PMC:4561322 / 13544-21029 JSONTXT

{"target":"http://pubannotation.org/docs/sourcedb/PMC/sourceid/4561322","sourcedb":"PMC","sourceid":"4561322","source_url":"https://www.ncbi.nlm.nih.gov/pmc/4561322","text":"3.4.2. Clustering and GO Enrichment Analysis\nWith the MCL algorithm, 57, 24, 49, 29, and 85 modules were, respectively, identified from salvia miltiorrhiza, Panax notoginseng, Dalbergia odorifera, Astragalus membranaceus, and QSYQ. The modules of QSYQ are shown in Figure 2, and the others are shown in Figures S1–S4.\nThe results of functional enrichment analysis of QSYQ using BinGO are shown in Table 5, and they show that QSYQ played a pharmacodynamics with the biological processes, such as DNA metabolic process, regulation of cAMP metabolic process, lipid metabolic process, and the regulation of blood coagulation. The results of functional enrichment analysis of salvia miltiorrhiza, Panax notoginseng, Dalbergia odorifera, and Astragalus membranaceus are shown in Tables S2–S5.\n(1) Modules Related to Qi Deficiency. In TCM, Qi refers to the energy which flows within our body, to support a variety of biological functions such as movement, digesting food, and fight against diseases [43]. Qi deficiency is reflected in the lack of energy. Therefore, the regulation of energy metabolism would improve the Qi deficiency. As shown in Table 5, QSYQ participated in the amino acid metabolic process, carbohydrate metabolic process, lipid metabolic process, and cAMP metabolic process which are related to the energy metabolism and also have been demonstrated to play critical roles in cardiovascular diseases [63–66]. Among them, amino acid metabolism, carbohydrate metabolism, and lipid metabolism are the main energy source of the body.\nAmino acid metabolism (module 35) contained proteins such as GLUD2, GLUD1, and GLS. Glutamate dehydrogenase (GLUD) is an enzyme central to the glutamate and energy metabolism of the cell [67]. GLUD activity is raised in order to increase the amount of α-ketoglutarate produced, which can be used to provide energy by being used in the citric acid cycle to ultimately produce ATP. GLUD2 and GLUD1 are the GLUD's isozymes that differ in amino acid sequence but catalyze the same chemical reaction. Glutaminase (GLS) is a multifunctional enzyme involved in energy metabolism [68]. And GLS is the GLS2's isozyme, which regulates cellular energy metabolism by increasing production of glutamate and alpha-ketoglutarate and in turn results in enhanced mitochondrial respiration and ATP generation [69]. This shows that proteins in amino acid metabolism are all involved in the energy metabolism, and QSYQ can improve the Qi deficiency by regulating the amino acid metabolism.\nCarbohydrate metabolism is the basis of the body to produce energy. Carbohydrate metabolism (module 32) contained proteins such as GALK1, SORD, and DCXR. Galactokinase 1 (GALK1) is an enzyme (phosphotransferase) that facilitates the phosphorylation of α-D-galactose to galactose 1-phosphate at the expense of one molecule of ATP. Sorbitol dehydrogenase (SORD) is an enzyme in carbohydrate metabolism converting sorbitol, the sugar alcohol form of glucose, into fructose [70]. Dicarbonyl/L-xylulose reductase (DCXR) is involved in carbohydrate metabolism and glucose metabolism which is a highly conserved and phylogenetically widespread enzyme converting L-xylulose into xylitol [71]. This shows that proteins in carbohydrate metabolism make contribution to provide energy for the body by participating in carbohydrate metabolism.\nLipid metabolism (module 83) contained proteins such as ACOT8, AACS. Acyl-coenzyme A thioesterase 8 (ACOT8) is a peroxisomal thioesterase involved more in the oxidation of fatty acids which are in order to generate acetyl-CoA, the entry molecule for the citric acid cycle, the main energy supply of animals [72]. Acetoacetyl-CoA synthetase (AACS) can directly activate ketone bodies for the synthesis of physiologically important lipidic substances such as cholesterol and fatty acid [73]. So, AACS can provide basic substances for energy metabolism. This shows that proteins in lipid metabolism are all related to energy metabolism, and QSYQ can improve the Qi deficiency by regulating the lipid metabolism.