DOI QR코드

DOI QR Code

Inhibitory Activity of 4-O-Benzoyl-3'-O-(O-Methylsinapoyl)Sucrose from Polygala tenuifolia on Escherichia coli β-Glucuronidase

  • Kim, Jang Hoon (Department of Herbal Crop Research, National Institute of Horticultural and Herbal Science, RDA) ;
  • Vinh, Le Ba (Institute of Marine Biochemistry(IMBC), Vietnam Academy of Science and Technology(VAST)) ;
  • Hur, Mok (Department of Herbal Crop Research, National Institute of Horticultural and Herbal Science, RDA) ;
  • Koo, Sung-Cheol (Department of Herbal Crop Research, National Institute of Horticultural and Herbal Science, RDA) ;
  • Park, Woo Tae (Department of Herbal Crop Research, National Institute of Horticultural and Herbal Science, RDA) ;
  • Moon, Youn-Ho (Department of Herbal Crop Research, National Institute of Horticultural and Herbal Science, RDA) ;
  • Lee, Yoon Jeong (Department of Herbal Crop Research, National Institute of Horticultural and Herbal Science, RDA) ;
  • Kim, Young Ho (College of Pharmacy, Chungnam National University) ;
  • Huh, Yun-Chan (Department of Herbal Crop Research, National Institute of Horticultural and Herbal Science, RDA) ;
  • Yang, Seo Young (Department of Pharmaceutical Engineering, Sangji University)
  • 투고 : 2021.08.06
  • 심사 : 2021.09.08
  • 발행 : 2021.11.28

초록

Bacterial β-glucuronidase in the intestine is involved in the conversion of 7-ethyl-10-hydroxycamptochecin glucuronide (derived from irinotecan) to 7-ethyl-10-hydroxycamptothecin, which causes intestinal bleeding and diarrhea (side effects of anti-cancer drugs). Twelve compounds (1-12) from Polygala tenuifolia were evaluated in terms of β-glucuronidase inhibition in vitro. 4-O-Benzoyl-3'-O-(O-methylsinapoyl) sucrose (C3) was highly inhibitory at low concentrations. C3 (an uncompetitive inhibitor) exhibited a ki value of 13.4 μM; inhibitory activity increased as the substrate concentration rose. Molecular simulation revealed that C3 bound principally to the Gln158-Tyr160 enzyme loop. Thus, C3 will serve as a lead compound for development of new β-glucuronidase inhibitors.

키워드

과제정보

This work was supported by the basic research project(PJ012559012021) of National Institute of Horticultural and Herbal Science, RDA.

