Advanced
A Phenylpropanoid Glycoside as a Calcineurin Inhibitor Isolated from Magnolia obovata Thunb.
A Phenylpropanoid Glycoside as a Calcineurin Inhibitor Isolated from Magnolia obovata Thunb.
Journal of Microbiology and Biotechnology. 2015. Sep, 25(9): 1429-1432
Copyright © 2015, The Korean Society For Microbiology And Biotechnology
  • Received : June 12, 2015
  • Accepted : June 24, 2015
  • Published : September 28, 2015
Download
PDF
e-PUB
PubReader
PPT
Export by style
Article
Author
Metrics
Cited by
TagCloud
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
Yong-Sun Bahn
Department of Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea
Hanna Lee
Korea Promotion Institute for Traditional Medicine Industry, Gyeongsan 712-260, Republic of Korea
Tae Hoon Kang
Korea Promotion Institute for Traditional Medicine Industry, Gyeongsan 712-260, Republic of Korea
Heung Mook Shin
Korea Promotion Institute for Traditional Medicine Industry, Gyeongsan 712-260, 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
To identify plant-derived cell signaling inhibitors with antifungal properties, a twocomponent screening system using both wild-type Cryptococcus neoformans and a calcineurin mutant was employed owing to their counter-regulatory actions on the Hog1 mitogenactivated protein kinase and calcineurin pathways. Of the 2,000 plant extracts evaluated, a single bioactive compound from M. obovata Thunb. was found to act specifically on the calcineurin pathway of C. neoformans . This compound was identified as magnoloside A, and had potent antifungal activities against various Cryptococcus strains with minimum inhibitory concentration values ranging from 1.0 to 4.0 μg/ml.
Keywords
PPT Slide
Lager Image
PPT Slide
Lager Image
PPT Slide
Lager Image
Acknowledgements
We thank the International Biological Material Research Center (IMBRC), Korea Research Institute of Bioscience and Biotechnology and Korea Promotion Institute for Traditional Medicine Industry (KOTMIN) for providing various plant extracts.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).
References
Breuder T , Hemenway CS , Movva NR , Cardenas ME , Heitman J 1994 Calcineurin is essential in cyclosporine Aand FK506-sensitive yeast strains. Proc. Natl. Acad. Sci. USA 91 5372 - 5376    DOI : 10.1073/pnas.91.12.5372
Chang BS , Lee YM , Ku Y , Bae KH , Chung CP 1998 Antimicrobial activity of magnolol and honokiol against periodontopathic microorganisms. Planta Med. 64 367 - 369    DOI : 10.1055/s-2006-957453
Clinical and Laboratory Standards Institute. 2008 Reference methods for broth dilution antifungal susceptibility testing of yeasts 3rd Ed. Clinical and Laboratory Standards Institute Pennsylvania CLSI document M27-A3 1 - 20
Fong WF , Tse AKW , Poon KH , Wang C 2005 Magnolol and honokiol enhance HL-60 human leukemia cell differentiation induced by 1,25-dihydroxyvitamin D3 and retinoic acid. Int. J. Biochem. Cell Biol. 37 427 - 441    DOI : 10.1016/j.biocel.2004.05.021
Hasegawa T , Fukuyama Y , Yamada T , Nakagawa K 1988 Isolation and structure of magnoloside A, a new phenylpropanoid glycoside fromMagnolia obovataThunb. Chem. Lett. 17 163 - 166    DOI : 10.1246/cl.1988.163
Hull CM , Heitman J 2002 Genetics ofCryptococcus neoformans. Annu. Rev. Genet. 36 557 - 615    DOI : 10.1146/annurev.genet.36.052402.152652
Hwang EI , Kwon BM , Lee SH , Kim NR , Kang TH , Kim YT 2002 Obovatols, new chitin synthase 2 inhibitors ofSaccharomyces cerevisiaefromMagnolia obovata. J. Antimicrob. Chemother. 49 95 - 101    DOI : 10.1093/jac/49.1.95
Idnurm A , Bahn YS , Nielsen K , Lin X , Fraser JA , Heitman J 2005 Deciphering the model pathogenic fungusCryptococcus neoformans. Nat. Rev. Microbiol. 3 753 - 764    DOI : 10.1038/nrmicro1245
