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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

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

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