Study on the mechanism of action of Siheifang on zebrafish melanin based on metabolomics and network pharmacology
AIM:To study the mechanism of Sihei-fang(SHF)in improving pigment deficiency disease(PD)by combining network pharmacology and me-tabolomics.METHODS:Using zebrafish embryos with pigment deficiency disease induced by 1-phe-nyl-2-thiourea(PTU)as an animal model,the ef-fects of SHF extract(0.01,0.02,0.04 mg/mL)on the morphology,melanin area,tyrosinase activity,and melanin content of zebrafish embryos were an-alyzed.Ultra high performance liquid chromatogra-phy-mass spectrometry(UHPLC-MS)was used to screen differential metabolites and obtain relevant metabolic pathways in the SHF treatment of mela-nin deficient zebrafish embryos model.Network pharmacology was used to obtain key targets for SHF treatment of PD and conduct KEGG pathway enrichment analysis.Import The identified differen-tial metabolites and SHF PD intersection targets were imported into the Metscape plugin,to estab-lish a"metabolite reaction enzyme gene"network,and search for key metabolites,targets,and meta-bolic pathways.RESULTS:SHF treatment could in-crease the formation of zebrafish melanin,activate tyrosinase activity,and increase melanin content.Metabolomics analysis obtained 54 differential me-tabolites,and metabolic pathway analysis was con-ducted on these metabolites,involving the biosyn-thesis of phenylalanine,tyrosine,and tryptophan,glycerol phospholipid metabolism,tyrosine metab-olism,linoleic acid metabolism,and aminoacyl tRNA biosynthesis pathways.Network pharmacolo-gy had obtained 55 cross targets of components and diseases.KEGG involved pancreatic cancer,TNF,cancer and other signal pathways.The joint analysis of metabolomics and network pharmacolo-gy identified four key targets:COMT,CYP1B1,TYR,and ALDH2;three key metabolites:L-tyrosine,ho-movanllate,L-lysine;three important metabolic pathways:tyrosine metabolism,valine/leucine/iso-leucine degradation,and lysine metabolism.CON-CLUSION:SHF has a good improvement effect on PD,and combined with metabolomics and network pharmacology,SHF may enhance its influence on the tyrosine metabolism pathway by regulating the metabolite L-tyrosine,thereby promoting the for-mation of melanin.
万方数据
维普
