Alleviation of Podophyllotoxin Toxicity Using Coexisting Flavonoids from Dysosma versipellis

doi:10.1371/journal.pone.0072099

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药物发现与设计中心

	Alleviation of Podophyllotoxin Toxicity Using Coexisting Flavonoids from Dysosma versipellis
	Li, Juan 2,3; Sun, Hua 2; Jin, Lu 2,4; Cao, Wei 2; Zhang, Jin 1; Guo, Chong-Yi 2; Ding, Ke 1; Luo, Cheng4 ; Ye, Wen-Cai 2; Jiang, Ren-Wang 2
刊名	PLOS ONE
	2013-08-21
卷号	8 期号:8
ISSN号	1932-6203
DOI	10.1371/journal.pone.0072099
文献子类	Article
英文摘要	Podophyllotoxin (POD) is a lignan-type toxin existing in many herbs used in folk medicine. Until now, no effective strategy is available for the management of POD intoxication. This study aims to determine the protective effects of avonoids (quercetin and kaempferol) on POD-induced toxicity. In Vero cells, both avonoids protected POD-induced cytotoxicity by recovering alleviating G2/M arrest, decreasing ROS generation and changes of membrane potential, and recovering microtubule structure. In Swiss mice, the group given both POD and avonoids group had significantly lower mortality rate and showed less damages in the liver and kidney than the group given POD alone. As compared to the POD group, the POD plus avonoids group exhibited decreases in plasma transaminases, alkaline phosphatase, lactate dehydrogenase, plasma urea, creatinine and malondialdehyde levels, and increases in superoxide dismutase and glutathione levels. Histological examination of the liver and kidney showed less pathological changes in the treatment of POD plus avonoids group. The protective mechanisms were due to the antioxidant activity of avonoids against the oxidative stress induced by POD and the competitive binding of avonoids against POD for the same colchicines-binding sites. The latter binding was confirmed by the tubulin assembly assay in combination with molecular docking analyses. In conclusion, this study for the first time demonstrated that the coexisting flavonoids have great protective effects against the POD toxicity, and results of this study highlighted the great potential of searching for effective antidotes against toxins based on the pharmacological clues.
资助项目	National Natural Science Foundation of China[21072078] ; Doctoral Fund of Ministry of Education of China[20114401110005] ; Guangdong High Level Talent Scheme[00000000] ; Fundamental Research Funds for the Central Universities[21612603] ; Fundamental Research Funds for the Central Universities[21611398]
WOS关键词	NATURAL-PRODUCTS ; MICROTUBULE POLYMERIZATION ; CARDIOVASCULAR-DISEASE ; ARYLTETRALIN LIGNANS ; OXIDATIVE STRESS ; PROSTATE-CANCER ; GENE-EXPRESSION ; PC12 CELLS ; IN-VITRO ; QUERCETIN
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	PUBLIC LIBRARY SCIENCE
WOS记录号	WOS:000324470100079
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277499]
专题	药物发现与设计中心
通讯作者	Jiang, Ren-Wang
作者单位	1.Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Guangzhou 510530, Guangdong, Peoples R China 2.Jinan Univ, Inst Tradit Chinese Med & Nat Prod, Guangzhou, Guangdong, Peoples R China; 3.Hubei Univ Tradit Chinese Med, Key Lab Tradit Chinese Med Resource & Compound Pr, Wuhan, Peoples R China; 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab New Drug Res, Shanghai 200031, Peoples R China;
推荐引用方式 GB/T 7714	Li, Juan,Sun, Hua,Jin, Lu,et al. Alleviation of Podophyllotoxin Toxicity Using Coexisting Flavonoids from Dysosma versipellis[J]. PLOS ONE,2013,8(8).
APA	Li, Juan.,Sun, Hua.,Jin, Lu.,Cao, Wei.,Zhang, Jin.,...&Jiang, Ren-Wang.(2013).Alleviation of Podophyllotoxin Toxicity Using Coexisting Flavonoids from Dysosma versipellis.PLOS ONE,8(8).
MLA	Li, Juan,et al."Alleviation of Podophyllotoxin Toxicity Using Coexisting Flavonoids from Dysosma versipellis".PLOS ONE 8.8(2013).