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Inhibition of the Calcineurin Pathway by Two Tannins, Chebulagic Acid and Chebulanin, Isolated from Harrisonia abyssinica Oliv.
Inhibition of the Calcineurin Pathway by Two Tannins, Chebulagic Acid and Chebulanin, Isolated from Harrisonia abyssinica Oliv.
Journal of Microbiology and Biotechnology. 2014. Oct, 24(10): 1377-1381
Copyright © 2014, The Korean Society For Microbiology And Biotechnology
  • Received : May 14, 2014
  • Accepted : July 07, 2014
  • Published : October 28, 2014
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About the Authors
Won Jeong Lee
Division of Biosystems Research, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea
Jae Sun Moon
Division of Biosystems Research, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea
Sung In Kim
Division of Biosystems Research, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea
Young Tae Kim
Division of Biosystems Research, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea
Oyekanmi Nash
Southwest Biotechnology Center of Excellence, Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Nigeria
Yong-Sun Bahn
Department of Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea
Sung Uk Kim
Division of Biosystems Research, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea
kimsu@kribb.re.kr

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 μg/ml.
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Acknowledgements
This work was supported by a grant from Procurement and Development of Foreign Biological Resources funded by the Ministry of Science, ICT and Future Planning of the Korean government (NRF-2011-00495).
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