Exploring the Therapeutic Composition and Mechanism of Jiang-Suan-Chu-Bi Recipe on Gouty Arthritis Using an Integrated Approach Based on Chemical Profile, Network Pharmacology and Experimental Support Using Molecular Cell Biology

Abstract

Background: Gouty 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.Methods: In 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.Results: A 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-1b, and NRLP3 in monosodium urate-induced THP-1 cells, which Frontiers in Pharmacology | www.frontiersin.org

Identification of Interleukin-1-Beta Inhibitors in Gouty Arthritis Using an Integrated Approach Based on Network Pharmacology, Molecular Docking, and Cell Experiments

“…A fresh complete culture medium was added and cultured for 24 h after washing the cells with phosphate-buffered saline (PBS). Differentiated THP-1 cells were then stimulated with MSU (50, 100, and 200 μ g/mL) with optimal concentration and treated with TFDC at final concentrations of 25, 50, 75, 100, and 125 μ g/mL as well as colchicine (positive drug, 2 μ g/mL) simultaneously at 37°C for 24 h [ 33 ].…”

Effects and Mechanisms of Traditional Chinese Medicine and Related Active Constituents Treating Gout

“…Jiangsuan-Chubi formula (JCF) was a traditional Chinese medicine prescription obtained through clustering analysis and frequency of use, consisting of 12 Chinese herbal medicines (Table 10) and used clinically to treat gouty arthritis. JCF has been shown in studies to inhibit the secretion of the inflammatory factor IL-1β by inhibiting the expression of the NRLP3 protein, resulting in an anti-gouty arthritis effect [147]. Qingre-Lishi decoction (QLD) is made up of 12 Chinese herbal medicines (Table 10) and is used to promote blood circulation, remove blood stasis, and relieve pain.…”

How Aconiti Radix Cocta can Treat Gouty Arthritis Based on Systematic Pharmacology and UPLC-QTOF-MS/MS

“…Fresh complete culture medium was added and cultured allowed for 24 h after washing cells with phosphate-buffered saline. Then, differentiated THP-1 cells were stimulated with MSU (25,50,100,150,200,300,400 or 500 mg/ml) and treated with aurantiamide acetate (AA) at a final concentration of 0, 20, 60, 80 or 100 µM as well as colchicine (positive control, 5 µM) simultaneously for 24 h at 37 C (Xiao et al, 2019). After treatment, 10 μL of CCK-8 was added to each well, and the plates were incubated for an additional 1.5 h. Absorbance at 450 nm was measured (using 600 nm as a reference wavelength) on a SpectraMax ™ M2 reader (Molecular Devices, Silicon Valley, CA, United States).…”