基于粗糙集理论构建“谱毒”关系研究何首乌特异质肝毒性物质基础
|
摘要
何首乌特异质肝毒性是行业关注的热点问题之一。该研究采用MTT法和流式细胞术筛选出何首乌特异质肝毒性最强的毒性部位为其醇提液大孔吸附树脂50%乙醇洗脱部位(简称何首乌50%乙醇部位);采用HPLC建立不同产地生/制何首乌50%乙醇部位指纹图谱,有14个共有峰;采用MTT法检测上述样品对人正常肝脏LO2细胞的生长抑制率;通过粗糙集理论进行二者的"谱毒"相关性分析,预测出对特异质肝毒性有贡献的2个主要峰,其中贡献最大的为二苯乙烯苷;体外特异质肝毒性验证实验结果表明二苯乙烯苷是何首乌特异质肝毒性的主要物质基础。以上研究结果对揭示何首乌特异质肝毒性物质基础具有现实意义,同时也表明粗糙集理论可以较好地应用至何首乌"谱毒"研究,为开展中药药效/毒性物质基础提供一种新的方法。
Idiosyncratic hepatotoxicity of Polygonum multiflorum has attracted a great attention in the world. The most toxic part of idiosyncratic hepatotoxicity was screened by MTT assay and flow cytometry, which was the 50% ethanol elute by macroporous adsorptive resins from alcohol-extraction of P. multiflorum. The fingerprints were collected by HPLC from 50% ethanol elute of crude and processed P. multiflorum from different habitats, then 14 common peaks were determined. Spectrum-toxicity relationship was analyzed by rough set theory(RST). Two main chemical components were predicted for idiosyncratic hepatotoxicity, in which TSG was the greater contributor. Idiosyncratic hepatotoxicity of TSG was tested in vitro, and the results indicated that TSG was the most important constituent contributed to idiosyncratic hepatotoxicity of P. multiflorum. The study showed the discovery of the main chemical components for idiosyncratic hepatotoxicity, and RST was effective for analyzing the spectrum-toxicity relationship, which could be a new method used in the effective/toxic constituents field of traditional Chinese medicine.
Idiosyncratic hepatotoxicity of Polygonum multiflorum has attracted a great attention in the world. The most toxic part of idiosyncratic hepatotoxicity was screened by MTT assay and flow cytometry, which was the 50% ethanol elute by macroporous adsorptive resins from alcohol-extraction of P. multiflorum. The fingerprints were collected by HPLC from 50% ethanol elute of crude and processed P. multiflorum from different habitats, then 14 common peaks were determined. Spectrum-toxicity relationship was analyzed by rough set theory(RST). Two main chemical components were predicted for idiosyncratic hepatotoxicity, in which TSG was the greater contributor. Idiosyncratic hepatotoxicity of TSG was tested in vitro, and the results indicated that TSG was the most important constituent contributed to idiosyncratic hepatotoxicity of P. multiflorum. The study showed the discovery of the main chemical components for idiosyncratic hepatotoxicity, and RST was effective for analyzing the spectrum-toxicity relationship, which could be a new method used in the effective/toxic constituents field of traditional Chinese medicine.
引文
[1] 中国药典.一部[S]. 2015:175.
[2] Lin L F, Ni B R, Lin H M, et al. Traditional usages, botany, phytochemistry, pharmacology and toxicology of Polygonum multiflorum Thunb.: a review[J]. J Ethnopharmacol, 2015, 159:158.
[3] 李晓菲, 李娜, 涂灿, 等. 基于内毒素特异质模型的生首乌与制首乌肝毒性比较研究[J]. 中草药, 2015, 46(10):1481.
[4] Wu X, Chen X, Huang Q, et al.Toxicity of raw and processed roots of Polygonum multiflorum[J]. Fitoterapia, 2012, 83(3):469.
[5] 袁炜,高增平,杨建波,等.何首乌化学成分的研究[J].中草药,2017,48(4):631.
[6] 高淑红, 苏珍枝, 肖学凤. 制首乌化学成分及药理作用研究进展[J]. 山西中医学院学报, 2012,23(2):6.
[7] Yin L Z, Gui W H, Yang C H, et al. Core set analysis in inconsistent desicion tables, information sciences [J]. In Sci, 2013, 241(12): 138.
[8] 聂磊, 仲红波, 向兰, 等.粗糙集方法选取相关特征峰用于黄芪药材的产地鉴别 [J].中药材, 2006, 29(10): 1020.
[9] 尹林子, 阳春华, 王晓丽, 等. 基于标记可辨识矩阵的增量式属性约简算法 [J]. 自动化学报, 2014, 40(3): 397.
[10] 张立军, 李芸, 戴海蓉, 等. 高乌头不同溶剂萃取部分急性毒性的谱-毒关系研究[J].中国临床药理学杂志,2018,34(4):470.
[11] 李婷婷, 李瑞红, 刘振兴, 等. 基于类器官3D培养的何首乌易感物质肝毒性评价[J]. 药学学报, 2017,52(7):1048.
