ABSTRACT
Wuwei Shexiang Pill (WSP) is a Tibetan traditional medicine, which has been demonstrated to exhibit potent anti-inflammatory and anti-gout effects. However, the specific pharmacological mechanism is not elucidated clearly. In the present study, liquid chromatography-mass spectrometry (LC-MS)-based metabolomics was applied to investigate the alteration of serum metabolites induced by WSP treatment in MSU-induced gouty rats. Subsequently, bioinformatics was utilized to analyze the potential metabolic pathway of the anti-gout effect of WSP. The pharmacodynamic data discovered that WSP could ameliorate ankle swelling and inflammatory cell infiltration, as well as downregulate the protein expression of IL-1ß, p-NF-κB p65, and NLRP3 in the synovial membrane and surrounding tissues of gouty ankles. LC-MS-based metabolomics revealed that there were 30 differential metabolites in the serum between sham-operated rats and gouty ones, which were mainly involved in the metabolism of fructose and mannose, primary bile acid biosynthesis, and cholesterol metabolism. However, compared to the model group, WSP treatment upregulated 11 metabolic biomarkers and downregulated 31 biomarkers in the serum. KEGG enrichment analysis found that 27 metabolic pathways contributed to the therapeutic action of WSP, including linoleic acid metabolism, phenylalanine metabolism, and pantothenate and CoA biosynthesis. The comprehensive analysis-combined network pharmacology and metabolomics further revealed that the regulatory network of WSP against gout might be attributed to 11 metabolites, 7 metabolic pathways, 39 targets, and 49 active ingredients of WSP. In conclusion, WSP could ameliorate the inflammation of the ankle in MSU-induced gouty rats, and its anti-gout mechanism might be relevant to the modulation of multiple metabolic pathways, such as linoleic acid metabolism, phenylalanine metabolism, and pantothenate and CoA biosynthesis. This study provided data support for the secondary development of Chinese traditional patent medicine.
ABSTRACT
Rapid dissemination of the plasmid-born polymyxin resistance gene mcr-1 poses a critical medical challenge. MCR-1 expression is tightly controlled and imposes a fitness cost on the bacteria. We used growth studies and metabolomics to examine growth and metabolic changes within E. coli TOP10 at 8 and 24 h in response to different levels of expression of mcr-1. Induction of mcr-1 greatly increased expression at 8 h and markedly reduced bacterial growth; membrane disruption and cell lysis were evident at this time. At 24 h, the expression of mcr-1 dramatically declined with restored growth and membrane integrity, indicating regulation of mcr-1 expression in bacteria to maintain membrane homeostasis. Intermediates of peptide and lipid biosynthesis were the most commonly affected metabolites when mcr-1 was overexpressed in E. coli. Cell wall biosynthesis was dramatically affected with the accumulation of lipids including fatty acids, glycerophospholipids and lysophosphatidylethanolamines, especially at 8 h. In contrast, levels of intermediate metabolites of peptides, amino sugars, carbohydrates and nucleotide metabolism and secondary metabolites significantly decreased. Moreover, the over-expression of mcr-1 resulted in a prolonged reduction in intermediates associated with pentose phosphate pathway and pantothenate and CoA biosynthesis. These findings indicate that over-expression of mcr-1 results in global metabolic perturbations that mainly involve disruption to the bacterial membrane, pentose phosphate pathway as well as pantothenate and CoA biosynthesis.
ABSTRACT
This study was aimed to analyze the plasma metabolicomics pathway in rats with heart blood stasis syn-drome. KEGG database was used in the signal pathway analysis. HMDB was used in the analysis of molecular metabolite annotation, enzyme or transporter associated and its related properties. The metPA network software was used in the visualization of metabolite path. The results showed that 9 metabolites involved in 15 metabolic pathways. Among them, the P-value of metabolic pathway of pantothenate and CoA biosynthesis, propanoate metabolism, biosynthesis of unsaturated fatty acids was less than 0.05. It was concluded that the metabolic pathways of pan-tothenate and CoA biosynthesis, propanoate metabolism, biosynthesis of unsaturated fatty acids were involved with the pathological process of rats with heart blood stasis syndrome.
