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

Jirui Lang; Li Li; Yunyun Quan; Ruirong Tan; Jinbiao Zhao; Min Li; Jin Zeng; Shilong Chen; Ting Wang; Yong Li; Junning Zhao; Zhujun Yin

doi:10.3389/fphar.2023.1213602

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

Front Pharmacol. 2023 Aug 11:14:1213602. doi: 10.3389/fphar.2023.1213602. eCollection 2023.

Authors

Jirui Lang¹, Li Li¹, Yunyun Quan¹, Ruirong Tan¹, Jinbiao Zhao², Min Li¹, Jin Zeng¹, Shilong Chen¹, Ting Wang¹, Yong Li³, Junning Zhao¹, Zhujun Yin^{1

2}

Affiliations

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 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 Sichuan Fengchun Pharmaceutical Co., Ltd., Deyang, China.

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.

Keywords: Wuwei Shexiang pill (WSP); gout; linoleic acid metabolism; pantothenate and CoA biosynthesis; phenylalanine metabolism; serum metabolomics.

Grants and 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).