葛根芩连汤成分间自组装纳米粒改善伊立替康所致肠毒性作用研究  

Improvement of irinotecan-induced enterotoxicity by self-assembled nanoparticles between components of Gegen Qinlian Decoction

作　　者：吴淑洋 杨晓琴 成威键 李敏[1] 李楠[1] 章津铭[1] 吴亿晗 WU Shuyang;YANG Xiaoqin;CHENG Weijian;LI Min;LI Nan;ZHANG Jinming;WU Yihan(Key Laboratory of Standardization of Chinese Materia Medica,Ministry of Education,State Key Laboratory of Southwest Specialty Chinese Medicine Resources,College of Pharmacy,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China)

机构地区：[1]成都中医药大学药学院,西南特色中药资源国家重点实验室,中药材标准化教育部重点实验室,四川成都611137

出　　处：《中草药》2024年第12期3987-3997,共11页Chinese Traditional and Herbal Drugs

基　　金：国家中医药管理局中医药创新团队及人才支持项目(ZYYCXTD-D-202209);国家资助博士后研究人员计划项目C档(GZC20230335)。

摘　　要：目的基于中药经典复方葛根芩连汤(Gegen Qinlian decoction,GQD)合煎过程中成分间相互作用,探讨其代表性成分葛根素、小檗碱、汉黄芩苷、黄芩苷、甘草酸、巴马汀体外结合形成自组装纳米粒的性能及改善伊立替康(CPT-11)所致肠毒性作用的药理活性,为来源于中药汤剂的活性成分间的自组装纳米粒提供参考。方法采用溶剂挥发法分别制备小檗碱-汉黄芩苷自组装纳米粒(berberine-wogonoside nanoparticles,Ber-Wog NPs)、小檗碱-葛根素自组装纳米粒(berberine-puerarin nanoparticles,Ber-Pue NPs)、黄芩苷-葛根素自组装纳米粒(baicalin-puerarin nanoparticles,Bai-Pue NPs)、黄芩苷-巴马汀自组装纳米粒(baicalin-palmatine nanoparticles,Bai-Pal NPs)、黄芩苷-甘草酸自组装纳米粒(baicalin-glycyrrhizic acid nanoparticles,Bai-GA NPs)5种组分自组装纳米粒,测定其粒径分布、多分散指数(polydispersity index,PDI)、包封率、载药量,采用透射电子显微镜(transmission electron microscope,TEM)观察其微观形貌,紫外光谱和傅里叶红外光谱考察成分间相互作用;考察5种组分自组装纳米粒缓解CPT-11致小鼠迟发性腹泻的药理作用。结果组分间按1∶1投药比,制备所得Ber-Wog NPs、Ber-Pue NPs、Bai-Pue NPs、Bai-Pal NPs、Bai-GA NPs的平均粒径分别为(198.09±4.64)、(216.29±5.31)、(173.53±5.46)、(185.75±3.38)、(242.10±12.30)nm;PDI分别为0.14±0.06、0.13±0.06、0.19±0.03、0.19±0.01、0.21±0.05,TEM观察均为球状纳米粒,除Ber-Wog NPs外,其余4种纳米粒包封率均较高。紫外可见吸收光谱和红外光谱提示,5种纳米粒的组装均是通过分子间非共价键作用形成;分子对接模型进一步提示,其形成机制与分子间静电相互作用或氢键相关。药效试验结果显示,制剂组可缓解小鼠体质量降低,腹泻指数降低,结肠组织炎症因子肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-1β(interleukin,IL-1β)含量降低,IL-1Objective Based on the interactions among the components in the combined decoction process of the classical Chinese medicine compound Gegen Qinlian Decoction(葛根芩连汤,GQD),we investigated the performance of its representative components,puerarin,berberine,baicalin,baicalin,glycyrrhizic acid,and pamadine,in combining with each other in vitro to form self-assembled nanoparticles,and their pharmacological activities in ameliorating the enterotoxicity effects induced by irinotecan(CPT-11),so as to provide references for self-assembled nanoparticles among active ingredients originating from the traditional Chinese medicine broths.Methods The five self-assembled berberine-wogonoside nanoparticles(Ber-Wog NPs),berberine-puerarin nanoparticles(Ber-Pue NPs),baicalin-puerarin nanoparticles(Bai-Pue NPs),baicalin-palmatine nanoparticles(Bai-Pal NPs),and baicalin-glycyrrhizic acid nanoparticles(Bai-GA NPs)were prepared by solvent evaporation method.Then,the particle size,polydispersity index(PDI),drug entrapment efficiency and drug loading efficiency of the nanoparticles were measured.The morphology was observed by transmission electron microscopy,and the interaction between the components was investigated by the UV-vis absorption spectroscopy and Fourier transform infrared spectroscopy.In addition,the pharmacological effects of five self-assembled nanoparticles on alleviating delayed diarrheam mice model induced by irinotecan(CPT-11)in mice were investigated.Results The average particle size of Ber-Wog NPs,Ber-Pue NPs,Bai-Pue NPs,Bai-Pal NPs,Bai-GA NPs were(198.09±4.64),(216.29±5.31),(173.53±5.46),(185.75±3.38),(242.10±12.30)nm,respectively.The average PDI was 0.14±0.06,0.13±0.06,0.19±0.03,0.19±0.01,0.21±0.05,respectively.Furthermore,the five self-assembled nanoparticles were spheroidal nanoparticles observed by transmission electron microscopy.The other four nanoparticles have higher encapsulation efficiency except Ber-Wog NPs.The UV-vis absorption spectroscopy and Fourier transform infrared spectroscopy su

关 键 词：葛根芩连汤 自组装 纳米粒 肠毒性 成分互作 葛根素 小檗碱 汉黄芩苷 黄芩苷 甘草酸 巴马汀 溶剂挥发法 腹泻 

分 类 号：R283.6[医药卫生—中药学]