Abstract

Background The incidence of gout has been rapidly increasing in recent years with the changing of diet. At present, modern medications used in the clinical treatment of gout showed several side effects, such as gastrointestinal damage and the increased risk of cardiovascular disease. The traditional Chinese prescription Simiao Powder (SMP) has a long history in the treatment of acute gouty arthritis (AGA) and has a good curative effect. However, the mechanism and target of its therapeutic effects are still not completely understood. Methods Potential active compounds (PACs) and targets of SMP were found in the TCMSP database, and the disease target genes related to AGA were obtained by searching CTD, DisGeNET, DrugBank, GeneCards, TTD, OMIM, and PharmGKB disease databases with “acute gouty arthritis” and “Arthritis, Gouty” as keywords, respectively. The network of “Traditional Chinese medicine (TCM)-PACs-potential targets of acute gouty arthritis” was constructed with the Cytoscape 3.7.2 software, and the target genes of acute gouty arthritis were intersected with genes regulated by active compounds of SMP. The resultant common gene targets were input into Cytoscape 3.7.2 software, and the BisoGenet plug-in was used to construct a PPI network. The GO functional enrichment analysis and KEGG pathway enrichment analysis of the intersecting target proteins were performed using R software and corresponding program packages. The molecular docking verification was carried out between the potentially active compounds of SMP and the core target at the same time. Results 40 active components and 203 targets were identified, of which 95 targets were common targets for the drugs and diseases. GO function enrichment analysis revealed that SMP regulated several biological processes, such as response to lipopolysaccharide and oxidative stress, RNA polymerase II transcription regulator complex, protein kinase complex, and other cellular and molecular processes, including DNA-binding transcription factor binding. Results of KEGG pathway analysis showed that SMP was associated with AGA-related pathways such as interleukin-17 (IL-17), tumor necrosis factor (TNF), p53, and hypoxia-inducible factor 1 (HIF-1) signaling pathways. The results of molecular docking showed that active compounds in SMP exhibited strong binding to five core protein receptors (TP53, FN1, ESR1, CDK2, and HSPA5). Conclusions Active components of SMP, such as quercetin, kaempferol, wogonin, baicalein, beta-sitosterol, and rutaecarpine, showed therapeutic effects on AGA. These compounds were strongly associated with core target proteins (such as TP53, FN1, ESR1, CDK2, and HSPA5). This study reveals that IL-17, TNF, p53, and HIF-1 signaling pathways mediate the therapeutic effects of SMP on AGA. These findings expand our understanding of the mechanism of SMP in the treatment of AGA.

Highlights

  • Gouty arthritis (GA) is characterized by acute onset of single joint redness, swelling, heat, and pain at night or in the morning. e pain progressively worsens, and in severe cases, patients often suffer from cutting pain, which often reaches a peak within 24 hours [1]. e number of gout patients has increased drastically due to dietary changes and high intake of high-purine foods and beer [2]

  • We screened the active compounds in Simiao Powder (SMP) following the standards of oral bioavailability (OB) ≥30% and drug-likeness (DL) ≥0.18. en, a search was undertaken for corresponding targets of active compounds on the TCMSP platform. e identified drug targets were input into the UniProt database

  • 403 compounds of SMP were obtained from the TCMSP database, including 49 from Rhizoma Atractylodis (Cang Zhu), 140 from Cortex Phellodendri (Huang Bo), 176 from Radix Vladimiriae (Niu Xi), and 38 from Semen Coicis (Yi Yi Ren)

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Summary

Introduction

Gouty arthritis (GA) is characterized by acute onset of single joint redness, swelling, heat, and pain at night or in the morning. e pain progressively worsens, and in severe cases, patients often suffer from cutting pain, which often reaches a peak within 24 hours [1]. e number of gout patients has increased drastically due to dietary changes and high intake of high-purine foods and beer [2]. Gouty arthritis (GA) is characterized by acute onset of single joint redness, swelling, heat, and pain at night or in the morning. In the United States, the prevalence of gout was about 3.9% in 2016, with an estimated 9.2 million gout patients [4]. Acute gouty arthritis (AGA) is the first symptom of gout. Recurrent acute arthritis can destroy joints and damage internal organs [5]. Gout treatment guidelines issued in 2012 by the American College of Rheumatology (ACR) recommend nonsteroidal anti-inflammatory drugs (NSAIDs) or oral colchicine for acute attacks of gout [6]. Colchicine is an anti-inflammatory drug commonly used in the treatment of acute gout. When taken in large doses, it causes gastrointestinal tract discomfort, liver and kidney damage, or heart disease. It may lead to poisoning in elderly patients [8]. erefore, safer and more effective drugs for the treatment of AGA are urgently needed

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