Full Text:   <2619>

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CLC number: R285.5

On-line Access: 2017-09-05

Received: 2016-04-28

Revision Accepted: 2016-09-17

Crosschecked: 2017-08-17

Cited: 0

Clicked: 4801

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Zhong-ping Deng

http://orcid.org/0000-0002-5608-8641

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Journal of Zhejiang University SCIENCE B 2017 Vol.18 No.9 P.757-769

http://doi.org/10.1631/jzus.B1600158


Toxicity comparison of different active fractions extracted from radix Sophorae tonkinensis in zebrafish


Author(s):  Hong-cui Liu, Xiao-yu Zhu, Jiang-hua Chen, Sheng-ya Guo, Chun-qi Li, Zhong-ping Deng

Affiliation(s):  Center for Drug Safety Evaluation and Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; more

Corresponding email(s):   jackli@zhunter.com, dzp@shutcm.edu.cn

Key Words:  Sophorae tonkinensis Gagnep, Active fraction, Hepatotoxicity, Cardiovascular toxicity, Zebrafish


Hong-cui Liu, Xiao-yu Zhu, Jiang-hua Chen, Sheng-ya Guo, Chun-qi Li, Zhong-ping Deng. Toxicity comparison of different active fractions extracted from radix Sophorae tonkinensis in zebrafish[J]. Journal of Zhejiang University Science B, 2017, 18(9): 757-769.

@article{title="Toxicity comparison of different active fractions extracted from radix Sophorae tonkinensis in zebrafish",
author="Hong-cui Liu, Xiao-yu Zhu, Jiang-hua Chen, Sheng-ya Guo, Chun-qi Li, Zhong-ping Deng",
journal="Journal of Zhejiang University Science B",
volume="18",
number="9",
pages="757-769",
year="2017",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1600158"
}

%0 Journal Article
%T Toxicity comparison of different active fractions extracted from radix Sophorae tonkinensis in zebrafish
%A Hong-cui Liu
%A Xiao-yu Zhu
%A Jiang-hua Chen
%A Sheng-ya Guo
%A Chun-qi Li
%A Zhong-ping Deng
%J Journal of Zhejiang University SCIENCE B
%V 18
%N 9
%P 757-769
%@ 1673-1581
%D 2017
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1600158

TY - JOUR
T1 - Toxicity comparison of different active fractions extracted from radix Sophorae tonkinensis in zebrafish
A1 - Hong-cui Liu
A1 - Xiao-yu Zhu
A1 - Jiang-hua Chen
A1 - Sheng-ya Guo
A1 - Chun-qi Li
A1 - Zhong-ping Deng
J0 - Journal of Zhejiang University Science B
VL - 18
IS - 9
SP - 757
EP - 769
%@ 1673-1581
Y1 - 2017
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1600158


Abstract: 
Radix Sophorae tonkinensis (RST) is a widely used herb in Traditional Chinese Medicine (TCM) for treating infectious and inflammatory diseases. However, the toxicity data for RST are limited. The aim of this work is to assess and compare the toxicity of the whole RST extract and its five active fractions using the zebrafish model. Five active fractions of RST were prepared using five different types of solvents, which included dealkalized water, ethanol, n-butyl ethanol, dichloromethane, and diethyl ether. The chemical profiles of the active fractions were determined by high-performance liquid chromatography (HPLC), and the toxicity observed in the zebrafish model was confirmed using mouse models. In the zebrafish model, cardiovascular toxicity was observed for the fraction extracted using diethyl ether, and hepatotoxicity was observed for the whole RST extract and the fractions extracted using water and ethanol, whereas both cardiovascular and hepatic toxicities were observed for the fractions extracted using n-butyl ethanol and dichloromethane. The hepatotoxicity of the fractions extracted using n-butyl ethanol and dichloromethane was also observed in mice. Our findings provide the toxicity data for RST and its five active fractions through modeling in a zebrafish, and indicate that the different fractions may each have a different toxicity, which is helpful for the optimal use of RST in clinical practice.

使用斑马鱼模型比较山豆根不同有效部位的毒性

目的:利用斑马鱼模型评价和比较山豆根不同提取方法提取的有效部位的体内毒性。
创新点:首次在斑马鱼模型中证明山豆根提取方法不同,有效部位的毒性有明显差异。研究结果有助于指导山豆根的新药开发与临床应用。
方法:用五种不同的溶剂(去碱水、乙醇、正丁基乙醇、二氯甲烷和乙醚)提取山豆根,然后通过高效液相色谱法(HPLC)检测有效部位,将AB品系斑马鱼分为对照组(养鱼水处理)和实验组(山豆根提取物)。实验组根据采用的提取溶剂不同,分为以下六组:去碱水提取组、乙醇沉提取组、正丁基乙醇提取组、二氯甲烷提取组和乙醚提取组以及山豆根总组分组(对照),观察各种山豆根提取物对斑马鱼的急性毒性与毒性靶器官。
结论:山豆根乙醚提取组诱发斑马鱼心血管毒性(图1);山豆根去碱水提取组、乙醇沉提取组以及山豆根总组分组诱发斑马鱼肝脏毒性(图3和图4);而山豆根正丁基乙醇提取组和二氯甲烷提取组诱发斑马鱼心血管毒性(图1和图2)和肝脏毒性(图3和图4)。

关键词:山豆根;有效部位;肝脏毒性;心血管毒性;斑马鱼

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]Chai, N.L., Fu, Q., Shi, H., et al., 2012. Oxymatrine liposome attenuates hepatic fibrosis via targeting hepatic stellate cells. World J. Gastroenterol., 18(31):4199-4206.

