地黄宝源颗粒治疗糖尿病药效评价及基于UHPLC-LTQ-Orbitrap MS的成分分析和体内分布  

Evaluation of efficacy of Dihuang Baoyuan Granules for diabetes mellitus and composition and in vivo distribution analysis based on UHPLC-LTQ-Orbitrap MS

作　　者：田孟尧 王梦晓 罗珂珂 胡天宝 李洪梅[1] 霍姝含 郝莉雨 司南[1] 高文雅 刘玉洋 边宝林[1] 王宏洁[1] 周严严[1] TIAN Meng-yao;WANG Meng-xiao;LUO Ke-ke;HU Tian-bao;LI Hong-mei;HUO Shu-han;HAO Li-yu;SI Nan;GAO Wen-ya;LIU Yu-yang;BIAN Bao-lin;WANG Hong-jie;ZHOU Yan-yan(Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China;Beijing Supreme Life Co.,Ltd.,Beijing 100176,China)

机构地区：[1]中国中医科学院中药研究所,北京100700 [2]北京精医和生医药科技有限公司,北京100176

出　　处：《中国中药杂志》2024年第10期2783-2797,共15页China Journal of Chinese Materia Medica

基　　金：胡天宝基层老中医传承工作室项目(2020-JC-02)。

摘　　要：地黄宝源颗粒是北京名老中医胡天宝使用并推荐治疗2型糖尿病的处方,目前已证实该方临床疗效确切。此方由7味药组成,化学组成较为复杂。该研究旨在开展地黄宝源颗粒化学成分分析,评价其治疗糖尿病药效并分析给药后血浆、肝脏、肾脏成分分布,为其药效物质研究提供参考依据。研究采用UHPLC-LTQ-Orbitrap MS对地黄宝源颗粒的主要化学成分进行分析,色谱分离采用Waters ACQUITY Premier HSS T3色谱柱(2.1 mm×100 mm,1.8μm),流动相为0.1%甲酸水(A)-乙腈(B),梯度洗脱,流速0.3 mL·min^(-1);采用电喷雾离子源(ESI)在正、负离子模式下采集数据。在此基础上,糖尿病大鼠造模方法采用高糖高脂饲料喂养和腹腔注射链脲佐菌素(streptozocin,STZ) 35 mg·kg^(-1),给予地黄宝源颗粒后对空腹血糖、糖化血红蛋白等指标进行药效学评价,并对给药后血浆、肝脏及肾脏中的成分进行鉴定。根据准分子离子与二级碎片离子,结合对照品质谱特征及文献报道,从地黄宝源颗粒中共鉴定了191个成分,包括29个生物碱类,24个黄酮类,22个有机酸类,16个氨基酸类,13个环烯醚萜类,11个甾体皂苷类,9个糖类,8个苯乙醇苷类,8个核苷类,2个苯丙素类,49个其他类成分。灌胃给药后,在大鼠血浆、肝脏、肾脏中分别鉴定出83、109、98个化学成分。通过对地黄宝源颗粒化学成分鉴定及大鼠给药后体内成分分析,为后续地黄宝源颗粒的药效物质基础研究及进一步的临床应用提供科学依据。Dihuang Baoyuan Granules is a prescription endorsed by HU Tianbao,a renowned and elderly Chinese medicine practitioner from Beijing,and has demonstrated definite clinical efficacy.The composition of this prescription is intricate as it includes 7 distinct herbal medicines.This study aims to analyze the chemical composition of Dihuang Baoyuan Granules,evaluate its efficacy in the treatment of diabetes and analyze the distribution of the drug components in the plasma,liver,and kidney after administration.The findings will serve as a reference for future research on pharmacodynamic substances of this prescription.UHPLC-LTQ-Orbitrap MS was employed to analyze the main chemical components of Dihuang Baoyuan Granules.A Waters ACQUITY Premier HSS T3 column(2.1 mm×100 mm,1.8 μm) was used for chromatographic separation with 0.1% formic acid(A)-acetonitrile(B) as the mobile phases in a gradient elution at a flow rate of 0.3 mL·min~(-1).Electrospray ionization(ESI) source was used to acquire data in positive and negative ion modes.Furthermore,a rat model of diabetes mellitus was established by feeding with a high-sugar high-fat diet,and injection with streptozocin at a dose of 35 mg·kg~(-1),and the modeled rats were then administrated with Dihuang Baoyuan Granules.The fasting blood glucose,hemoglobin A1c,and other relevant indicators were measured,and the substances present in the plasma,liver,and kidney were identified.By reference to quasi-molecular ions,MS/MS fragment ions,MS spectra of reference substances,and compound information in available reports,191 components were identified in Dihuang Baoyuan Granules,including 29 alkaloids,24 flavonoids,22 organic acids,16 amino acids,12 terpenes,11 steroid saponins,9 sugars,8 phenylethanoid glycosides,8 nucleosides,2 phenylpropanoids,and 49 others compounds.Eighty-three chemical components were identified in rat plasma,109 in the liver,and 98 in the kidney.Component identification and characterization of Dihuang Baoyuan Granules in vitro and in vivo provide efficacy inform

关 键 词：地黄宝源颗粒 糖尿病 UHPLC-LTQ-Orbitrap MS 成分鉴定 入血成分 组织分布 

分 类 号：R285.5[医药卫生—中药学]