Study On The Common Biomarkers Of Glucolipid Metabolic Disorders And The Mechanism Of Tianhuang Formula On Treating Hyperlipidemia

Background:The innovative theory of “Glucolipid Metabolic Disorders(GLMD)” was first proposed by Professor Jiao Guo,which is a summarization for a series of complicated diseases characterized by disorders of glucose and lipid metabolism,and proposed a comprehensive integrated therapeutic strategy.The theory breaks through the limitations of traditional concept of “one disease,one treatment”,emphasizing the common pathomechanism of a series of diseases caused by disorders of glucose and lipid metabolism.Under the guidance of the comprehensive integrated therapeutic strategy,Professor Guo has developed a variety of traditional Chinese medicine formula for treating GLMD.The preliminary basic research has proved that it has excellent lipid-lowering effects.In order to deepen the understanding of the innovative concept of "GLMD" and enrich its scientific connotation,this study intends to throw light on the single disease caused by disorders of glucose and lipid metabolism,to study its common biomarkers.Besides,systematically study the mechanism of traditional Chinese medicine formula on treating GLMD.Objective:Discover the common biomarkers of GLMD;study the mechanism of Tianhuang formula on treating hyperlipidemia systematically.Methods:1.Predict and verify the common biomarkers of GLMD through network biological methods and molecular biological methods.2.Study the mechanism of Tianhuang formula on treating hyperlipidemia via network pharmacology,metabolomics and metagenomics.Results:1.There are several common pathogenic genes in GLMD,and genes such as ALB,APOE,NOS3,SERPINE1 can be verified as common biomarkers on GLMD.2.Network pharmacology results show that Tianhuang formula on treating hyperlipidemia mainly through the regulation of insulin resistance,PPAR signaling pathway,AMPK signaling pathway,PI3K-Akt signaling pathway,etc.3.Metabolomics results show that Tianhuang formula regulates glucose and lipid abnormalities mainly through lipid metabolism.4.The results of metagenomics indicated that the intestinal microflora is one of the important targets of Tianhuang formula on treating hyperlipidemia.Tianhuang formula mainly achieved the reduction of the proportion of Bacteroides/Thickwall bacteria in the intestine of mice induced by high-fat diet.The pharmacodynamic effect mainly affects biological processes of glucose metabolism,energy metabolism,lipid metabolism,nucleotide metabolism,polysaccharide biosynthesis and metabolism.Conclusion:In this study,the common pathogenic genes of GLMD were discovered by network biology and molecular biology techniques,some common biomarkers such as ALB,APOE,NOS3,and SERPINE1 were verified.Tianhuang formula mainly affects lipid metabolism and energy metabolism through PPAR signaling pathway,AMPK signaling pathway and insulin signaling pathway.Through PI3K-Akt signaling pathway,AMPK signaling pathway and insulin signaling pathway regulate glucose metabolism and polysaccharide biosynthesis metabolism;and PI3K-Akt signal pathway pathway affects nucleotide metabolism.Besides,in addition to some key enzymes and receptors,the intestinal flora can be one of the important targets of Tianhuang formula to regulate metabolic pathways.