[2]Cho, C.H., Chuang, C.Y., Chen, C.F., 1986. Study of the antipyretic activity of matrine. A lupin alkaloid isolated from Sophora subprostrata. Planta Med., 52(5):343-345.

[3]Chui, C.H., Lau, F.Y., Tang, J.C., et al., 2005. Activities of fresh juice of Scutellaria barbata and warmed water extract of Radix Sophorae Tonkinensis on anti-proliferation and apoptosis of human cancer cell lines. Int. J. Mol. Med., 16(2):337-341.

[4]CPC (Chinese Pharmacopoeia Commission), 2015. Pharmacopoeia of the People’s Republic of China (Part I). China Medical Science Press, Beijing, China, p.25-26 (in Chinese).

[5]Ding, P.L., Chen, D.F., 2006. Isoprenylated flavonoids from the roots and rhizomes of Sophora tonkinensis. Helv. Chim. Acta, 89(1):103-110.

[6]Ding, P.L., Huang, H., Zhou, P., et al., 2006. Quinolizidine alkaloids with anti-HBV activity from Sophora tonkinensis. Planta Med., 72(9):854-856.

[7]He, C.M., Cheng, Z.H., Chen, D.F., 2013. Qualitative and quantitative analysis of flavonoids in Sophora tonkinensis by LC/MS and HPLC. Chin. J. Nat. Med., 11(6):690-698.

[8]He, J.H., Guo, S.Y., Zhu, F., et al., 2013. A zebrafish phenotypic assay for assessing drug-induced hepatotoxicity. J. Pharmacol. Toxicol. Methods, 67(1):25-32.

[9]Hill, A., 2011. Hepatotoxicity testing in larval zebrafish. In: McGrath, P. (Ed.), Zebrafish: Methods for Assessing Drug Safety and Toxicity. John Wiley & Sons, Inc., Hoboken, NJ, USA, p.89-102.

[10]Hill, A.J., Teraoka, H., Heideman, W., et al., 2005. Zebrafish as a model vertebrate for investigating chemical toxicity. Toxicol. Sci., 86(1):6-19.

[11]Hill, A., Ball, J., Jones, M., et al., 2008. Implementation of zebrafish toxicity testing between in vitro and in vivo models to advance candidate selection. The 29th Annual Meeting of the American College of Toxicology, Tucson, AZ, USA, p.9-12.

[12]Hill, A., Mesens, N., Steemans, M., et al., 2012. Comparisons between in vitro whole cell imaging and in vivo zebrafish-based approaches for identifying potential human hepatotoxicants earlier in pharmaceutical development. Drug Metab. Rev., 44(1):127-140.

[13]Jones, K.S., Alimov, A.P., Rilo, H.L., et al., 2008. A high throughput live transparent animal bioassay to identify non-toxic small molecules or genes that regulate vertebrate fat metabolism for obesity drug development. Nutr. Metab. (Lond.), 5:23.

[14]Kimmel, C.B., Ballard, W.W., Kimmel, S.R., et al., 1995. Stages of embryonic development of the zebrafish. Dev. Dynam., 203(3):253-310.

[15]Lee, J.W., Lee, J.H., Lee, C., et al., 2015. Inhibitory constituents of Sophora tonkinensis on nitric oxide production in RAW 264.7 macrophages. Bioorg. Med. Chem. Lett., 25(4):960-962.

[16]Li, S.J., Yang, J., Qian, X.L., et al., 2011. Experimental study on chronic toxicity in rats caused by water extract components of radix et Rhizoma Sophorae tonkinensise. Chin. J. Pharmacovigil., 8(2):89-92 (in Chinese).

[17]Li, X.N., Sha, N., Yan, H.X., et al., 2008a. Isoprenylated flavonoids from the roots of Sophora tonkinensis. Phytochem. Lett., 1(3):163-167.

[18]Li, X.N., Lu, Z.Q., Chen, G.T., et al., 2008b. NMR spectral assignments of isoprenylated flavanones from Sophora tonkinensis. Magn. Reson. Chem., 46(9):898-902.

[19]Li, X., Luan, Y., Li, X., 2012. Study on anti-inflammatory efficacy accompanied by side effects of different components of Sophorae tonkinensis radix et Rhizoma. China J. Chin. Mater. Med., 37(15):2232-2237 (in Chinese).

[20]Liu, X.S., Jiang, J., Jiao, X.Y., et al., 2006. Matrine-induced apoptosis in leukemia U937 cells: involvement of caspases activation and MAPK-independent pathways. Planta Med., 72(6):501-506.

