Abstract
BackgroundGouty arthritis is a common metabolic disease caused by long-term purine metabolic disorder and elevated serum uric acid. Jiang-Suan-Chu-Bi recipe (JSCBR), a traditional Chinese herbal formula prescribed according to utilization frequency and cluster analysis, has been clinically validated remedy for gouty arthritis. However, its therapeutic composition and mechanism remains unclear.MethodsIn the present study, a simple, rapid, and sensitive ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS)-based chemical profiling was firstly established for comprehensively identifying the major constituents in JSCBR. A phytochemistry-based network pharmacology analysis was further performed to explore the potential therapeutic targets and pathways involved in JSCBR bioactivity. Finally, THP-1 cell model was used to verify the prediction results of network pharmacology by western blot analysis.ResultsA total of 139 compounds containing phenolic acids, flavonoids, triterpenoid saponins, alkaloids, amino acids, fatty acids, anthraquinones, terpenes, coumarins, and other miscellaneous compounds were identified, respectively. 175 disease genes, 51 potential target nodes, 80 compounds, and 11 related pathways based on network pharmacology analysis were achieved. Among these pathways and genes, NOD-like receptor signaling pathway may play an important role in the curative effect of JSCBR on gouty arthritis by regulation of NRLP3/ASC/CASP1/IL1B. The results of cellular and molecular experiments showed that JSCBR can effectively reduce the protein expression of ASC, caspase-1, IL-1β, and NRLP3 in monosodium urate-induced THP-1 cells, which indicated that JSCBR mediated inflammation in gouty arthritis by inhibiting the activation of NOD-like receptor signaling pathway.ConclusionThus, the integrated approaches adopted in the present study could contribute to simplifying the complex system and providing directions for further research of JSCBR.
Highlights
Gouty arthritis is a metabolic disease caused by the deposition of monosodium urate crystals in joints and soft tissues (Pascart et al, 2018) and closely associated with chronic hyperuricemia, which seriously affects quality of life of patients due to severe pain (Nielsen et al, 2018)
The results suggested that the antiinflammation of Jiang-Suan-Chu-Bi recipe (JSCBR) on gouty arthriris was associated with inhibition of associated speck-like protein (ASC), caspase-1, IL-1b, and NOD-like receptor protein-3 inflammasome (NLRP3) protein expression, which belongs to NOD-like receptor signaling pathway
An integrated approach based on chemical profile, network pharmacology and experimental support using molecular cell biology were carried out to reveal the therapeutic composition and mechanisms of JSCBR against gouty arthritis
Summary
Gouty arthritis is a metabolic disease caused by the deposition of monosodium urate crystals in joints and soft tissues (Pascart et al, 2018) and closely associated with chronic hyperuricemia, which seriously affects quality of life of patients due to severe pain (Nielsen et al, 2018). Western medicines including colchicine, allopurinol, benzbromarone, and febuxostat have been used as the conventional therapy method for gouty arthritis. Their short-term effect on inhibiting uric acid production, promoting uric acid excretion, or analgesic effect is optimistic, the side effects such as skin mucosal injury, kidney and liver injury, digestive tract injury, as well as some potential neurotoxicity and muscular toxicity caused by long-term use could not be ignored. As the main form of traditional Chinese medicine (TCM) that based on the compatibility theory, traditional Chinese herbal formula has been applied for the treatment of gouty arthritis for thousands of years in view of remarkable therapeutic effect and little adverse reactions (Zhou et al, 2014).
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