摘要
为探讨附子甘草药对在正常生理状态与病理状态下的核心配伍内涵,对比研究附子单煎液、附子甘草合煎液对正常大鼠与心力衰竭模型大鼠血清/心肌组织生化指标、心肌组织病理学形态以及血清代谢轮廓的影响,利用网络药理学与代谢组学关联分析,构建甘草对附子增效、减毒的代谢物-靶点-通路关联网络,并采用Western blot方法对网络中的代表性通路进行实验验证。结果显示,附子单煎液与附子甘草合煎液均可降低模型大鼠体内肌酸激酶等指标的含量,改善心肌病理损伤,同时也均可使正常大鼠体内肌酸激酶等指标含量异常升高,导致心肌病理损伤,在正常大鼠与模型大鼠组间表现出配伍减毒与配伍增效2种结果;代谢组学结果显示,与附子单煎液相比,附子甘草合煎液回调模型大鼠体内代谢物种类更多,且回调作用更优,同时干扰正常大鼠代谢物水平的作用弱于附子单煎液;关联分析结果显示,甘草增强附子抗心力衰竭药效网络共涉及112个代谢物,89个靶点,15条通路,包括钙离子信号通路、cAMP信号通路等;甘草降低附子心脏毒性网络共涉及36个代谢物,59个靶点,11条通路,包括心肌细胞肾上腺素能信号、三羧酸循环等,相关蛋白表达水平的实验结果验证了关联分析的可靠性。该文通过研究说明,附子甘草药对在生理与病理状态下的核心配伍内涵发生改变,同时其配伍增效与配伍减毒结果是基于不同代谢途径与生物通路得以实现。
This study aims to explore the core connotation of the compatibility of Aconiti Lateralis Radix Praeparata(Fuzi)-Glycyrrhizae Radix et Rhizoma(Gancao)herb pair under physiological and pathological conditions.The biochemical indicators of serum/myocardial tissue,pathological changes of the myocardial tissue,and serum metabolic profiles of normal rats and heart failure model rats treated with Fuzi Decoction and Fuzi Gancao Decoction were determined.Network pharmacology and metabolomics were employed to establish the metabolite-target-pathway network for Glycyrrhizae Radix et Rhizoma in enhancing the efficacy and reducing the toxicity of Aconiti Lateralis Radix Praeparata,Western blotting was employed to verify the representative pathways in the network.The results showed that both decoctions lowered the levels of creatine kinase and other indicators and mitigate myocardial pathological injury in model rats.However,they caused the abnormal rises in creatine kinase and other indicators and myocardial pathological injury in normal rats.The results indicated that the compatibility reduced the toxicity in normal rats and enhanced the efficacy in model rats.The results of metabolomics showed that Fuzi Gancao Decoction recovered more metabolites in model rats and had weaker effect on interfe-ring with the metabolites in normal rats than Fuzi Decoction.The association analysis showed that the network of Glycyrrhizae Radix et Rhizoma enhancing the efficacy of Aconiti Lateralis Radix Praeparata involved 112 metabolites,89 targets,and 15 pathways,including calcium and cAMP signaling pathways.The network of Glycyrrhizae Radix et Rhizoma reducing the cardiotoxicity of Aconiti Lateralis Radix Praeparata involved 36 metabolites,59 targets,and 11 pathways,including adrenergic signaling and tricarboxylic acid cycle in cardiomyocytes.The experimental results of protein expression verified the reliability of the association analysis.This study demonstrated that the core connotation of the herb pair of Aconiti Lateralis Radix Praeparata-Glycyrrhizae Radix et Rhizoma changed under physiological and pathological states,and the compatibility results of enhancing efficacy and reducing toxicity were achieved with different metabolic pathways and biological processes.
作者
彭伟
王潇
傅舒
吴明权
傅超美
涂禾
PENG Wei;WANG Xiao;FU Shu;WU Ming-quan;FU Chao-mei;TU He(School of Pharmacy,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China;Chinese Medicine Laboratory,Sichuan Provincial Orthopedic Hospital,Chengdu 610041,China)
出处
《中国中药杂志》
CAS
CSCD
北大核心
2023年第14期3793-3805,共13页
China Journal of Chinese Materia Medica
基金
国家自然科学基金项目(81603536)。
关键词
附子
甘草
配伍
代谢组学
网络药理学
Aconiti Lateralis Radix Praeparata
Glycyrrhizae Radix et Rhizoma
compatibility
metabolomics
network pharmacology
作者简介
彭伟,主管中药师,博士研究生,研究方向为中药新制剂与新剂型,E-mail:934405448@qq.com;通信作者:傅超美,教授,研究方向为中药新制剂与新剂型,E-mail:chaomeifu@126.com;通信作者:涂禾,主任中药师,研究方向为医疗机构中药制剂开发,E-mail:297983480@qq.com。
