To Unveil The Molecular Mechanisms Of Qi And Blood Of Traditional Chinese Medicine Through Systems Biology-Based Investigation Into Si-Jun-Zi-Tang And Si-Wu-Tang Formulae

Objective To unveil potential biologic mechanisms between Qi deficiency and blood deficiency through bioinformatics approaches,which were treated by Si-Wu-Tang(SWT)and Si-Jun-Zi-Tang(SJZT),respectively.Methods Ingredients of eight herbs from SWT and SJZT were searched from TCMID database.The genes targeted by these ingredients were chosen according to their STITCH defined high confident(combined-score more than 0.7).We then performed enrichment analysis by Gene Ontology(GO)and DAVID.Enriched GO terms with p-value less than 0.01 were collected and interpreted the biological meanings through DAVID and KEGG.Then,a visualized network was constructed with ClueGO(a Cytoscape plug-in)to compare the difference pathways between SWT and SJZT formulae.Results A total of 243 genes targeted by 195 ingredients of SWT formula and 209 genes targeted by 61 ingredients of SJZT were obtained by retrieving from TCMID database.Six metabolism pathways and two environmental information processing pathways enriched by targets were correlated with two or more herbs in SWT and SJZT formula,respectively.Expect for disease associated pathways,SWT significantly influence metabolism of amino acid,carbohydrate and vitamins.Including beta-Alanine metabolism,histidine metabolism,phenylalanine metabolism,tyrosine metabolism,tryptophan metabolism,ascorbate and aldarate metabolism,pentose and glucuronate interconversions,glycolysis/gluconeogenesis,retinol metabolism.While pathways enriched by genes targeted by ingredients of SJZT mainly belonged to organismal system function,environmental information processing,metabolism and cellular processes.Including hormone secretion(Thyroid hormone,Ovarian steroidogenesis,Prolactin and Oxytocin),Bile secretion,Vascular smooth muscle contraction and Serotonergic synapse,Neuroactive ligand-receptor interaction and calcium signaling pathway,Linoleic acid metabolism and Regulation of lipolysis in adipocytes,and Gap junction.The common pathways of SWT and SJZT include Estrogen,GnRH,PPAR,GABAergic synapse,Arginine and proline metabolism,Steroid hormone biosynthesis,Metabolism of xenobiotics by cytochrome P450,cAMP,TNF and Apoptosis.Conclusion SWT plays the role of "enriching blood" by affecting the metabolism of amino acids and carbohydrates and supplementing the nutrients necessary for the human body.And it proved that the material basis of blood is closely related to amino acids and carbohydrates.SJZT plays the role of "enriching qi" by affecting the activities of neuroendocrine system;regulates the secretion of thyroid hormone,ovarian steroid hormone,prolactin and oxytocin;promotes the growth and development of human body;maintain normal body temperature;promotes the material metabolism and energy transformation,and to maintain the normal function of each viscera.Then it proved that the biological basis of qi is closely related to the neuroendocrine network.In addition,SWT and SJZT can regulate the functional activities of the hypothalamic pituitary adrenal and gonadal axis by affect inhibitory synapses(GABAergic synapse),and enhance immunity,reflecting the relationship between qi and blood.