\ncAMP metabolism (module 3) contained proteins such as GCG, ADCY7, and ADCYAP1. Glucagon (GCG) is a peptide hormone of cAMP metabolic process, which generally elevates the concentration of glucose in the blood by promoting gluconeogenesis and glycogenolysis [74]. Adenylate cyclase type 7 (ADCY7) is a membrane-bound adenylate cyclase that catalyses the formation of cyclic AMP from ATP [75]. ADCYAP1 is also known as pituitary adenylate cyclase-activating polypeptide (PACAP), which stimulates adenylate cyclase and subsequently increases the cAMP level and plays crucial roles in energy metabolism, including lipid metabolism [76].\nThis indicated that the QSYQ reinforced Qi efficacy by the regulation of the cAMP metabolism, amino acid metabolism, carbohydrate metabolism, and lipid metabolism. And Qi deficiency may be associate with the modules including amino acid metabolism, carbohydrate metabolism, lipid metabolism, and the cAMP metabolism.\n(2) Modules Related to Blood Stasis. Blood stasis is caused by disturbance of blood circulation and is reflected in microcirculation relating to vessel and cell function, such as blood viscosity and blood cell adhesion [77]. As shown in Table 5, QSYQ took part in the regulation of blood coagulation and cardiac muscle contraction which can promote blood circulation.\nThe regulation of blood coagulation (module 17) contained proteins such as GGCX, F2, and SERPIND1. Gamma-glutamyl carboxylase (GGCX) catalyzes the posttranslational modification of vitamin K-dependent proteins which are involved in coagulation [78]. F2 is also known as thrombin (IIa) acts as a serine protease that converts soluble fibrinogen into insoluble strands of fibrin and activation of thrombin is crucial in physiological and pathological coagulation [79]. SERPIND1, known as heparin cofactor II, is a coagulation factor which rapidly inhibits thrombin in the presence of dermatan sulfate or heparin. SERPIND1 deficiency can lead to increased thrombin generation and a hypercoagulable state [80]. This shows that proteins in this module are all involved in the blood coagulation, and QSYQ can improve the blood stasis by the regulation of blood coagulation.\nThe cardiac muscle contraction (module 30) contained proteins such as MYL2, TNNC1, and TNNI3. MYL2 is also known as myosin regulatory light chain 2, ventricular/cardiac muscle isoform (MLC-2v) which plays a key role in the regulation of cardiac muscle contraction, through its interactions with myosin [81]. TNNC1 is also known as troponin C which is a protein that resides in the troponin complex on actin thin filaments of striated muscle (cardiac) and is responsible for binding calcium to activate muscle contraction [82]. Troponin I (TNNI3) has been shown to interact with TNNC1 [83] and has been reported to have a special role in the control of cardiac contractility [84]. This shows that proteins in this module are all participated in the cardiac muscle contraction. The mechanism of QSYQ has been reported to be related to improve myocardial function [7]. So, QSYQ can promote blood circulation and hence can improve the blood stasis by regulating the cardiac muscle contraction.\nThis indicated that QSYQ improved the blood stasis through the regulation of blood coagulation and cardiac muscle contraction. And blood stasis may be associated with the modules including the regulation of blood coagulation and cardiac muscle contraction.","divisions":[{"label":"title","span":{"begin":0,"end":44}},{"label":"p","span":{"begin":45,"end":317}},{"label":"p","span":{"begin":318,"end":786}},{"label":"p","span":{"begin":787,"end":1543}},{"label":"p","span":{"begin":1543,"end":2512}},{"label":"p","span":{"begin":2513,"end":3343}},{"label":"p","span":{"begin":3344,"end":4052}},{"label":"p","span":{"begin":4053,"end":4685}},{"label":"p","span":{"begin":4686,"end":5002}},{"label":"p","span":{"begin":5003,"end":5371}},{"label":"p","span":{"begin":5371,"end":6238}},{"label":"p","span":{"begin":6239,"end":7228}}],"tracks":[]}