Systems-biology dissection of mechanisms and chemical basis of herbal formula in treating chronic myocardial ischemia.
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.
Beijing University of Chinese Medicine, Chao Yang District, Beijing, 100029, PR China.
Shuzhen
S
Guo
ShanXi Agricultural University, Taigu, ShanXi Province, 030801, PR China.
Peng
P
Li
Beijing University of Chinese Medicine, Chao Yang District, Beijing, 100029, PR China.
Bangze
B
Fu
Beijing University of Chinese Medicine, Chao Yang District, Beijing, 100029, PR China.
Wenjing
W
Chuo
Beijing University of Chinese Medicine, Chao Yang District, Beijing, 100029, PR China.
Kuo
K
Gao
ShanXi Agricultural University, Taigu, ShanXi Province, 030801, PR China.
Wuxia
W
Zhang
Beijing University of Chinese Medicine, Chao Yang District, Beijing, 100029, PR China.
Junyao
J
Wang
Beijing University of Chinese Medicine, Chao Yang District, Beijing, 100029, PR China. Electronic address: Cjx@bucm.edu.cn.
Jianxin
J
Chen
Beijing University of Chinese Medicine, Chao Yang District, Beijing, 100029, PR China. Electronic address: Wangwei@bucm.edu.cn.
Wei
W
Wang
D000818:Animals; D016466:CHO Cells; D003412:Cricetulus; D055808:Drug Discovery; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010946:Plants, Medicinal / Q000737:chemistry; D013552:Swine; D049490:Systems Biology; D059467:Transcriptome / Q000187:drug effects
D004365:Drugs, Chinese Herbal
Chronic myocardial ischemia; Herbal medicine; Systems biology; Transcriptome sequencing