem 2017;32:1216–28. https://doi.org/10.1080/14756366.2017.1368503

    Article  CAS  Google Scholar 

  49. Ma XL, Chen C, Yang J. Predictive model of blood-brain barrier penetration of organic compounds. Acta Pharm Sin 2005;26:500–12. https://doi.org/10.1111/j.1745-7254.2005.00068.x

    Article  CAS  Google Scholar 

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Acknowledgements

We thank Ms Lih-Mei Sheu and Ms Shu-Chi Lin, Instrumentation Centre of the College of Science, National Chung Hsing University and National Tsing Hua University for MS measurements. The nuclear magnetic resonance spectrometer (NMR) was performed in the Precision Instruments Centre of National Pingtung University of Science and Technology.

Funding

This work was supported by the Ministry of Science and Technology of Taiwan (Grants MOST 105-2320-B-020-002-MY3 and MOST 108-2320-B-020-003) and NPUST-KMU Joint Research Project (KP-109005).

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Authors and Affiliations

  1. Department of Radiation oncology, Pingtung Christian Hospital, Pingtung, 90054, Taiwan

    Po-Chun Chen

  2. Graduate Institute of Bioresources, National Pingtung University of Science and Technology, Pingtung, 91201, Taiwan

    Po-Chun Chen

  3. Department of Tropical Agriculture and International Cooperation, National Pingtung University of Science and Technology, Pingtung, 91201, Taiwan

    Bongani Sicelo Dlamini

  4. Department of Life Science, National Taitung University, Taitung, 95002, Taiwan

    Chiy-Rong Chen

  5. Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, 40402, Taiwan

    Yueh-Hsiung Kuo

  6. Department of Biotechnology, Asia University, Taichung, 41354, Taiwan

    Yueh-Hsiung Kuo

  7. Chinese Medicine Research Center, China Medical University, Taichung, 40402, Taiwan

    Yueh-Hsiung Kuo

  8. Department of Biological Science and Technology, National Pingtung University of Science and Technology, Pingtung, 91201, Taiwan

    Wen-Ling Shih & Chi-I Chang

  9. Department of Biological Science and Technology, Meiho University, Pingtung, 91201, Taiwan

    Yun-Sheng Lin

  10. Department of Pharmacology, Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan

    Chien-Hsing Lee

  11. Department of Pharmacology, School of Medicine; School of Post-Baccalaureate Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan

    Chien-Hsing Lee

  12. Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, 80708, Taiwan

    Chien-Hsing Lee

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  1. Po-Chun Chen
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Chen, PC., Dlamini, B.S., Chen, CR. et al. Structure related α-glucosidase inhibitory activity and molecular docking analyses of phenolic compounds from Paeonia suffruticosa. Med Chem Res 31, 293–306 (2022). https://doi.org/10.1007/s00044-021-02830-6

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