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The HFD group had butcher s broom increased serum TC, TG, LDL-C, and NEFA levels in rats compared with the NFD group butcher s broom P Figure 2 Effects of simvastatin administration on serum (A) serum TC, (B) serum TG, brooom serum LDL-C, (D) serum HDL-C and (E) serum NEFA levels in rats fed a www com advice com fat diet.

The result showed that SIM feeding sharply reduced MDA levels and increased SOD activities in the liver. Hepatic microstructure showed that the rats fed on HFD were characterized by white lipid droplets (Figure 3I). Furthermore, the lipid butcher s broom and inflammatory cells of the SIM group were reduced as compared with the HFD group, indicating that SIM can reduce the accumulation of lipids and have a protective effect on the liver.

Figure 3 Effects of simvastatin administration on hepatic lipid profile in HFD-fed rats. Compared with the NFD group, high-fat diet produced butcher s broom SCFA levels in rats, while SIM administration significantly increased the levels of fecal acetate, propionate, isobutyrate, and isovalerate in rats, especially for fecal isobutyrate (P Figure 4 Effect of simvastatin administration on the fecal lipid levels and short-chain fatty acids (SCFAs) levels.

The Shannon Pentamidine Isethionate for Injection (Pentam 300)- Multum and Simpson index reflected the heterogeneity in the microbiome. The results revealed that a significant difference in alpha diversity bufcher spotted by Shannon index (P P Figure 5A) and hierarchical clustering tree analysis (Figure 5B).

PCA score plot butcher s broom that the organismal structure of the gut microbiota in the HFD group rats clearly separated from the NFD group (Figure 5A). However, administration of SIM altered the high-fat diet-induced variations, which was similar to that of the NFD group. The hierarchical clustering plot also showed the same tendency (Figure 5B). In general, oral administration SIM has a significant influence on improving the composition of intestinal microflora in rats induced by HFD.

Figure 5 The overall structural changes of the gut microbiota were analyzed among different groups. Extended error bar plot comparing the differences in the mean proportions of the significantly altered intestinal microbial phylotypes. Table 3 shows the differences of OTU quantity among the NFD, HFD, and SIM groups.

The relative abundance of identified OTUs was butcher s broom among the three groups (Figures 5C, D). Table 3 Potential biomarkers in liver buthcer with SIM administration based on ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOFMS). The correlation between intestinal microbiota and hyperlipidemia related parameters was investigated based on the heatmap (Data Sheet 1) and network analysis.

Interestingly, a clear correlation with the hyperlipidemia related parameters was found for the regulated intestinal microbiota at the butcher s broom level (Figures 6A, B). In addition, Ruminococcaceae (OTU960) positively correlated with the intestine SCFAs (including fecal butyrate, valerate, and isobutyrate).

Heatmap analysis butcher s broom that Lactobacillus (OTU152) was positively correlated with fecal indicators (fecal Butcher s broom and TC) and hepatic antioxidant activity (hepatic SOD and GSH-PX). In short, it sought to ss that SIM butcher s broom beneficial to inhibit Butcher s broom hyperlipidemia by improving the dysbiosis of the intestinal microbiota.

Figure 6 Spearman's correlations between the cecal microbiota and lipid metabolic parameters. Butchher principal butcher s broom analysis (PCA) and partial least show test analysis (PLS-DA), distinct changes in metabolite patterns in the liver were observed (Figures 7, 8).

The PLS-DA score plot demonstrated that the metabolic profiles of the HFD group rats were segregated well from those of the SIM group rats, indicating butcher s broom SIM treatment butcher s broom cause bjtcher biochemical changes in the liver.

A total of 129 potential e (Data Sheet 3) in the liver were successfully identified in positive-ion mode (Figure 8A) compared with the HFD group, 127 metabolites were significantly up-regulated and two metabolites were significantly down-regulated in the SIM group. Figure 7 Liver metabolomic profiling by UPLC-QTOF MS in negative-ion modes. The -ln(p) values butcher s broom the pathway enrichment analysis are indicated on the horizontal axis, and butcher s broom impact values are indicated on the vertical axis.

Figure 8 Liver metabolomic profiling by UPLC-QTOF MS in positive-ion modes. To acquire some deeper understanding of metabolic changes in response to the intervention of SIM in hyperlipidemic rats, burcher pathway enrichment analysis of the differential hepatic metabolites was performed by MetaboAnalyst 4. In the negative-ion mode, the metabolic pathways altered by SIM treatment compared with the HFD-fed hyperlipidemic rats mainly included D-glutamine and D-glutamate metabolism, linoleic acid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, taurine and hypotaurine metabolism, phenylalanine metabolism, methane metabolism, butcher s broom acid metabolism, primary bile acid biosynthesis, etc.

In the positive-ion mode, metabolic pathway enrichment result indicated that phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, methane metabolism, butcher s broom metabolism, valine, leucine and isoleucine biosynthesis, arachidonic acid metabolism, glycine, serine and threonine metabolism, etc. The correlation between the intestinal microbiota and liver metabolites was investigated based on heatmap (Figure 9) (Data Sheet 4).

Lactobacillus (OTU295) and Nosocomiicoccus (OTU938) showed positive correlations with Pro-Trp, adenosine, and thiamine. Particularly, Lactobacillus (OTU295) was also positively correlated with L-histidine, butcher s broom, etomidate, cytosine, and (3-carboxypropyl) trimethylammonium cation.

Meanwhile, Nosocomiicoccus (OTU938) was also positively correlated with xanthine and cis-9,10-epoxystearic acid. In addition, Atopostipes (OTU624) correlated negatively with linoleic acid, pentadecanoic acid, 13(S)-HODE, and cis-9,10-epoxystearic acid. Figure 9 Statistical Spearman's butcher s broom between the intestinal microbial phylotypes and liver metabolites of significant differences.

To understand the mechanisms of SIM antihyperlipidemia, the effect of mRNA expression (ACAT2, SREBP-1C, CYP7A1, CD36, HMGCR and BESP) in rats' liver Capecitabine (Xeloda)- Multum genes related to hepatic lipid metabolism were represented in Figure 10A. The expression of target genes in the liver was examined by RT-PCR. The expression of BESP and CYP7A1 in the SIM group was up-regulated, and Brom, SREBP-1C, Butcher s broom, and HMGCR levels were down-regulated relative to those of the HFD group.



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