ABSTRACT
To identify biomarkers for spleen Qi deficiency by analyzing small molecule metabolites in urine, in order to expound the relationship between biomarkers and metabolic pathways. The spleen Qi deficiency model was established through dietary restriction and overstrain. All of the rats received D-xylose absorption experiment and blood routine test. Urine samples were collected in the next day. The urine samples were analyzed using UPLC-Q-TOF-MS to obtain the dataset of urine metabolic group. Principal component analysis (PCA), orthogonal partialleast squares-discriminant analysis (OPLS-DA) and other multivariate statistical methods were employed to evaluate the quality of the dataset and screen out potential biomarkers of spleen Qi deficiency. The results of D-xylose absorption and blood routine demonstrated that the spleen Qi deficiency model was successfully established. In positive ion mode and negative ion mode, PCA and OPLS-DA score plots could clearly distinguish model group and blank group. According to S-plot of OPLS-DA, VIP value, t-test and area under receiver operating characteristic curve (ROC), 24 biomarkers, including phenylalanine, succinic acid, aconitic acid, isocitrate acid, betaine, kynurenine, indole, creatine, creatinine, orotic acid, xanthine, and xanthurenic acid, were identified as associated with the spleen Qi deficiency, mainly involving energy metabolism, amino acid metabolism, tryptophan metabolism, purine metabolism and pyrimidine metabolism. Urine metabolomics method combined with online software package for data processing and analysis metabolic pathway can provide new methods and ideas for studies for spleen Qi deficiency and other traditional Chinese medicine symptoms.
ABSTRACT
<p><b>OBJECTIVE</b>To evaluate the inhibitory effect of genistin combined with anastrozole on the growth and apoptosis of breast tumor tissue, and to study their anti-cancer mechanism by using the model of 7,12-dimethylbenz [alpha] anthracene (DMBA)-induced mammary tumors following ovariectomy in Sprague-Dawley (SD) rats.</p><p><b>METHODS</b>The DMBA induced postmenopausal SD rats were randomly divided into the control group, the genistein group, the anastrozole group, and the genistein combined with anastrozole group. The growth of tumors was observed in each group. The proliferation index and apoptosis index of tumor cells were determined. Moreover, estradiol (E2) and 17beta-HSD1 mRNA levels were determined by ELISA and RT-PCR respectively.</p><p><b>RESULTS</b>The tumor growth was inhibited in the genistein group and the anastrozole group. The inhibitory ratio was significantly higher in the genistein combined with anastrozole group (P < 0.05). Compared with the control group, levels of E2 and 17beta-HSD1 mRNA decreased more significantly in the genistein combined with anastrozole group (P < 0.05).</p><p><b>CONCLUSIONS</b>Genistein could suppress the growth of mammary tumors in postmenopausal rats. It showed synergistic effect when combined with anastrozole, which resulted in reduced levels of E2 and 17beta-HSD1 mRNA. It had inhibitory effect on the growth of breast tumors.</p>