The antifungal activity and mechanisms of action of quantified extracts from berries, leaves and roots of Phytolacca tetramera

doi:10.1016/j.phymed.2019.152884

	The antifungal activity and mechanisms of action of quantified extracts from berries, leaves and roots of Phytolacca tetramera
	Butassi, Estefania 2; Svetaz, Laura A.2; Zhou, Shuaizhen 3,4,5; Wolfender, Jean-Luc 5; Cortes, Juan C. G.1,6; Ribas, Juan C.1,6; Diaz, Caridad 7; Perez-del Palacio, Jose 7; Vicente, Francisca 7; Zacchino, Susana A.2
刊名	PHYTOMEDICINE
	2019-07-01
卷号	60 页码:9
关键词	Phytolacca tetramera Quantified extracts Candida albicans Candida glabrata Phytolaccagenin Phytolaccoside B
ISSN号	0944-7113
DOI	10.1016/j.phymed.2019.152884
通讯作者	Zacchino, Susana A.(szaabgil@citynet.net.ar)
英文摘要	Background: Phytolacca tetramera is an endemic plant from Argentina that is currently at serious risk because its environment is subjected to a high anthropic impact. A previous study has shown that berry extracts obtained from this plant display antifungal activity against multiple human-pathogenic fungi when tested with a non-standardized method. Further evidences of the antifungal properties of other parts of the plant and studies of mechanism of antifungal action of the antifungal chemically characterized extracts are required. Purpose: This study aimed to gain further evidence of the antifungal activity of P. tetramera berry, leaf and root extracts in order to find the most active extract to be developed as an Herbal Medicinal Antifungal Product. The medicinal usefulness of P. tetramera extracts as antifungal agents will serve as an important support to create concience and carry out actions tending to the preservation of this threatened species and its environment. Materials and methods: Chemical analysis of all P. tetramera extracts, including quantitation of selected markers, was performed through UHPLC-ESI-MS/MS and UPLC-ESI-MS techniques according to the European Medicines Agency (EMA). The antifungal activity of the quantified extracts was tested with the standardized CLSI microbroth dilution method against Candida spp. Antifungal mechanisms of the most active extract were studied by examination of morphological changes by phase-contrast and fluorescence microscopies and both, cellular and enzymatic assays targeting either the fungal membrane or the cell wall. Results: The antifungal activity of twelve P. tetramera extracts was tested against Candida albicans and Candida glabrata. The dichloromethane extract from berries (PtDEb) showed the best activity. Phytolaccagenin (PhytG) and phytolaccoside B (PhytB) were selected as the main active markers for the antifungal P. tetramera extracts. The quantitation of these active markers in all extracts showed that PtDEb possessed the highest amount of PhytG and PhytB. Finally, studies on the mechanism of antifungal action showed that the most active PtDEb extract produces morphological changes compatible with a damage of the cell wall and/or the plasma membrane. Cellular and enzymatic assays showed that PtDEb would not damage the fungal cell wall by itself, but would alter the plasma membrane. In agreement, PtDEb was found to bind to ergosterol, the main sterol of the fungal plasma membrane. Conclusion: Studies of the anti-Candida activity of P. tetramera extracts led to the selection of PtDEb as the most suitable extract, confirming the antifungal properties of the threatened species P. tetramera. The new data give a valuable reason for the definitive protection of this sp. and its natural environment thus allowing further studies for the future development of an Herbal Medicinal Antifungal Product.
资助项目	Agencia Nacional de Promocion Cientifica y Tecnologica (ANPCyT)[PICT20141170] ; Agencia Nacional de Promocion Cientifica y Tecnologica (ANPCyT)[PICT2016-1833] ; National University of Rosario, Argentina (UNR) ; MINECO[BIO201569958-P] ; Junta de Castilla y Leon/FEDER, Spain[CSI068P17] ; Junta de Castilla y Leon/FEDER (Escalera de Excelencia), Spain[CLU-2017-03] ; Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET) ; Sino Swiss Science and Technology Cooperation Program (SSSTC)[IP18-092011] ; Fundacion MEDINA, a public-private partnership of Merck Sharp & Dohme de Espana S. A./Universidad de Granada/Junta de Andalucia, Spain
WOS关键词	ANTIBIOTICS ; INHIBITORS ; GLUCAN
WOS研究方向	Plant Sciences ; Pharmacology & Pharmacy ; Integrative & Complementary Medicine
语种	英语
出版者	ELSEVIER GMBH
WOS记录号	WOS:000485781500004
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/288660]
专题	中国科学院上海药物研究所
通讯作者	Zacchino, Susana A.
作者单位	1.Univ Salamanca, CSIC, Dept Microbiol & Genet, Salamanca 37007, Spain 2.Univ Nacl Rosario, Fac Ciencias Bioquim & Farmaceut, Area Farmacognosia, Suipacha 531, RA-2000 Rosario, Santa Fe, Argentina 3.Chinese Acad Sci, Shanghai Inst Mat Med, Nat Prod Chem Dept, Beijing, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Beijing, Peoples R China 5.Univ Lausanne, Univ Geneva, EPGL, Sch Pharmaceut Sci, CMU Rue Michel Servet 1, CH-1206 Geneva 4, Switzerland 6.Univ Salamanca, CSIC, Inst Biol Func & Genom, Salamanca 37007, Spain 7.Ctr Excelencia Invest Medicamentos Innovadores An, Fdn MEDINA, Parque Tecnol Ciencias Salud,Avda Conocimiento 34, E-18016 Granada, Spain
推荐引用方式 GB/T 7714	Butassi, Estefania,Svetaz, Laura A.,Zhou, Shuaizhen,et al. The antifungal activity and mechanisms of action of quantified extracts from berries, leaves and roots of Phytolacca tetramera[J]. PHYTOMEDICINE,2019,60:9.
APA	Butassi, Estefania.,Svetaz, Laura A..,Zhou, Shuaizhen.,Wolfender, Jean-Luc.,Cortes, Juan C. G..,...&Zacchino, Susana A..(2019).The antifungal activity and mechanisms of action of quantified extracts from berries, leaves and roots of Phytolacca tetramera.PHYTOMEDICINE,60,9.
MLA	Butassi, Estefania,et al."The antifungal activity and mechanisms of action of quantified extracts from berries, leaves and roots of Phytolacca tetramera".PHYTOMEDICINE 60(2019):9.