This study demonstrates the feasibility of microarray technology in combination with other techniques for the evaluation of therapeutic efficiencies and mechanism studies of CHF.
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Wang et al. After evaluating the effects of signaling pathways and metabolism, the authors found that DQP can reverse energy metabolic disorders to recover cardiac function. In addition, genomics has been used to analyze therapeutic targets of CHF and to predict other potential drugs. Tang et al. Using an mRNA microarray with enrichment analysis, Wang et al.
Kim et al. Considering that molecular docking technology may lead to omitted or incorrect information, Zhang et al. It is expected that genomics or genomics combined with other omics analyses will offer comparatively high practical value with a systematic flow in the study of CHF. Transcriptomics technologies are techniques used to study gene transcription and transcriptional regulation.
Unlike the static genome, the transcriptome is regulated by both exogenous and endogenous factors. Therefore, the transcriptome is a dynamic link between the genome of a species and its external physical characteristics, reflecting the expression level of all genes in a particular organ, tissue or cell at a particular physiological stage. The current methods for obtaining and analyzing transcriptome data can be divided into two categories: targeted and untargeted methods [ 24 ]. The advantages of cDNA-AFLP technology are its repeatability, low false-positive rate and ability to detect the expression of mRNA in low abundance, while the associated difficulty is the selection of suitable endonuclease combinations [ 25 ].
Northern blotting is mainly applied to studies of the dynamic expression of specific trait genes at the mRNA level. Using in situ hybridization technology to detect the expression of miRNA can provide a more intuitive display of the spatial and temporal expression patterns of miRNA. Cui et al. The biological functions and signal transduction pathways of the differentially expressed genes were analyzed and were found to be related to hemoglobin complexes, oxygen transporters, oxygen transporters, and pyruvate metabolism.
Dai et al. EST can analyze a large sample number and can be used for cross-species comparative analysis; however, the data volume is large, and the error rate is high. SAGE is not only qualitative but also quantitative for gene differences, but one significant drawback of this technique is that it requires a large amount of mRNA. MPSS is simple and efficient and can provide information on terminal sequences, and it is suitable for any organism; however, the detection cost is high. RNA-seq with digital signaling has high sensitivity and quantitative accuracy.
The transcriptome is characterized by time specificity, tissue specificity and spatial specificity. Through the functional annotation analysis of differentially expressed genes, 26 important pathways for HLJDD inhibition of Candida albicans infection were identified, especially those occurring through DNA replication and transporter activity pathways. However, to enable the transcriptome to play a greater role in the study of CHF, more attention should be paid to the study of gene modification and protein modification to deepen the understanding of the function and structure of functional genes and regulatory genes.
Proteomics is an extension of the concept of the proteome and generally refers to the large-scale study of proteins and proteomes, including protein expression levels, post-transcriptional modifications and interactions [ 31 ]. The separation techniques in proteomics research include two-dimensional gel electrophoresis 2DGE , fluorescence two-dimensional differential gel electrophoresis 2-D DIGE , multidimensional liquid chromatography MDLC , and capillary electrophoresis CE.
Among these techniques, 2DGE is the most widely used separation technology in proteomics research. The technique can solve the problem of repeatability and reduce the human error associated with gel contrast analysis. MDLC can be directly linked to mass spectrometry MS , easily realizing automation and high throughput and avoiding limitations associated with the molecular weight and isoelectric point.
However, MDLC is not as intuitive as gel electrophoresis for visualizing protein spots, and its resolution and reproducibility are not as good as those of 2DGE.
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CE combines electrophoretic separation with chromatographic separation technology. The technique has advantages in sensitivity, separation efficiency and cost, but it is difficult to analyze proteins with high molecular weights using this approach. MALDI is suitable for detecting the molecular mass of peptide segments but not peptide sequences. ESI—MS has a shorter detection time and higher sensitivity and resolution than MALDI, but it requires higher sample purity and more complex data acquisition and analysis.
