药学学报, 2021, 56(9): 2561-2566
引用本文:
杨玉琴#, 李菲菲#, 陈珊, 王志家, 王鹏龙*, 雷海民*. 基于甘草酸增溶原理探讨中药芫花与甘草配伍增毒机制[J]. 药学学报, 2021, 56(9): 2561-2566.
YANG Yu-qin#, LI Fei-fei#, CHEN Shan, WANG Zhi-jia, WANG Peng-long*, LEI Hai-min*. The mechanism of toxicity enhancement with the combination of Flos Genkwa and Radix et Rhizoma Glycyrrhizae based on the solubilization of glycyrrhizic acid[J]. Acta Pharmaceutica Sinica, 2021, 56(9): 2561-2566.

基于甘草酸增溶原理探讨中药芫花与甘草配伍增毒机制
杨玉琴#, 李菲菲#, 陈珊, 王志家, 王鹏龙*, 雷海民*
北京中医药大学中药学院, 北京 102488
摘要:
为了研究芫花-甘草配伍禁忌,本文探索了其增溶增毒本质。本实验采用色谱、场发射扫描电子显微镜、MTT细胞毒性评价等方法研究芫花乙酸乙酯部位单煎及其与甘草酸共煎的主要化学成分、形貌学和毒性变化,以期明确芫花-甘草配伍禁忌的本质,为芫花-甘草配伍禁忌的研究提供新思路。结果显示,通过高效液相色谱法(high performance liquid chromatography,HPLC)检测,芫花乙酸乙酯部位与甘草酸共煎煮后的毒性成分芫花酯甲的溶出量达54.8%,而单煎的芫花乙酸乙酯部位则未检测到芫花酯甲色谱峰;通过扫描电子显微镜观测发现,共煎煮溶出率增加的原因是由于甘草酸将芫花脂溶性成分均匀分散成纳米级颗粒,在溶液中溶解性和稳定性提高。进一步的细胞毒性评价结果显示,共煎煮后细胞存活率降低,4',6-二脒基-2-苯基吲哚(4',6-diamidino-2-phenylindole,DAPI)染色也得到同样结果。综上,芫花乙酸乙酯部位与甘草酸共煎煮后促进毒性成分芫花酯甲的溶出,并使该部位形成分布均一的纳米颗粒,有利于成分吸收,从而致毒性增强。
关键词:    芫花      甘草      配伍禁忌      甘草酸      芫花酯甲     
The mechanism of toxicity enhancement with the combination of Flos Genkwa and Radix et Rhizoma Glycyrrhizae based on the solubilization of glycyrrhizic acid
YANG Yu-qin#, LI Fei-fei#, CHEN Shan, WANG Zhi-jia, WANG Peng-long*, LEI Hai-min*
School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 102488, China
Abstract:
In order to study the contraindications of the compatibility of Flos Genkwa-Radix et Rhizoma Glycyrrhizae, in this study, the solubilizing and poisoning essence were explored. In this experiment, chromatographic assay, field emission scanning electron microscopy, MTT cytotoxicity evaluation, and other methods were used to study the main chemical components, morphology and toxicity of the ethyl acetate part of Flos Genkwa and its co-decoction with glycyrrhizic acid, in order to clarify Flos Genkwa-Radix et Rhizoma Glycyrrhizae incompatibility provides a new idea for the research on incompatibility of Flos Genkwa-Radix et Rhizoma Glycyrrhizae. The results showed that after co-decoction of the ethyl acetate part of Flos Genkwa with glycyrrhizic acid, high performance liquid chromatography (HPLC) detected the dissolution of the toxic component yuanhuacine of 54.8%, while yuanhuacine chromatographic peak was not detected in the Flos Genkwa ethyl acetate part of the single decoction. The increase of co-decoction dissolution rate was observed by scanning electron microscopy, and it was found that glycyrrhizic acid uniformly dispersed the fat-soluble components of Flos Genkwa into nano-scale particles, which improved the solubility and stability in the solution. Furthermore, the results of cytotoxicity evaluation showed that the survival rate of cells decreased after co-decoction, 4',6-diamidino-2-phenylindole (DAPI) staining also gave the same results. In summary, the co-decoction of the ethyl acetate part of Flos Genkwa with glycyrrhizic acid promotes the dissolution of the toxic component yuanhuacine, and makes the part form uniformly distributed nanoparticles, which is conducive to the absorption of the ingredient and increases the toxicity.
