Preliminary Evaluation Of Metabolomic On The Intervention Of Polyrhachis Vicina Roger In Perimenopausal Syndrome And The Mechanism Of MFC Tumor-bearing Mice

Objective:(1)The purpose of this study was to preliminarily explore the protective effect of ethyl alcohol extract of Polyrhachis vicina Roger(EAPR)on perimenopausal syndrome rats induced by bilateral ovariectomized(OVX).Based on ~1H NMR metabolomics and multivariate statistical analysis,the metabolic changes of perimenopausal syndrome induced by OVX were studied,and the comparative analysis was used to clarify the changes of differential metabolites caused by EAPR for OVX,so as to provide scientific basis for its application in improving the perimenopausal syndrome;(2)The changes of liver metabolic profile of MFC tumor-bearing mice were studied from the perspective of metabolomics.By analyzing differential metabolites and related metabolic pathways,understand the pathological mechanism of MFC tumor-bearing mice,and provide a theoretical basis for the study of the pathological mechanism of gastric cancer and anticancer drugs.Methods:(1)Female rats were randomly divided into 6 groups(n=8):normal control group(Normal),model group(OVX),OVX+Low dose EAPR(L-EAPR,100mg/kg),OVX+Middle dose EAPR(M-EAPR,200mg/kg),OVX+High dose EAPR(H-EAPR,400mg/kg),and OVX+Positive control estradiol valerate tablets group(EVT,0.1mg/kg).~1H NMR spectrum of each group was collected,followed by Fourier transform,baseline and phase adjustment,calibration and normalization,and the data were analyzed by multivariate data analyze such as PCA,PLS-DA and OPLS-DA.In combination with HMDB database and relevant literature,the potential hepatic metabolic differences of perimenopausal syndrome rats induced by ovariectomy were screened.Comparative analysis of differential metabolite changes and the regulation of metabolic pathways caused by the EAPR intervened in OVX,to explore the preliminary metabolomic mechanism of the EAPR on the liver of OVX rats;(2)Mice were randomly divided into normal control group,the MFC tumor-bearing mice model group.The differential metabolites and metabolic pathways in the liver tissue extracts of normal control mice and MFC tumor-bearing mice were analyzed by ~1H NMR metabolomics,and combined with multivariate statistics,such as PCA,PLS-DA and OPLS-DA.Results:(1)Studies based on ~1H NMR metabolomics,compared with the normal control group,lactate levels in liver tissue of ovariectomized rats were significantly increased,glutathione,glutamine,glutamate,ascorbate,adenosine,methionine,myo-inositol and arginine levels are significantly reduced,whereas EAPR can reverse the metabolic changes except inositol,which are involved in metabolic pathways such as energy metabolism(lactate),methionine metabolism(adenosine,methionine),oxidative stress(glutathione,glutamine,glutamate,ascorbate)and arginine metabolism(arginine);(2)Based on ~1H NMR metabolomics studies,eight potential differential metabolites were identified in the liver extract.Compared with the normal control group,the levels of arginine,maltose and taurine in the liver tissues of MFC tumor-bearing mice increased,and the levels of choline,glucose,inosine,hydroxyproline and NAD~+decreased.Conclusions:(1)OVX can cause multiple metabolites and metabolic pathway disorder in the rat liver.EAPR has certain protective effects on perimenopausal syndrome induced by OVX.Its liver metabolomics mechanism may be related to the regulation of energy metabolism,methionine metabolism,oxidative stress and arginine metabolism;(2)The metabolic pathways such as glycolysis,arginine metabolism and choline metabolism etc in the liver of MFC tumor-bearing mice were disordered.