[21]Long, Y., Lin, X.T., Zeng, K.L., et al., 2004. Efficacy of intramuscular matrine in the treatment of chronic hepatitis B. Hepatobiliary Pancreat. Dis. Int., 3(1):69-72.

[22]McGrath, P., Li, C.Q., 2008. Zebrafish: a predictive model for assessing drug-induced toxicity. Drug Discov. Today, 13(9-10):394-401.

[23]Pan, Q.M., Li, Y.H., Hua, J., et al., 2015. Antiviral matrine-type alkaloids from the rhizomes of Sophora tonkinensis. J. Nat. Prod., 78(7):1683-1688.

[24]Qian, H., Zhao, B.T., Chan, B., et al., 2015. Relationship between the content of polysaccharides, flavonoids and polyphenols from the sporocarp of Phellinus linteus and the antioxidant activity. Sci. Technol. Food Ind., 36(12):104-108 (in Chinese).

[25]Rekha, R.D., Amali, A.A., Her, G.M., et al., 2008. Thioacetamide accelerates steatohepatitis, cirrhosis and HCC by expressing HCV core protein in transgenic zebrafish Danio rerio. Toxicology, 243(1-2):11-22.

[26]Selderslaghs, I.W.T., Blust, R., Witters, H.E., 2012. Feasibility study of the zebrafish assay as an alternative method to screen for developmental toxicity and embryotoxicity using a training set of 27 compounds. Reprod. Toxicol., 33(2):142-154.

[27]Shen, B., Liu, H.C., Ou, W.B., et al., 2015. Toxicity induced by Basic Violet 14, Direct Red 28 and Acid Red 26 in zebrafish larvae. J. Appl. Toxicol., 35(12):1473-1480.

[28]Sun, R., Yang, Q., Zhao, Y., 2010. Comparative study on acute toxicity of different components of radix et Rhizome Sophorae Tonkinensis in mice. Chin. J. Pharmacovigil., 7(5):257-262 (in Chinese).

[29]Tang, L., Dong, L.N., Peng, X.J., et al., 2013. Pharmacokinetic characterization of oxymatrine and matrine in rats after oral administration of radix Sophorae tonkinensis extract and oxymatrine by sensitive and robust UPLC-MS/MS method. J. Pharm. Biomed. Anal., 83:179-185.

[30]Wang, S.H., Li, T.F., Ran, B.D., et al., 2004. Analysis on contents of organic acids and volatile components in tabacco leaves of Yunnan Province. Chin. Tob. Sci., (2):35-37 (in Chinese).

[31]Westerfield, M., 1995. The Zebrafish Book: A Guide for the Laboratory Use of Zebrafish (Danio rerio). University of Oregon Press, Eugene, OR, USA.

[32]Xiao, P., Kubo, H., Komiya, H., et al., 1999. (−)-14β-Acetoxymatrine and (+)-14α-acetoxymatrine, two new matrine-type lupin alkaloids from the leaves of Sophora tonkinensis. Chem. Pharm. Bull. (Tokyo), 47(3):448-450.

[33]Yang, Q., Zheng, L.N., Xie, Y.Z., et al., 2010. Study on the “dosage-time-toxicity” relationship of hepatotoxicity induced by different components of radix et Rhizoma Sophorae Tonkinensis in mice. Chin. J. Pharmacovigil., 7(7):385-389 (in Chinese).

[34]Yoo, H., Chae, H.S., Kim, Y.M., et al., 2014. Flavonoids and arylbenzofurans from the rhizomes and roots of Sophora tonkinensis with IL-6 production inhibitory activity. Bioorg. Med. Chem. Lett., 24(24):5644-5647.

[35]Zhang, C., Willett, C., Fremgen, T., 2003. Zebrafish: an animal model for toxicological studies. Curr. Protoc. Toxicol., 17: 1.7.1-1.7.18.

[36]Zhang, H.Y., Ding, T.H., 2013. Survey of clinical application and toxic reaction of shandougen. Western J. Tradit. Chin. Med., 26(3):121-124 (in Chinese).

[37]Zhou, H.J., Ma, H.L., Guo, D.Z., et al., 2015. Physicochemical properties and antioxidant activity of intracellular polysaccharides from Phellinus igniarius precipitated by different ethanol concentrations. Food Sci., 36(19):34-38 (in Chinese).

[38]Zhou, J., Guo, S.Y., Zhang, Y., et al., 2014. Human prokinetic drugs promote gastrointestinal motility in zebrafish. Neurogastroenterol. Motil., 26(4):589-595.

[39]Zhu, J.J., Xu, Y.Q., He, J.H., et al., 2014. Human cardiotoxic drugs delivered by soaking and microinjection induce cardiovascular toxicity in zebrafish. J. Appl. Toxicol., 34(2):139-148.

[40]Zhu, X.Y., Liu, H.C., Guo, S.Y., et al., 2016. A zebrafish thrombosis model for assessing antithrombotic drugs. Zebrafish, 13(4):335-344.

[41]Zon, L.I., Peterson, R.T., 2005. In vivo drug discovery in the zebrafish. Nat. Rev. Drug Discov., 4(1):35-44.

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