According to the occurrence and development of diseases, CHF mostly function at the protein level [ 33 ]. Proteomics research overcomes the nonlinear relationship between protein expression and genes and studies the mechanism and target of CHF action directly at the protein level.
Proteomics technology, as the main method of large-scale research on proteins, is applied mainly in two respects: to protein expression profile differences and to protein structure, function and interaction analysis. Many studies use proteomics to study the changes in protein spectrum before and after intervention of CHF and to evaluate the pharmacodynamics of CHF at the overall level.
Fan et al. In the same vein, the determination of protein expression profiles was conducted in research on the effect of the Fuzheng Huayu formula [ 36 ] and Yinchenhao decoction [ 37 ] on the proteome of fibrotic livers, as well as the effects of the ZiBu PiYin recipe [ 38 ] and Tianqi Jiangtang capsule on diabetes, of Yuanshi Shengmai Chenggu tablets on avascular osteonecrosis of the femoral head [ 39 ], of Jie-Geng-Tang on lipopolysaccharide-induced acute lung injury in mice [ 40 ], and of the Tao Hong Si Wu decoction against ischemia reperfusion injury [ 41 ]. Protein changes in the body may be the result or the cause of disease; therefore, abnormal proteins and their interactions during the disease course may be potential targets for CHF.
In research carried out by Tang et al.
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The researchers then proposed three CHFs containing these compounds for increasing the activity of MMP-9 proteins and thus reducing the side effects of tetracycline. Liu et al. Metabolomics, which emerged in the s, studies the metabolic regulatory networks of organisms by examining their metabolic products and dynamic changes in the course of diseases. Metabolomics is widely used in the study of pathophysiological changes of diseases.
By evaluating the differential expression of various endogenous substances, such as blood and urine, much information about disease diagnosis and drug efficacy can be provided [ 44 ]. NMR enables noninvasive, unbiased detection of samples and is responsive to hydrogen-containing compounds; thus, the technique can detect as many compounds as possible in a sample. However, the sensitivity of NMR is lower than that of mass spectrometry.
Wei et al. NMR-based metabolomic and pathological studies showed that Coptis chinensis and its main alkaloid, berberine, could inhibit inflammatory factors and protect the liver. It is difficult to simultaneously determine the metabolites coexisting in biological systems at very different concentrations. Analytes in metabolomics samples contain highly complex mixtures. By separating some analytes from others, complex mixtures can be simplified before testing. The separation procedure is not mandatory and is usually omitted in NMR. Because existing analytical techniques each have their own advantages and scope of application, the strategy for metabolomics comprehensive analysis is to combine separation and analytical techniques.
GC—MS is suitable for the analysis of metabolites with low molecular weights, low polarity and low boiling points or volatile substances after derivatization. Feng et al. The authors concluded that XFZY treatment can alleviate neurological impairment and cortical lesion volume on the third day after brain injury and reverse the abnormalities of plasma metabolites such as glutamate, lactic acid, 3-hydroxybutyric acid and ribitol [ 48 ]. GC-TOF—MS was used to evaluate the efficacy and mechanism of the Shenfu decoction in the treatment of chronic heart failure induced by coronary artery ligation in rats.
Unsupervised principal component analysis showed that CHF significantly altered the fingerprint of urinary metabolites. After SFD treatment, the metabolomic profiles of CHF rats were significantly reversed, and the pathways of fatty acid biosynthesis, fatty acid elongation, steroid biosynthesis, galactose metabolism and amino acid metabolism in rats were significantly altered [ 49 ]. LC—MS is suitable for the analysis of high-molecular-weight, thermally instable and high-boiling-point compounds.
