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

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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.

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Most cited references 71

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Colin A. Smith, Elizabeth J. Want, Grace O'Maille … (2006)

Metabolite profiling in biomarker discovery, enzyme substrate assignment, drug activity/specificity determination, and basic metabolic research requires new data preprocessing approaches to correlate specific metabolites to their biological origin. Here we introduce an LC/MS-based data analysis approach, XCMS, which incorporates novel nonlinear retention time alignment, matched filtration, peak detection, and peak matching. Without using internal standards, the method dynamically identifies hundreds of endogenous metabolites for use as standards, calculating a nonlinear retention time correction profile for each sample. Following retention time correction, the relative metabolite ion intensities are directly compared to identify changes in specific endogenous metabolites, such as potential biomarkers. The software is demonstrated using data sets from a previously reported enzyme knockout study and a large-scale study of plasma samples. XCMS is freely available under an open-source license at http://metlin.scripps.edu/download/.

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Gout-associated uric acid crystals activate the NALP3 inflammasome.

Fabio Martinon, Virginie Pétrilli, Annick Mayor … (2006)

Development of the acute and chronic inflammatory responses known as gout and pseudogout are associated with the deposition of monosodium urate (MSU) or calcium pyrophosphate dihydrate (CPPD) crystals, respectively, in joints and periarticular tissues. Although MSU crystals were first identified as the aetiological agent of gout in the eighteenth century and more recently as a 'danger signal' released from dying cells, little is known about the molecular mechanisms underlying MSU- or CPPD-induced inflammation. Here we show that MSU and CPPD engage the caspase-1-activating NALP3 (also called cryopyrin) inflammasome, resulting in the production of active interleukin (IL)-1beta and IL-18. Macrophages from mice deficient in various components of the inflammasome such as caspase-1, ASC and NALP3 are defective in crystal-induced IL-1beta activation. Moreover, an impaired neutrophil influx is found in an in vivo model of crystal-induced peritonitis in inflammasome-deficient mice or mice deficient in the IL-1beta receptor (IL-1R). These findings provide insight into the molecular processes underlying the inflammatory conditions of gout and pseudogout, and further support a pivotal role of the inflammasome in several autoinflammatory diseases.

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MassBank: a public repository for sharing mass spectral data for life sciences.

Hisayuki Horai, Masanori Arita, Shigehiko Kanaya … (2010)

MassBank is the first public repository of mass spectra of small chemical compounds for life sciences (<3000 Da). The database contains 605 electron-ionization mass spectrometry (EI-MS), 137 fast atom bombardment MS and 9276 electrospray ionization (ESI)-MS(n) data of 2337 authentic compounds of metabolites, 11 545 EI-MS and 834 other-MS data of 10,286 volatile natural and synthetic compounds, and 3045 ESI-MS(2) data of 679 synthetic drugs contributed by 16 research groups (January 2010). ESI-MS(2) data were analyzed under nonstandardized, independent experimental conditions. MassBank is a distributed database. Each research group provides data from its own MassBank data servers distributed on the Internet. MassBank users can access either all of the MassBank data or a subset of the data by specifying one or more experimental conditions. In a spectral search to retrieve mass spectra similar to a query mass spectrum, the similarity score is calculated by a weighted cosine correlation in which weighting exponents on peak intensity and the mass-to-charge ratio are optimized to the ESI-MS(2) data. MassBank also provides a merged spectrum for each compound prepared by merging the analyzed ESI-MS(2) data on an identical compound under different collision-induced dissociation conditions. Data merging has significantly improved the precision of the identification of a chemical compound by 21-23% at a similarity score of 0.6. Thus, MassBank is useful for the identification of chemical compounds and the publication of experimental data. 2010 John Wiley & Sons, Ltd.

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Author and article information

Contributors

Jirui Lang: URI : https://loop.frontiersin.org/people/2295413/overview

Yunyun Quan: URI : https://loop.frontiersin.org/people/1495320/overview

Ruirong Tan: URI : https://loop.frontiersin.org/people/1812886/overview

Junning Zhao: URI : https://loop.frontiersin.org/people/1339562/overview

Zhujun Yin: URI : https://loop.frontiersin.org/people/1180393/overview

Journal

Journal ID (nlm-ta): Front Pharmacol

Journal ID (iso-abbrev): Front Pharmacol

Journal ID (publisher-id): Front. Pharmacol.

Title: Frontiers in Pharmacology

Publisher: Frontiers Media S.A.

ISSN (Electronic): 1663-9812

Publication date (Electronic): 11 August 2023

Publication date Collection: 2023

Volume: 14

Electronic Location Identifier: 1213602

Affiliations

[1] ¹ Biological Assay Key Laboratory of State Administration of Traditional Chinese Medicine for Traditional Chinese Medicine Quality , Translational Chinese Medicine Key Laboratory of Sichuan Province , Sichuan Engineering Technology Research Center of Genuine Regional Drug , Engineering Research Center for Formation Principle and Quality Evaluation of Genuine Medicinal Materials in Sichuan Province , Sichuan Academy of Chinese Medicine Sciences , Sichuan Institute for Translational Chinese Medicine , Chengdu, China

[2] ² Hunan Provincial Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations , The “Double-First Class” Application Characteristic Discipline of Hunan Province (Pharmaceutical Science) , Changsha Medical University , Changsha, China

[3] ³ Sichuan Fengchun Pharmaceutical Co., Ltd. , Deyang, China

Author notes

Edited by: Xiaofeng Zhu, Jinan University, China

Reviewed by: Gui-Sheng Zhou, Nanjing University of Chinese Medicine, China

Ying Luo, East China Normal University, China

*Correspondence: Junning Zhao, zarmy@ 123456189.cn ; Zhujun Yin, 506591629@ 123456qq.com

Article

Publisher ID: 1213602

DOI: 10.3389/fphar.2023.1213602

PMC ID: 10450745

PubMed ID: 37637422

SO-VID: 7ccbfc47-e71b-44d7-abfc-b68e9aad7b0a

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This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

History

Date received : 28 April 2023

Date accepted : 26 July 2023

Funding

This work is supported by the Science and Technology Department of Sichuan Province, China (2023NSFSC0669, 2021JDKY0037), the Sichuan Provincial Administration of Traditional Chinese Medicine, China (ZDXK 2020-1), and the Sichuan Fengchun Pharmaceutical Co., Ltd. (D-2019-6).

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section-at-acceptance Experimental Pharmacology and Drug Discovery

ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine

Keywords: wuwei shexiang pill (wsp),gout,serum metabolomics,linoleic acid metabolism,phenylalanine metabolism,pantothenate and coa biosynthesis

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ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine

Keywords: wuwei shexiang pill (wsp), gout, serum metabolomics, linoleic acid metabolism, phenylalanine metabolism, pantothenate and coa biosynthesis

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

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Herbal Medicines Journal (Herb Med J)

Most cited references 71

XCMS: processing mass spectrometry data for metabolite profiling using nonlinear peak alignment, matching, and identification.

Gout-associated uric acid crystals activate the NALP3 inflammasome.

MassBank: a public repository for sharing mass spectral data for life sciences.

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