Kojima K , Bahn YS , Heitman J 2006 Calcineurin, Mpk1 and Hog1 MAPK pathways independently control fludioxonil antifungal sensitivity inCryptococcus neoformans. Microbiology 152 591 - 604    DOI : 10.1099/mic.0.28571-0
Klee CB , Crouch TH , Krinks MH 1979 Calcineurin: a calcium- and calmodulin-binding protein of the nervous system. Proc. Natl. Acad. Sci. USA 76 6270 - 6273    DOI : 10.1073/pnas.76.12.6270
Lee SY , Co JS , Yuk DY , Moon DC , Jung JK , Yoo HS 2009 Obovatol enhances docetaxel-induced prostate and colon cancer cell death through inactivation of nuclear transcription factor-κB. J. Pharmacol. Sci. 111 124 - 136    DOI : 10.1254/jphs.09048FP
Lee WJ , Moon JS , Kim SI , Kim YT , Nash O , Bahn YS , Kim SU 2014 Inhibition of the calcineurin pathway by two tannins, chebulagic acid and chebulanin, isolated fromHarrisonia abyssinicaOliv. J. Microbiol. Biotechnol. 24 1377 - 1381    DOI : 10.4014/jmb.1405.05030
Lee YJ , Lee YM , Lee CK , Jung JK , Han SB , Hong JT 2011 Therapeutic applications of compounds in theMagnoliafamily. Pharmacol. Ther. 130 157 - 176    DOI : 10.1016/j.pharmthera.2011.01.010
Liu J , Farmer JD , Lane WS , Friedman J , Weissman I , Schreiber SL 1991 Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes. Cell 66 807 - 815    DOI : 10.1016/0092-8674(91)90124-H
Mitchell TG , Perfect JR 1995 Cryptococcosis in the era of AIDS - 100 years after the discovery ofCryptococcus neoformans. Clin. Microbiol. Rev. 8 515 - 548
Park BJ , Wannemuehler KA , Marston BJ , Govender N , Pappas PG , Chiller TM 2009 Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS. AIDS 23 525 - 530    DOI : 10.1097/QAD.0b013e328322ffac
Park ES , Lim Y , Lee SH , Kwon BM , Yoo HS , Hong JT , Yun YP 2011 Antiplatelet activity of obovatol, a biphenolic component ofMagnolia obovata, in rat arterial thrombosis and rabbit platelet aggregation. J. Atheroscler. Thromb. 18 659 - 669    DOI : 10.5551/jat.7427
Perfect JR , Dismukes WE , Dromer F , Goldman DL , Graybill JR , Hamill RJ 2010 Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious disease society of America. Clin. Infect. Dis. 50 291 - 322    DOI : 10.1086/649858
Poor F , Parent SA , Morin N , Dahl AM , Ramadan N , Chrebet G 1992 Calcineurin mediates inhibition by FK506 and cyclosporine of recovery from α-factor arrest in yeast. Nature 360 682 - 684    DOI : 10.1038/360682a0
Prokisch H , Yarden O , Dieminger M , Troschug M , Barthelmess IB 1997 Impairment of calcineurin function inNeurospora crassareveals its essential role in hyphal growth, morphology and maintenance of the apical Ca2+gradient. Mol. Gen. Genet. 256 104 - 114    DOI : 10.1007/s004380050551
Rasmussen C , Garen C , Brining S , Kincaid RL , Means RL , Means AR 1994 The calmodulin-dependent protein phosphatase catalytic subunit (calcineurin A) is an essential gene inApergillus nidulans. EMBO J. 13 2545 - 2552
Singh N , Husain S 2000 Infections of the central nervous system in transplant recipients. Transpl. Infect. Dis. 2 101 - 111    DOI : 10.1034/j.1399-3062.2000.020302.x
Speed B , Dunt D 1995 Clinical and host differences between infections with the two varieties ofCryptococcus neoformans. Clin. Infect. Dis. 21 28 - 36    DOI : 10.1093/clinids/21.1.28
Steinbach WJ , Reedy JL , Cramer Jr RA , Perfect JR , Heitman J 2007 Harnessing calcineurin as a novel anti-infective agent against invasive fungal infections. Nat. Rev. Microbiol. 5 418 - 430    DOI : 10.1038/nrmicro1680
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
Tachikawa E , Takahashi M , Kashimoto T 2000 Effects of extract and ingredients isolated fromMagnolia obovataThunberg on catecholamine secretion from bovine adrenal chromaffin cells. Biochem. Pharmacol. 60 433 - 440    DOI : 10.1016/S0006-2952(00)00343-9