Using this method, Wu et al. Yan et al. In addition, the effect and mechanism of Jinxin oral liquid in treating viral pneumonia caused by the respiratory syncytial virus via improving lipid metabolism disorders [ 52 ], the protective effect of low-dose Sini decoction against myocardial injury induced by isoproterenol [ 53 ], the inhibitory effect of the Yinchenhao decoction toward dimethylnitrosamine-induced liver fibrosis in rats [ 54 ], and the improvement from the modified Jiu Wei Qiang Huo decoction on H1N1-virus pneumonia in mice [ 55 ] have all been well verified by LC—MS technology. Regardless of which analytical technology is adopted, no single technique can completely cover all metabolomics compounds [ 56 ].
In recent years, researchers have tried to integrate various analytical techniques to give full play to the advantages of various methods. These studies suggest that appropriate analytical techniques need to be selected before metabolomics studies on CHF can be carried out so that the results can be more comprehensive and accurate.
Metabolites are not confined to the substrates and products of certain enzymes in the metabolic pathway. Instead, metabolites act as structural units, signaling molecules, and regulatory factors and play many other roles and interact in the form of a metabolic network in life activities. Metagenomics is a microbial research method based on the genome of microbial populations in environmental samples, aiming at examining microbial diversity, population structure, evolutionary relationships, functional activities, interactions and environmental relationships.
Functional gene screening and sequencing analysis are the research means. At present, the main application of metagenomics in-clinic is based on gene sequence analysis of microbial species and compositions. High-throughput, large-scale, in-depth sequencing combined with multivariate statistical methods can provide more direct information on the composition and function of microorganisms and identify specific bacterial groups closely related to the physiological and pathological state of the organism. Similarly to DGGE, TGGE can only analyze DNA fragments shorter than base pairs, and there are only ten to twenty bands in the map reflecting the dominant flora in the community, while the disadvantaged flora cannot be detected.
However, when two distinct sequences share a terminal restriction site, they cannot be distinguished and only show one peak on an electropherogram. One of the main methods for the application of metagenomics in CM research is to construct a 16S rRNA gene library for flora analysis based on the species specificity of the 16S rRNA gene. Another common method is to extract the total nucleic acid from bacteria and amplify the 16S rRNA gene by PCR, then analyze the data by molecular biology techniques such as fingerprinting combined with multivariate statistical analysis.
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To study the effect of Xiexin Tang on the distribution of intestinal flora in rats with type 2 diabetes mellitus T2DM , Wei et al. Sequencing analysis showed that certain short-chain fatty acid-producing and anti-inflammatory bacteria in the intestinal microflora of T2DM rats were significantly altered after Xiexin Tang intervention, and these microbiotas were closely related to the changes in related indices of T2DM.
Tong et al. Then, Illumina sequencing and multivariate statistical methods were used to analyze the V3 and V4 regions of 16S rRNA genes to evaluate changes in the intestinal microbial structure.
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The results suggest that the combination of metformin and CHF may improve T2DM with hyperlipidemia by enriching Brucella and fecal bacilli and other beneficial bacteria. To verify that oil tea can induce changes in intestinal microbes and play an anti-diabetic role, Lin et al. The results showed that Lachnospiraceae were significantly enriched after oil tea treatment and correlated with decrease indicators related to diabetes.
Gao et al. It appeared that S could regulate the abundance of 9 intestinal flora, while S incubated in gastric and intestinal juice enhanced the ability to regulate the composition of intestinal flora and regulated 13 types of bacteria genera to play an immunoregulatory role. The number of microorganisms in the human body is more than ten times that of body cells, and the corresponding genetic code is times the size of the human genome [ 65 ].
Most existing studies have focused on the distribution of intestinal microorganisms. We should pay more attention to the impact of intestinal microecological changes on human health and disease; that is, we should pay more attention to the functions of microorganisms. There is a great challenge and opportunity in the deeper and wider application of metagenomics in CHF research to connect the functional changes of intestinal flora with the influence of CHF on microflora. Considering that the combination of multiple omics methods will enable the comprehensive evaluation of the efficacy and complex mechanisms of CHF, Du et al.
