Systems-biology dissection of mechanisms and chemical basis of herbal formula in treating chronic myocardial ischemia. (December 2016)

• Record Type: Journal Article
• Authors: Guo, Shuzhen; Li, Peng; Fu, Bangze; Chuo, Wenjing; Gao, Kuo; Zhang, Wuxia; Wang, Junyao; Chen, Jianxin; Wang, Wei
• Is Part Of: Pharmacological research. Volume 114(2016:Dec.)
• Page Start: 196
• Page End: 208
• Publication Date: 2016-12
• Subjects: QSKL qishenkeli -- TCM traditional Chinese medicine -- MI Myocardial ischemia -- HF heart failure -- ACE angiotensin-converting enzyme -- CHD coronary heart disease -- CHF chronic heart failure -- APS Astragalus propinquus Schischkin., root and rhizome -- SMB Salvia miltiorrhiza Bunge., root and rhizome -- LGT Lonicera japonica Thunb., flower -- ACD Aconitum carmichaelii Debeaux., lateral root -- GGL Glycyrrhiza glabra L., root and rhizome -- SNH Scrophularia ningpoensis Hemsl., root -- PCA Principal component analyses -- LTCCs L-type Ca2+ channels -- SERCA2a sarcoplasmic/endoplasmic reticulum calcium ATPase 2a -- RyR Ryanodine receptors -- DRM Desmin-related myopathy -- ECM extracellular matrix -- FFAs Free fatty acids -- CMap Connectivity Map -- ACEI Angiotensin-converting enzyme inhibitor -- β-AR β-adrenergic receptor -- SEA Similarity ensemble approach -- RAAS Renin–angiotensin–aldosterone system -- LCx left circumflex coronary artery -- LVIDd Left ventricular internal dimension diastole -- LVIDs Left ventricular internal dimension systole -- LEDV Left ventricular end-diastolic volume -- LESV left ventricular end-systolic volume -- EF left ventricular ejection fraction -- SV stroke volume -- FS fractional shortening -- SBP systolic blood pressure -- DBP diastolic blood pressure -- MAP mean arterial pressure -- LVESP left ventricular systolic pressure -- LVEDP left ventricular diastolic pressure -- HR heart rate -- LVET left ventricular ejection time -- BNP brain natriuretic peptide -- cTnT troponin T -- TTD Therapeutic target database -- OMIM online mendelian inheritance in man -- MM morbid map -- TCMSP traditional Chinese medicine systems pharmacology database; Herbal medicine -- Systems biology -- Transcriptome sequencing -- Chronic myocardial ischemia; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2016.10.026
• Languages: English
• ISSNs: 1043-6618

Abstract

Abstract: Herbal medicine is a mixture of multiple compounds, and is intended to exhibit therapeutic effects by attacking multiple disease-causing modules simultaneously. However, it is still a challenge for scientists to untangle the complex biological mechanisms and underlying material basis of herbal medicine. Here, this study was designed to build a systems-biology platform for exploring the molecular mechanisms and corresponding active compounds, with a typical example applied to an herbal formula Qishenkel (QSKL) in the treatment of chronic myocardial ischemia. We have applied an approach integrating transcriptome sequencing, bioactivity profiling inference, computational ligand-receptor evaluation and experimental validation to study the effects on pig myocardial ischemia treated with QSKL. Numerous biological modules were revealed and indicated the coordinated regulation of molecular networks from various aspects of cardiac function. In addition, gene expression profiles were utilized to identify a number of key therapeutic targets of herbal formula, such as angiotensin-converting enzyme and calcium channels. Then, these therapeutic targets were used to fish the potential active ingredients based on a combination of target structure-based and chemical ligand-based methods. Some active compounds, including luteolin, cryptotanshinone, licochalcone A, glycyrrhetinic acid, salsolinol, isoacid chlorogenic C, salvianolic acid A and salvianolic acid B, have been validated by direct biochemical methods. This strategy integrating different types of technologies is expected to provide not only a detailed understanding about the combined therapeutic effects of herbal mixture but also a new opportunity for discovering novel natural molecules with pharmacological activities.