참고문헌

  1. Dashnyam P, Mudududdla R, Hsieh T-J, Lin T-C, Lin H-Y, Chen P-Y, et al. 2018. β-Glucuronidases of opportunistic bacteria are the major contributors to xenobiotic-induced toxicity in the gut. Sci. Rep. 8: 16372. https://doi.org/10.1038/s41598-018-34678-z
  2. Awolade P, Cele N, Kerru N, Gummidi L, Oluwakemi E. 2020. Therapeutic significance of β-glucuronidase activity and its inhibitors: A review. Eur. J. Med. Chem. 187: 111921. https://doi.org/10.1016/j.ejmech.2019.111921
  3. Sun C-P, Yan J-K, Yi J, Zhang XY, Yu Z-L, Huo X-K, et al. 2020. The study of inhibitory effect of natural flavonoids toward β-glucuronidase and interaction of flavonoids with β-glucuronidase. Inter. J. Biol. Macromol. 143: 349-358. https://doi.org/10.1016/j.ijbiomac.2019.12.057
  4. Wallace BD, Wang H, Lane KT, Scott JE, Orans J, Koo JS, et al. 2005. Alleviating cancer drug toxicity by inhibiting a bacterial enzyme. Science 330: 831-835. https://doi.org/10.1126/science.1191175
  5. Weng Z-M, Wang P, Ge G-B, Dai Z-R, Wu D-C, Zou L-W, et al. 2017. Structure-activity relationships of flavonoids as natural inhibitors against E. coli β-glucuronidase. Food Chem. Toxicol. 109: 975-983. https://doi.org/10.1016/j.fct.2017.03.042
  6. Smith NF, Figg WD, Sparreboom A. 2006. Pharmacogenetics of irinotecan metabolism and transport: an update. Toxicol. In Vitro 20: 163-175. https://doi.org/10.1016/j.tiv.2005.06.045
  7. Cheng KW, Tseng CH, Yang CN, Tzeng CC, Cheng TC, Leu YL, et al. 2017. Specific inhibition of bacterial β-glucuronidase by pyrazolo[4,3-c]quinoline derivatives via a pH-dependent manner to suppress chemotherapy-induced intestinal toxicity. J. Med. Chem. 60: 9222-9238. https://doi.org/10.1021/acs.jmedchem.7b00963
  8. Wei B, Yang W, Yan Z-X, Zhang Q-W, Yan R. 2018. Prenylflavonoids sanggenon C and kuwanon g from mulberry (Morus alba L.) as potent broad-spectrum bacterial β-glucuronidase inhibitors: Biological evaluation and molecular docking studies. J. Funct. Foods 48: 210-219. https://doi.org/10.1016/j.jff.2018.07.013
  9. Lacaille-Dubois M-A, Delaude C, Mitaine-Offer A-C. 2020. A review on the phytopharmacological studies of the genus Polygala. J. Ethnopharm. 249: 112417. https://doi.org/10.1016/j.jep.2019.112417
  10. Li J, Zhong J, Chen H, Yu Q, Yan C. 2020. Structural characterization and anti-neuroinflammatory activity of a heteropolysaccharide isolated from the rhizomes of Polygala tenuifolia. Ind. Crops Prod. 155: 112792. https://doi.org/10.1016/j.indcrop.2020.112792
  11. Zhang F-S, Zhang X, Wang Q-Y, Pu Y-J, Du C-H, Qin X-M, et al. 2020. Cloning, yeast expression, and characterization of a β-amyrin C-28 oxidase (CYP716A249) involved in triterpenoid biosynthesis in Polygala tenuifolia. Biol. Pharm. Bull. 43: 1839-1846. https://doi.org/10.1248/bpb.b20-00343
  12. Dong X-z, Huang C-I, Yu B-y, Hu Y, Mu L-h, Liu P. 2014. Effect of tenuifoliside A isolated from Polygala tenuifolia on the ERK and PI3K pathways in C6 glioma cells. Phytomedicine 21: 1178-1188. https://doi.org/10.1016/j.phymed.2014.04.022
  13. Liu J, Liu A, Mao F, Zhao Y, Cao Z, Cen N, et al. 2019. Determination of the active ingredients and biopotency in Polygala tenuifolia Willd. and the ecological factors that influence them. Ind. Crops Prod. 134: 113-123. https://doi.org/10.1016/j.indcrop.2019.03.074
  14. Kim K-S, Lee D-S, Bae G-S, Park S-J, Kang D-G, Lee H-S, et al. 2013. The inhibition of JNK MAPK and NF-κB signaling by tenuifoliside A isolated from Polygala tenuifolia in lipopolysaccharide-induced macrophages is associated with its anti-inflammatory effect. Eur. J. Pharmacol. 721: 267-276. https://doi.org/10.1016/j.ejphar.2013.09.026
  15. Taha M, Ullah H, Muqarrabun LMRA, Khan MN, Rahim F, Ahmat N, et al. 2018. Synthesis of bis-indolylmethanes as new potential inhibitors of β-glucuronidase and their molecular docking studies. Eur. J. Med. Chem. 143: 1757-1767. https://doi.org/10.1016/j.ejmech.2017.10.071
  16. Vinh LB, Kim JH, Lee JS, Nguyet NTM, Yang SY, Ma JY, et al. 2018. Soluble epoxide hydrolase inhibitory activity of phenolic glycosides from Polygala tenuifolia and in silico approach. Med. Chem. Res. 27: 726-734. https://doi.org/10.1007/s00044-017-2096-2
  17. Vinh LB, Heo M, Phong NV, Ali I, Koh YS, Kim YH, et al. 2020. Bioactive compounds from Polygala tenuifolia and their inhibitory effects on lipopolysaccharide-stimulated pro-inflammatory cytokine production in bone marrow-derived dendritic cells. Plants 9: 1240. https://doi.org/10.3390/plants9091240
  18. Liew SY, Sivasothy Y, Shaikh NN, Isa DM, Lee VS, Choudhary MI, et al. 2020. β-Glucuronidase inhibitors from Malaysian plants. J. Med. Struct. 1221: 128743. https://doi.org/10.1016/j.molstruc.2020.128743
  19. Chen G-Y, Zhang H, Yang F-Q. 2021. A simple and portable method for β-glucosidase activity assay and its inhibitor screening based on a personal glucose meter. Anal. Chim. Acta 1142: 19-27. https://doi.org/10.1016/j.aca.2020.10.047
  20. Khan KM, Saad SM, Shaikh NN, Hussain S, Fakhri MI, Perveen S, et al. 2014. Synthesis and β-glucuronidase inhibitory activity of 2-arylquinazolin-4(3H)-ones. Bioorg. Med. Chem. 22: 3449-3454. https://doi.org/10.1016/j.bmc.2014.04.039
  21. Taha M, Almandil NB, Rashid U, Ali M, Ibrahim M, Gollapalli M, et al. 2019. 2,5-Disubstituted thiadiazoles as potent β-glucuronidase inhibitors; Synthesis, in vitro and in silico studies. Bioorg. Chem. 91: 103126. https://doi.org/10.1016/j.bioorg.2019.103126
  22. Cheng K-W, Tseng C-H, Tzeng C-C, Leu Y-L, Cheng T-C, Wang J-Y, et al. 2019. Pharmacological inhibition of bacterial β-glucuronidase prevents irinotecan-induced diarrhea without impairing its antitumor efficacy in vivo. Pharmacol. Res. 139: 41-49. https://doi.org/10.1016/j.phrs.2018.10.029
  23. Yang W, Wei B, Yan R. 2018. Amoxapine demonstrates incomplete inhibition of β-glucuronidase activity from human gut microbiota. SLAS Discov. 23: 76-83. https://doi.org/10.1177/2472555217725264
  24. Ebuzoeme C, Etim I, Ikimi A, Song J, Du T, Hu M, et al. 2021. Glucuronides hydrolysis by intestinal microbial β-glucuronidases (GUS) is affected by sampling, enzyme preparation, buffer pH, and species. Pharmaceutics 13: 1043. https://doi.org/10.3390/pharmaceutics13071043