Key words:    Flos Genkwa    Radix et Rhizoma Glycyrrhizae    incompatibility    glycyrrhizic acid    yuanhuacine   
收稿日期: 2021-04-06
DOI: 10.16438/j.0513-4870.2021-0495
基金项目: 国家自然科学基金资助项目(81903816,82073974);中央高校基本科研业务费(青年教师项目:2019-JYB-JS-018;岐黄团队项目:2019-JYB-TD005);北京市科技新星计划(Z201100006820026);中华中医药学会青年人才托举工程项目(CACM-2018-QNRC2-B08);北京中医药大学重点攻关项目(2020-JYB-ZDGG-044);北京市中药基础与新药研究重点实验室.
通讯作者: 王鹏龙,Tel:86-10-53912100,E-mail:wpl581@126.com;雷海民,E-mail:hm_lei@126.com
Email: wpl581@126.com;hm_lei@126.com
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参考文献:
[1] Ou LN, Zhong GS, Liu HY, et al. Historical evolution, incompatibility arguments and suggestions on "eighteen incompatible medicaments"[J]. Sci Technol Rev (科技导报), 2015, 33:88-94.
[2] Xiu LL, Zhong GS, Zhang JM, et al. Review on the experimental studies of suitable and contraindicant conditions of Chinese medicine antagonism compatibility genkwa flos and glycyrrhiza[J]. Glob Tradit Chin Med (环球中医药), 2015, 8:1050-1053.
[3] Shen J, Mo X, Tang Y, et al. Analysis of herb-herb interaction when decocting together by using ultra-high-performance liquid chromatography-tandem mass spectrometry and fuzzy chemical identification strategy with poly-proportion design[J]. J Chromatogr A, 2013, 1297:168-178.
[4] Chen YY, Qian DW, Shang EX, et al. The incompatibility mechanism based on the interaction of multiple components for Flos Genkwa and Radix et Rhizoma Glycyrrhizae[J]. Acta Pharm Sin (药学学报), 2012, 47:1043-1048.
[5] Dai GX. Experimental study on toxicity and efficacy of genkwa flos stir-baked with vinegar[J]. Chin Arch Tradit Chin Med (中华中医药学刊), 2012, 30:2766-2767.
[6] Li FF. Studies on Bioactive Constituents of Two Plants from the Genus Daphne (两种瑞香属植物芫花和黄瑞香的活性成分研究)[D]. Shenyang:Shenyang Pharmaceutical University, 2013.
[7] Xu ZF, Li RR, Gong QF, et al. Content comparison of genkwanin and yuanhuacine in different medicinal parts of Daphne genkwa Sieb et Zucc[J]. Chin J Inf Tradit Chin Med (中国中医药信息杂志), 2011, 18:59-61.
[8] Hu JP, Li YH, Shi XC, et al. An U-2 OS cells/CCK-8 method for oncolytic activity determination of herpes simplex virus type 1[J]. Chin J Pharm Anal (药物分析杂志), 2020, 40:31-36.
[9] Lin Y, Xiao R, Yin LZ, et al. Developing spectrum-toxicity relationship with rough set theory for hepatotoxicity material basis of Polygonum multiflorum[J]. China J Chin Mater Med (中国中药杂志), 2019, 44:509-517.
[10] BalaKumaran MD, Ramachandran R, Balashanmugam P, et al. Comparative analysis of antifungal, antioxidant and cytotoxic activities of mycosynthesized silver nanoparticles and gold nanoparticles[J]. Mater Technol, 2020. DOI:10.1080/10667857. 2020.1854518.
[11] Zhi KK. Discovery and Formation of Novel Small Molecule Natural Product Gels and Their Application in Drug Delivery (新型小分子天然产物凝胶的发现与形成及其药物传输应用)[D]. Harbin:Harbin Institute of Technology, 2019.
[12] Wei XH. Salicylic acid-grafted chitosan oligosaccharide nanoparticle for paclitaxel delivery[J]. J Bioact Compat Polym, 2010, 25:319-335.
[13] Li T, Wang PL, Guo WB, et al. Natural berberine-based Chinese herb medicine assembled nanostructures with modified antibacterial application[J]. ACS Nano, 2019, 13:6770-6781.
[14] Huang XM, Wang PL, Li T, et al. Self-assemblies based on traditional medicine berberine and cinnamic acid for adhesion-induced inhibition multidrug-resistant staphylococcus aureus[J]. ACS Appl Mater Interfaces, 2020, 12:227-237.
[15] Tian X, Wang P, Li T, et al. Self-assembled natural phytochemicals for synergistically antibacterial application from the enlightenment of traditional Chinese medicine combination[J]. Acta Pharm Sin B, 2020, 10:1784-1795.
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