LC-MS-based metabolomics reveals the mechanism of anti-gouty arthritis effect of Wuwei Shexiang pill

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-1β, 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.

LC-MS-Based Metabolomics Reveals the Mechanism of Protection of Berberine against Indomethacin-Induced Gastric Injury in Rats

“…In untargeted metabolic projects, two types of chromatographic columns are typically used for detecting different substances. The BEH amide column is ideal for polar metabolites, while the T3 column suits polar metabolites and some strongly polar lipid metabolites [ 19 ]. The T3 column has a broader range of applications, so it was chosen for this project.…”

“…By analyzing the correlation structure of the data, it can reveal the internal structure of multiple variables through a few principal components. PCA is capable of visually reflecting the overall distribution characteristics of all samples and trends [ 19 ]. OPLS-DA is based on partial least squares discriminant analysis (PLS-DA), which improves the interpretability and accuracy of multivariate discriminant analysis.…”

“…Accurate mass-to-charge ratios were based on differential metabolites, within a permissible range of matched mass deviations of 30 ppm. To validate the data, we compared the mass spectrometry fragment ions and isotopes with various online metabolomics databases, including HMDB (http://www.hmdb.ca/, accessed on 1 December 2023), METLIN (http://metlin.scripps.edu/, accessed on 1 December 2023) [43], massbank, and LipidMaps [19]. This was accomplished by performing data validation, which involved a detailed examination of the aforementioned databases to ensure consistency between the metabolites under investigation and their corresponding entries in the databases.…”

“…Untargeted metabolomics is a scientific approach that examines alterations in biological endogenous metabolites and identifies metabolic pathways using high-throughput assays. This method is commonly used to comprehend the construction and operation mechanisms of metabolic networks in living organisms like pharmacology, drug toxicology, and the modernization of Chinese medicine [ 19 , 20 ].…”

Characterization of active peptides derived from three leeches and comparison of their anti-thrombotic mechanisms using the tail vein thrombosis model in mice and metabonomics

“…The dynamic changes in the metabolite profile will help identify perturbations at the genomic and protein levels that cause disease and are closely associated with phenotypic changes. Furthermore, comprehensive analyses of metabolite biomarkers, metabolic pathway profiles, and drug-target interactions can be used to elucidate the pathogenetic mechanisms underlying specific human diseases and the mechanism of action of drugs and other treatments ( Lang et al, 2023 ; McMillen et al, 2023 ). Metabolic profiling has also been used to discover novel biomarkers and assess the holistic effects of many therapeutic components in various TCM preparations.…”