Their work successfully revealed the mechanism of multiple pathways regulating the cardioprotective effects of the Baoyuan decoction.
Huang et al. In their work, metabolic profiling was analyzed by LC—MS, and the correlation between biomarkers and biochemical indicators was also analyzed. Meanwhile, peripheral blood mononuclear cells were isolated, and their transcript levels were quantified by RT-PCR. The findings suggested that SFZYD regulated the MAPK pathway and thus improved the metabolic profiles and biochemical parameters in cold-stagnation and blood-stasis primary dysmenorrhea rats.
Sun et al. According to their constitutional types, subjects were divided into qi-deficiency, yin-deficiency and blood-stasis groups. Zhao et al. The team found that the higher the restored abundance and diversity of these bacteria were, the lower the reduction of HbA1c became, and they established a statistical model to predict the efficacy of these key early bacterial changes.
Clinically effective CHF usually exerts therapeutic effects by regulating multiple targets and affecting multiple pathways. At present, the evaluation system for the clinical efficacy of CHF still needs to be improved. It is difficult to explain the efficacy of CHF systematically and comprehensively by traditional evaluation methods that only use a single index or a few indices.
The evaluation of CHF efficacy combined with the integrity and dynamics of systems biology should still be based on CM syndrome differentiation and treatment concepts. In studies of the mechanisms of CHF, in addition to reflecting the pharmacodynamic substance basis of CHF from the aspects of genes, proteins, and metabolites, the bioinformatics method should be used to integrate and construct a biological network map of the mechanism of the CHF therapeutic effects and to clarify the mechanism of CHF therapeutic effects from the perspective of the organism as a whole to replace the study of pharmacodynamic mechanisms from only the molecular perspective.
Compared with traditional research techniques, the acquisition and analysis of high-throughput, large-scale data makes the research of systems biology better aligned with the characteristics of CHF. Determining how to carry out system dynamics research of CHF and combine traditional pharmacodynamic and pharmacokinetic methods to assess CHF efficacies and mechanisms remains a big challenge for future research and applications.
Although each omics method exists independently, it reflects biological characteristics from different angles. In specific studies, we should select methods and techniques according to the research objects and purposes. The study of CHF by a single omics method is usually not sufficiently comprehensive. Findings should be mutually validated in combination with multiple -omics methods, and even multicenter, multilevel research strategies should be used to identify changes in gene-protein-metabolite level consistency.
With the powerful tool of systems biology, CM can rapidly promote the development of personalized medicine. Biomed Chromatogr. Optimization of Huang-Lian-Jie-Du-decoction for ischemic stroke treatment and mechanistic study by metabolomic profiling and network analysis. Front Pharmacol. Mol BioSyst. Glaser P, Boone C. Beyond the genome: from genomics to systems biology.
Curr Opin Microbiol. Blood and urinary metabolomic evidence validating traditional Chinese medicine diagnostic classification of major depressive disorder. Chin Med. Lee S. Systems biology—a pivotal research methodology for understanding the mechanisms of traditional medicine. J Pharmacopunct. Application of metabolomics in toxicity evaluation of traditional Chinese medicines. Metabonomic study of the protective effect of Fukeqianjin formula on multi-pathogen induced pelvic inflammatory disease in rats.
Calycosin orchestrates osteogenesis of Danggui Buxue Tang in cultured osteoblasts: evaluating the mechanism of action by omics and chemical knock-out methodologies.
A network pharmacology approach to explore the mechanisms of Erxian decoction in polycystic ovary syndrome. Gupta A, Rawlings JB. Comparison of parameter estimation methods in stochastic chemical kinetic models: examples in systems biology. AIChE J. Hudson KL. Genomics, health care, and society. N Engl J Med. Leveraging GWAS for complex traits to detect signatures of natural selection in humans.
Thus, herbal products should be continually researched as the basis for development of both high quality dietary supplements and new medicines. This book intends to address some of current developments in herbal research. Convert currency. Add to Basket.
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