Effect and mechanism of Huanglianjiedu decoction on high fat-induced atherosclerosisrats and metabolomics study by ultra-performance liquid chromatography-mass spectrometry / 中国药理学与毒理学杂志

ABSTRACT

OBJECTIVE To explore the biomarkers and molecular mechanism of Huanglianjiedu decoction (HJD) on high fat diet-induced experimental atherosclerosis in rats. METHODS SD male rats were randomly dividedinto five groups(n=8)normal control group,model group,and three dosage groups (1.5, 3 and 6 g crude drug per kilogram of body weight). Atherosclerosis was induced by the combination of regular intraperitoneal injection of vitamin D3and high fat diet for 8 weeks. HJD was administered by oral gavage from the third week once per day and until the end of the study.After the final administration, the blood samples were collected for biochemical analyses [total cholesterol (TC), triglycerides (TG), highdensity lipoprotein (HDL-C), low-density cholesterol (LDL-C)] and blood gas analyses(PaO2, PaCO2, pH, ctHb, etc); the abdominal aorta sections were stained with hematoxylin and eosin for histopathology; the liver homogenate were determined for MDA, SOD, OX-LDL, MCP-1 and VCAM-1.The plasma samples were detected using ultraper formance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS).The data of endogenous compounds were preliminarily preprocessed by software Progenesis QI and then analyzed by multivari-ate statistical analysis software EZinfo 2.0 to screen the distinguished biomarkers and the metabolic pathways were analyzed through website http//www.metaboanalyst.ca/. RESULTS Compared with the normal control group,the content of TC,TG,LDL-C,PaCO2,MDA,Ox-LDL,MCP-1 and VCAM-1were significantly increased and HDL-C, PaO2, ctHb and SOD decreased in the atherosclerosis rats. HJD could significantly attenuated the high fat-induced atherosclerosis pathological injury and the above-mentioned indexes (P<0.05). The five groups could be clearly distinguished using the metabolomics method.The administration groups profile exhibited an apparent returning trend from that of the model group and that of the normal control group.Twenty-one endogenous metabolites has been significantly changed in atherosclerosis rats.HJD could remarkably up-regulate 5-L-glutamyl-taurine,L-beta-aspartyl-L-glutamic acid, histidinyl-hydroxyproline, tryptophyl-alanine, 4′-O-methyl-(-)-epicatechin, and down-regulate protoporphyrin IX,azelaic acid,lacto-N-triaose,cinnamoylglycine and 9′-carboxy-alpha-tocotri-enol. CONCLUSION The beneficial effect of HJD in high fat-induced atherosclerosis rats may be due to anti-oxidant and anti-inflammatory. And it is suggested that HJD may affect the model rats through tryptophan metabolism, taurine and hypotaurine metabolism, histidine metabolism, lysine degradation and porphyrin and chlorophyll metabolism pathway.