AUTHOR=Liu Xingkai , Chen Qian , Ji Xuming , Yu Wanchen , Wang Tong , Han Juanjuan , Li Shumu , Liu Jianan , Zeng Fangang , Zhao Yao , Zhang Yanyan , Luo Qun , Wang Shijun , Wang Fuyi 

TITLE=Astragaloside IV promotes pharmacological effect of Descurainia sophia seeds on isoproterenol-induced cardiomyopathy in rats by synergistically modulating the myosin motor

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.939483

DOI=10.3389/fphar.2022.939483

ISSN=1663-9812

ABSTRACT=Semen Lepidii (SL), Astragalus Membranaceous (AM), and their formula are widely used to treat heart failure caused by various cardiac diseases in traditional Chinese medicine practice. However, the molecular mechanism of action of SL and AM has not been completely understood. Herein, we firstly used mass spectrometry coupled to UPLC to characterize the chemical components of SL and AM decoctions, then applied MS-based quantitative proteomic analysis to profile protein expression in the heart of rats with isoproterenol-induced cardiomyopathy (ISO-iCM) before and after treated with SL alone or combined with AM, astragaloside IV (AS4), calycosin-7-glucoside (C7G) and astragalus polysaccharides (APS). We demonstrated for the first time that SL decoction alone could reverse the most of differentially expressed proteins in the heart of the rats with ISO-iCM, including the commonly recognized biomarkers natriuretic peptides (NPPA) of cardiomyopathy and sarcomeric myosin light chain 4 (MYL4), relieving ISO-iCM in rats, but AM did not pronouncedly improve the therapeutic efficiency of SL. Significantly, we revealed that AS4 remarkably promoted the therapeutic potency of SL by complementarily reversing myosin motor MYH6/7, and further downregulating NPPA and MYL4. In contrast, APS reduced the efficiency of DS due to upregulating NPPA and MYL4. These findings not only provide novel insights to better understanding and improving the combination therapeutic principle of traditional Chinese medicine, but also highlight the power of mass spectrometric proteomics strategy combined with conventional pathological approaches for the traditional medicine research.