Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
권호 표지
DOI QR코드

DOI QR Code

Inhibition of the Calcineurin Pathway by Two Tannins, Chebulagic Acid and Chebulanin, Isolated from Harrisonia abyssinica Oliv.

  • Lee, Won Jeong (Division of Biosystems Research, Korea Research Institute of Bioscience and Biotechnology) ;
  • Moon, Jae Sun (Division of Biosystems Research, Korea Research Institute of Bioscience and Biotechnology) ;
  • Kim, Sung In (Division of Biosystems Research, Korea Research Institute of Bioscience and Biotechnology) ;
  • Kim, Young Tae (Division of Biosystems Research, Korea Research Institute of Bioscience and Biotechnology) ;
  • Nash, Oyekanmi (Southwest Biotechnology Center of Excellence, Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan) ;
  • Bahn, Yong-Sun (Department of Biotechnology, Yonsei University) ;
  • Kim, Sung Uk (Division of Biosystems Research, Korea Research Institute of Bioscience and Biotechnology)
  • Received : 2014.05.14
  • Accepted : 2014.07.07
  • Published : 2014.10.28
Download PDF
⟨ Previous Next ⟩

Abstract

In order to discover and develop novel signaling inhibitors from plants, a screening system was established targeting the two-component system of Cryptococcus neoformans by using the wild type and a calcineurin mutant of C. neoformans, based on the counter-regulatory action of high-osmolarity glycerol (Hog1) mitogen-activated protein kinase and the calcineurin pathways in C. neoformans. Among 10,000 plant extracts, that from Harrisonia abyssinica Oliv. exhibited the most potent inhibitory activity against C. neoformans var. grubii H99 with fludioxonil. Bioassay-guided fractionation was used to isolate two bioactive compounds from H. abyssinica, and these compounds were identified as chebulagic acid and chebulanin using spectroscopic methods. These compounds specifically inhibited the calcineurin pathway in C. neoformans. Moreover, they exhibited potent antifungal activities against various human pathogenic fungi with minimum inhibitory concentrations ranging from 0.25 to over $64{\mu}g/ml$.

Keywords

References

  1. Baldé AM, Pieters L, Bruyne TD, Geerts S, Berghe DV, Vlietinck A. 1995. Biological investigations on Harrisonia abyssinica. Phytomedicine 4: 299-302.
  2. Balde AM, Pieters L, Apers S, Bruyne TD, Heuvel HVD, Claeys M, Vlietinck A. 1999. Oumarone, bissaone, and aissatone, unusual prenylated polyketides from Harrisonia abyssinica. J. Nat. Prod. 62: 364-366. https://doi.org/10.1021/np980379r
  3. Balde AM, Vanhaelen M, Daloze D. 1988. 5-Dehydrooriciopsin, a ring-D cleaved tetranortriterpenoid from Harrisonia abyssinica. Phytochemistry 27: 942-943. https://doi.org/10.1016/0031-9422(88)84129-3
  4. Clinical and Laboratory Standards Institute. 2008. Reference Methods for Broth Dilution Antifungal Susceptibility Testing of Yeasts, pp. 1-20. 3rd Ed. CLSI document M27-A3. Clinical and Laboratory Standards Institute, Pennsylvania.
  5. De Llanos R, Hernandez-Haro C, Barrio E, Querol A, Fernandez-Espinar MT, Molina M. 2010. Differences in activation of MAP kinase and variability in the polyglutamine tract of Slt2 in clinical and non-clinical isolates of Saccharomyces cerevisiae. Yeast 27: 549-561. https://doi.org/10.1002/yea.1799
  6. Finn RK. 1959. Theory of agar diffusion methods for bioassay. Anal. Chem. 31: 975-977. https://doi.org/10.1021/ac60150a040
  7. Gao H, Huang YN, Xu PY, Kawabata J. 2007. Inhibitory effect on $\alpha$-glucosidase by the fruits of Terminalia chebula Retz. Food Chem. 105: 628-634. https://doi.org/10.1016/j.foodchem.2007.04.023
  8. Goldstein AL. 2001. Development of Saccharomyces cerevisiae as a model pathogen: a system for the genetic identification of gene products required for survival in the mammalian host environment. Genetics 159: 499-513.
  9. Idnurm A, Bahn YS, Nielsen K, Lin X, Fraser JA, Heitman J. 2005. Deciphering the model pathogenic fungus Cryptococcus neoformans. Nat. Rev. Microbiol. 3: 753-764. https://doi.org/10.1038/nrmicro1245
  10. Jabra-Rizk MA, Falkler WA, Enwonwu CO, Onwujekwe DI, Merz G, Meiller TF. 2001. Prevalence of yeast among children in Nigeria and the United States. Oral Microbiol. Immunol. 16: 383-385. https://doi.org/10.1034/j.1399-302X.2001.160611.x
  11. Kojima K, Bahn YS, Heitman J. 2006. Calcineurin, Mpk1 and Hog1 MAPK pathways independently control fludioxonil antifungal sensitivity in Cryptococcus neoformans. Microbiology 152: 591-604. https://doi.org/10.1099/mic.0.28571-0
  12. Kozubowski L, Lee SC, Heitman J. 2008. Signalling pathways in the pathogenesis of Cryptococcus. Cell. Microbiol. 11: 370-380.
  13. Mayaka RK, Langat MK, Omolo JO, Cheplogoi PK. 2012. Antimicrobial prenylated acetophenones from berries of Harrisonia abyssinica. Planta Med. 78: 383-386. https://doi.org/10.1055/s-0031-1298143
  14. Rajab MS, Rugutt JK, Fronczek FR, Fischer NH. 1997. Structural revision of harrisonin and 12-$\beta$-acetoxyharrisonin, two limonoids from Harrisonia abyssinica. J. Nat. Prod. 60: 822-825. https://doi.org/10.1021/np970201p
  15. Richardson MD. 2005. Changing patterns and trends in systemic fungal infections. J. Antimicrobial. Chemother. 56: i5-i11. https://doi.org/10.1093/jac/dki218
  16. Rugutt J, Rugutt KJ, Berner DK. 2001. Limonoids from Nigerian Harrisonia abyssinica and their stimulatory activity against Striga hermonthica seeds. J. Nat. Prod. 64: 1434-1438. https://doi.org/10.1021/np0100183
  17. Stephen C, Lester S, Black W, Fyfe M, Raverty S. 2002. Multispecies outbreak of cryptococcosis on southern Vancouver island, British Columbia. Can. Vet. J. 43: 792-794.
  18. Silveira FP, Husain S. 2007. Fungal infections in solid organ transplantation. Med. Mycol. 45: 305-320. https://doi.org/10.1080/13693780701200372

Cited by

  1. A Phenylpropanoid Glycoside as a Calcineurin Inhibitor Isolated from Magnolia obovata Thunb. vol.25, pp.9, 2014, https://doi.org/10.4014/jmb.1506.06031
  2. Anti-Arthritic Effect of Chebulanin on Collagen-Induced Arthritis in Mice vol.10, pp.9, 2014, https://doi.org/10.1371/journal.pone.0139052
  3. Inhibition of the Calcineurin Pathway by Two Flavonoids Isolated from Miliusa sinensis Finet & Gagnep. vol.26, pp.10, 2014, https://doi.org/10.4014/jmb.1605.05063
  4. A Leaf Extract of Harrisonia abyssinica Ameliorates Neurobehavioral, Histological and Biochemical Changes in the Hippocampus of Rats with Aluminum Chloride-Induced Alzheimer’s Disease vol.10, pp.6, 2014, https://doi.org/10.3390/antiox10060947