药学学报, 2019, 54(12): 2141-2148
引用本文:
谭鹏, 王伽伯, 张定堃, 周永峰, 牛明, 王梅, 赵军宁, 肖小河. 效应成分指数在中药大黄质量评价中的应用研究[J]. 药学学报, 2019, 54(12): 2141-2148.
TAN Peng, WANG Jia-bo, ZHANG Ding-kun, ZHOU Yong-feng, NIU Ming, WANG Mei, ZHAO Jun-ning, XIAO Xiao-he. Application of an effect-constituents index for the quality evaluation of the traditional Chinese medicine rhubarb[J]. Acta Pharmaceutica Sinica, 2019, 54(12): 2141-2148.

效应成分指数在中药大黄质量评价中的应用研究
谭鹏1,2, 王伽伯3, 张定堃2, 周永峰3, 牛明3, 王梅4, 赵军宁1, 肖小河3
1. 四川省中医药科学院国家中医药管理局中药质量生物评价重点研究室, 四川 成都 610041;
2. 成都中医药大学药学院, 四川 成都 611137;
3. 中国人民解放军总医院第五医学中心, 全军中医药研究所, 北京 100039;
4. 莱顿大学, LU-欧洲中医药与天然产物研究中心, 荷兰 莱顿 2333 BE
摘要:
探讨效应成分指数在大黄质量评价中的应用研究。采用超高效液相色谱法同时测定大黄中12个化学成分的含量,采用ICR小鼠便秘模型测定12个化学成分的致泻生物效价,以番泻苷A的致泻生物效价为基准,其余11个化学成分的泻下生物效价与之相比,得到各个化学成分的生物效价权重系数,进而构建了一种基于生物效价权重系数加权的多组分化学定量分析的大黄质量评控模式:致泻效应成分指数。动物实验伦理要求已获得原解放军302医院动物实验伦理委员会的批准(批准号:IACUC-2015-012)。研究结果表明,在不同基原的大黄饮片、炮制品中12个指标性化学成分含量存在较大的差异,特别值得关注的是Rh03中芦荟大黄素-8-O-β-D-葡萄糖苷的含量比Rh07中该成分的含量高近40倍(4.79 vs 0.12 mg·g-1),Rh03中大黄酸-8-O-β-D-葡萄糖苷的含量比Rh07中该成分的含量高近45倍(3.56 vs 0.08 mg·g-1)。实际测得的12个指标性化学成分的致泻生物效价范围在61.65 ±4.28~233.84 ±5.58 U·mg-1之间,差异较大。理论计算得到的16个大黄样品的效应成分指数范围在1.07(Rh15)~19.38(Rh03)之间,在小鼠便秘模型实际测得16个大黄样品的致泻生物效价范围在23.84 U·g-1(Rh16)~310.94 U·g-1(Rh05)之间。统计分析结果显示,单个化学成分含量与实际测得大黄样品的泻下通便效果的相关性比较,致泻效应成分指数与实际测得的大黄样品泻下通便效果的相关性最好(r=0.969 5),提示致泻效应成分指数可能更加适合用于评价以致泻功效为导向时大黄的质量。
关键词:    生物效价      化学成分      定量分析      整合量化      效应成分指数      质量评价      大黄     
Application of an effect-constituents index for the quality evaluation of the traditional Chinese medicine rhubarb
TAN Peng1,2, WANG Jia-bo3, ZHANG Ding-kun2, ZHOU Yong-feng3, NIU Ming3, WANG Mei4, ZHAO Jun-ning1, XIAO Xiao-he3
1. Sichuan Academy of Traditional Chinese Medicine, State Key Laboratory of Quality Evaluation of Traditional Chinese Medicine, Chengdu 610041, China;
2. College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China;
3. the Fifth Medical Center of PLA General Hospital, China Military Institute of Chinese Medicine, Beijing 100039, China;
4. LU-European Center for Chinese Medicine and Natural Compounds, Institute of Biology, Leiden University, Leiden 2333 BE, Netherlands
Abstract:
To explore the application of an effect-constituents index (ECI) for the quality evaluation of rhubarb, we carried out the simultaneous determination of 12 chemical components by ultra-performance liquid chromatography and used the ICR mouse constipation model to determine the diarrhea biopotency of these 12 components. With the diarrhea biopotency of sennoside A as a reference, the diarrhea biopotency weight coefficient of each chemical component was obtained. A multi-component chemical quantitative analysis combined with the biopotency weight coefficients for rhubarb was developed, named the diarrhea ECI. Animal experiment ethics requirements were approved by the Animal Experimental Ethics Committee of the 302 Hospital of the People's Liberation Army (Grant Number:IACUC-2015-012). The results showed that there were significant differences in the content of the 12 chemical components in different batches of processed products of rhubarb. Especially worthy of attention was the content of aloe-emodin-8-O-β-D-glucoside in sample Rh03, nearly 40-fold higher than that in Rh07 (4.79 vs 0.12 mg·g-1), and the content of rhein-8-O-β-D-glucoside in sample Rh03, nearly 45 times higher than that in Rh07 (3.56 vs 0.08 mg·g-1). The actual measured diarrhea biopotencies of the 12 chemical components ranged from 61.65 ±4.28 to 233.84 ±5.58 U·mg-1. The calculated diarrhea effect-constituents indices of 16 rhubarb samples ranged from 1.07 (Rh15) to 19.38 (Rh03), and the actual measured diarrhea biopotencies of 16 rhubarb samples based the ICR mouse constipation model ranged from 23.84 U·g-1 (Rh16) to 310.94 U·g-1 (Rh05). The correlation between the diarrhea ECIs and the actual measured diarrhea biopotencies of 16 rhubarb samples was good (r=0.969 5), suggesting that the diarrhea effect-constituents indices may be the most suitable for evaluating the quality of different rhubarbs with regard to diarrhea.
Key words:    biological potency    chemical constituent    quantitative analysis    integrated quantification    effect-constituents index    quality evaluation    rhubarb   
收稿日期: 2019-08-31
DOI: 10.16438/j.0513-4870.2019-0709
基金项目: 国家重点研发计划(2018YFC1707000);国家自然科学基金面上项目(81573676);首都卫生发展科研专项(首发2018-2-5031);四川省科技厅研究项目(2019YJ0640,18ZDYF0821);成都市科技局技术创新研发项目(2016-HM01-00312-SF).
通讯作者: 赵军宁,Tel:86-28-85231378,E-mail:zarmy@189.com;肖小河,Tel:86-10-66933322,E-mail:pharmacy302@126.com
Email: zarmy@189.com;pharmacy302@126.com
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