[12] Tamura M, Koshibe Y, Kaji K, et al. Attempt to synthesize 2,3,5,4′-tetrahydroxystilbene derived from 2,3,5,4′-tetrahydroxystilbene-2-O-β-glucoside (THSG)[J]. Chem Pharm Bull, 2015, 63(2):122.
[13] 李丹丹. 3D肝毒性评价模型的建立及何首乌肝毒性机制的初步探索[D]. 南宁:广西医科大学, 2016.
[14] 林龙飞. 何首乌致肝损伤成分及作用机制研究[D]. 北京:北京中医药大学, 2016.
[15] Kim H K, Choi Y H, Choi J S, et al. A new stilbene glucoside gallate from the rots of Polygonum multiflorum[J]. Arch Pharm Res, 2008, 31(10):1225.
[16] 李娜, 宋捷, 李晓, 等. 药物代谢酶抑制剂对反式二苯乙烯苷所致肝损伤易感性的影响[J].药学学报, 2017, 52 (7): 1063.
[17] 孙晋芩, 黄晓兰, 吴惠勤, 等.何首乌中顺式和反式-二苯乙烯苷的HPLC/DAD/MS测定及其光稳定性考察[J].中国药学杂志, 2009, 44(7): 541.
[18] 张乐, 柏兆方, 李春雨, 等. 制首乌中顺式二苯乙烯苷转化量与特异质肝损伤的相关性研究[J]. 药学学报, 2017, 52 (7): 1041.
[19] 徐男,时海燕,李晓宇,等.何首乌制剂不良反应研究进展与成因分析[J].中国实验方剂学杂志,2017,23(4):208.
[2] Lin L F, Ni B R, Lin H M, et al. Traditional usages, botany, phytochemistry, pharmacology and toxicology of Polygonum multiflorum Thunb.: a review[J]. J Ethnopharmacol, 2015, 159:158.
[3] 李晓菲, 李娜, 涂灿, 等. 基于内毒素特异质模型的生首乌与制首乌肝毒性比较研究[J]. 中草药, 2015, 46(10):1481.
[4] Wu X, Chen X, Huang Q, et al.Toxicity of raw and processed roots of Polygonum multiflorum[J]. Fitoterapia, 2012, 83(3):469.
[5] 袁炜,高增平,杨建波,等.何首乌化学成分的研究[J].中草药,2017,48(4):631.
[6] 高淑红, 苏珍枝, 肖学凤. 制首乌化学成分及药理作用研究进展[J]. 山西中医学院学报, 2012,23(2):6.
[7] Yin L Z, Gui W H, Yang C H, et al. Core set analysis in inconsistent desicion tables, information sciences [J]. In Sci, 2013, 241(12): 138.
[8] 聂磊, 仲红波, 向兰, 等.粗糙集方法选取相关特征峰用于黄芪药材的产地鉴别 [J].中药材, 2006, 29(10): 1020.
[9] 尹林子, 阳春华, 王晓丽, 等. 基于标记可辨识矩阵的增量式属性约简算法 [J]. 自动化学报, 2014, 40(3): 397.
[10] 张立军, 李芸, 戴海蓉, 等. 高乌头不同溶剂萃取部分急性毒性的谱-毒关系研究[J].中国临床药理学杂志,2018,34(4):470.
[11] 李婷婷, 李瑞红, 刘振兴, 等. 基于类器官3D培养的何首乌易感物质肝毒性评价[J]. 药学学报, 2017,52(7):1048.
[12] Tamura M, Koshibe Y, Kaji K, et al. Attempt to synthesize 2,3,5,4′-tetrahydroxystilbene derived from 2,3,5,4′-tetrahydroxystilbene-2-O-β-glucoside (THSG)[J]. Chem Pharm Bull, 2015, 63(2):122.
[13] 李丹丹. 3D肝毒性评价模型的建立及何首乌肝毒性机制的初步探索[D]. 南宁:广西医科大学, 2016.
[14] 林龙飞. 何首乌致肝损伤成分及作用机制研究[D]. 北京:北京中医药大学, 2016.
[15] Kim H K, Choi Y H, Choi J S, et al. A new stilbene glucoside gallate from the rots of Polygonum multiflorum[J]. Arch Pharm Res, 2008, 31(10):1225.
[16] 李娜, 宋捷, 李晓, 等. 药物代谢酶抑制剂对反式二苯乙烯苷所致肝损伤易感性的影响[J].药学学报, 2017, 52 (7): 1063.
[17] 孙晋芩, 黄晓兰, 吴惠勤, 等.何首乌中顺式和反式-二苯乙烯苷的HPLC/DAD/MS测定及其光稳定性考察[J].中国药学杂志, 2009, 44(7): 541.
[18] 张乐, 柏兆方, 李春雨, 等. 制首乌中顺式二苯乙烯苷转化量与特异质肝损伤的相关性研究[J]. 药学学报, 2017, 52 (7): 1041.
[19] 徐男,时海燕,李晓宇,等.何首乌制剂不良反应研究进展与成因分析[J].中国实验方剂学杂志,2017,23(4):208.