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KMID : 0545120140240101377
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Journal of Microbiology and Biotechnology
2014 Volume.24 No. 10 p.1377 ~ p.1381
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Inhibition of the Calcineurin Pathway by Two Tannins, Chebulagic Acid and Chebulanin, Isolated from Harrisonia abyssinica Oliv.
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Lee Won-Jeong
Moon Jae-Sun
Kim Sung-In
Kim Young-Tae
Oyekanmi Nash
Bahn Yong-Sun
Kim Sung-Uk
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Abstract
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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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KEYWORD
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Signaling pathway, Cryptococcus neoformans, Two-component system, Calcineurin inhibitor, Antifungal activity
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