Revealing the pharmacological effect and mechanism of darutoside on gouty arthritis by liquid chromatography/mass spectrometry and metabolomics

Abstract

Darutoside is a diterpenoids compound with significant anti-inflammatory activity, however the pharmacological action and mechanism are still unclear. Metabolomics strategy was used to uncovering the pharmacological action and effective mechanism of darutoside against acute gouty arthritis rats. Liquid chromatography coupled with mass spectrometry technique was performed to explore the serum metabolites and potential pathways. We found that darutoside can up-regulate the level of glutamate, alanine, chenodeoxycholic acid, 1-methyladenosine, aspartic acid, citric acid, and down-regulate the level of valine, isoleucine, glutamine, alanyl-threonine, pyruvic acid, gamma-aminobutyric acid, uric acid. Metabolic pathway analysis showed that the therapeutic effect of darutoside was involved in amino acid metabolism, sugar metabolism, fatty acid metabolism, energy metabolism, purine metabolism and butanoate metabolism. It indicated that darutoside protect against acute gouty arthritis by regulating the expression of the key protein targets. It revealed that the mechanism of darutoside on acute gouty arthritis, which may be leading to the changes of serum metabolites, metabolic pathways and key protein targets to improve immune system response, inhibit oxidative stress and inflammatory response. It provides a novel method for molecular mechanisms of natural product in the disease treatment.

Phospholipase A2 regulates autophagy in gouty arthritis: proteomic and metabolomic studies

“…Clinically, AGA is most common in major joints, especially the first metatarsophalangeal, ankle, and foot joints. AGA will enter the intermittent symptomatic acute gouty arthritis (ISAGA) phase after uric acid lowering therapy (ULT) or resolve spontaneously [ 4 , 5 ]. It affects up to 1–2% of adults and is the most common form of inflammatory arthritis in men.…”

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

“…Metabolomics is a systematic approach to analyzing the small molecules metabolites in biological samples and unveiling the underlying mechanisms of altered endogenous metabolites in physiological and pathological states or stimulated by exogenous substances ( Fu et al, 2023 ). Untargeted metabolomics is used to analyze changes in biological endogenous metabolites and enrich for metabolic pathways via high-throughput assays, which is widely used in the fields of pharmacology, drug toxicology, modernization of Chinese medicine, and so on ( Li et al, 2021 ; Wang and Sun, 2022 ; Wang et al, 2023 ; Huang et al, 2023 ). Recently, a large number of works of literature have documented that metabolomics was a novel and high-performance strategy to screen the predictive biomarkers of gout flares and to unveil the molecular mechanism of anti-GA TCMs ( Huang et al, 2019 ; Lyu et al, 2019 ; Wang and Sun, 2022 ; Gu et al, 2023 ; Lei et al, 2023 ).…”

“…Untargeted metabolomics is used to analyze changes in biological endogenous metabolites and enrich for metabolic pathways via high-throughput assays, which is widely used in the fields of pharmacology, drug toxicology, modernization of Chinese medicine, and so on ( Li et al, 2021 ; Wang and Sun, 2022 ; Wang et al, 2023 ; Huang et al, 2023 ). Recently, a large number of works of literature have documented that metabolomics was a novel and high-performance strategy to screen the predictive biomarkers of gout flares and to unveil the molecular mechanism of anti-GA TCMs ( Huang et al, 2019 ; Lyu et al, 2019 ; Wang and Sun, 2022 ; Gu et al, 2023 ; Lei et al, 2023 ). Huang et al proposed that the metabolomics signatures of gout sufferings in the serum are mainly comprised of several metabolic pathways, including purine metabolism, branched-chain amino acids metabolism, and the tricarboxylic acid cycle and bile secretion and arachidonic acid metabolism ( Huang et al, 2020 ).…”