Pharmacological Basis for Use of a Novel Compound in Hyperuricemia: Anti-Hyperuricemic and Anti-Inflammatory Effects

Zhao, Lei; Sun, Run‐Cang; Liu, Shifang; Chen, Xi; Lin, Caiyu; Huang, Jian; Wang, Jinhui; Li, Guang

doi:10.3389/fphar.2021.772504

Cited by 11 publications

(8 citation statements)

References 54 publications

(58 reference statements)

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“…Interestingly, some of these core targets were proinflammatory factors, such as TNF, IL6, and IL1B. Evidence has demonstrated that inflammation is significantly implicated in the pathogenesis of HUA [51][52][53]. Specifically, Nod-like receptor protein 3 (NLRP3) inflammasome is frequently activated during HUA, leading to the secretion of IL1B and other proinflammatory cytokines [52].…”

Section: Discussionmentioning

confidence: 99%

“…Evidence has demonstrated that inflammation is significantly implicated in the pathogenesis of HUA [51][52][53]. Specifically, Nod-like receptor protein 3 (NLRP3) inflammasome is frequently activated during HUA, leading to the secretion of IL1B and other proinflammatory cytokines [52]. Furthermore, an in vivo study has indicated that TLR4 inactivation-induced downregulation of TNF, IL6, and IL1B can mitigate the pathological injury of HUA [54].…”

Section: Discussionmentioning

confidence: 99%

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[Retracted] A Network Pharmacology Method Combined with Molecular Docking Verification to Explore the Therapeutic Mechanisms Underlying Simiao Pill Herbal Medicine against Hyperuricemia

Yin

et al. 2023

BioMed Research International

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Objective. Hyperuricemia (HUA) is a common metabolic disease caused by disordered purine metabolism. We aim to reveal the mechanisms underlying the anti-HUA function of Simiao pill and provide therapeutic targets. Methods. Simiao pill-related targets were obtained using Herbal Ingredients’ Targets (HIT), Traditional Chinese Medicine Systems Pharmacology (TCMSP), and Traditional Chinese Medicine Integrated Database (TCMID). HUA-associated targets were retrieved from GeneCards, DisGeNET, and Therapeutic Targets Database (TTD). Protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, ggraph and igraph R packages. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using ClusterProfiler. The top 10 core targets were identified through cytoHubba. Molecular docking was conducted using PyMOL and AutoDock high-performance liquid chromatograph (HPLC) analysis was performed to identify effective compounds of Simiao pill. Results. Simiao pill-HUA target network contained 80 targets. The key targets were mainly involved in inflammatory responses. Insulin (INS), tumor necrosis factor (TNF), interleukin-6 (IL6), interleukin 1 beta (IL1B), vascular endothelial growth factor A (VEGFA), leptin (LEP), signal transducer and activator of transcription 3 (STAT3), C-C motif chemokine ligand 2 (CCL2), interleukin-10 (IL10), and toll like receptor 4 (TLR4) were the top 10 targets in the PPI network. GO analysis demonstrated the main implication of the targets in molecular responses, production, and metabolism. KEGG analysis revealed that Simiao pill might mitigate HUA through advanced glycation end-product- (AGE-) receptor for AGE- (RAGE-) and hypoxia-inducible factor-1- (HIF-1-) associated pathways. IL1B, IL6, IL10, TLR4, and TNF were finally determined as the promising targets of Simiao pill treating HUA. Through molecular docking and HPLC analysis, luteolin, quercetin, rutaecarpine, baicalin, and atractylenolide I were the main active compounds. Conclusions. Simiao pill can mitigate HUA by restraining inflammation, mediating AGE-RAGE- and HIF-1-related pathways, and targeting IL1B, IL6, IL10, TLR4, and TNF.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

[Retracted] A Network Pharmacology Method Combined with Molecular Docking Verification to Explore the Therapeutic Mechanisms Underlying Simiao Pill Herbal Medicine against Hyperuricemia

Yin

et al. 2023

BioMed Research International

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“…HE staining is the most basic pathology staining technique. It is used to observe pathological changes of tissues and cells [ 29 ]. Results from our histopathological analysis demonstrated that the cells were swollen or even necrotic and disappeared, with no apparent intercellular demarcation in the cold group, and further proved cold stress-induced mouse liver pathological damages.…”

Section: Discussionmentioning

confidence: 99%

Cold Stress Induced Liver Injury of Mice through Activated NLRP3/Caspase-1/GSDMD Pyroptosis Signaling Pathway

et al. 2022

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The body needs to generate heat to ensure basic life activities when exposed to cold temperatures. The liver, as the largest glycogen storage organ in the body and main heat-producing organ at rest, may play a role in chronic cold exposure. Recent studies suggested that pyroptosis plays a crucial role in liver diseases. However, the role of pyroptosis in cold stress-induced liver injury is not clear. Hence, in this study, we attempted to investigate the effects of chronic cold exposure on liver function, apoptosis, oxidative stress and inflammation in mice by establishing a mouse model of chronic cold exposure, and to investigate whether pyroptosis pathways are involved in the process of chronic cold exposure. In vivo, our results show that inflammatory cell infiltration and other pathological changes in liver cells and the activity of liver enzyme evidently increased in the serum and liver of cold-exposed mice, suggesting cold stress may result in liver injury. Remarkably, increased expression of heat shock protein 70 (HSP70) and HSP90 proteins proved the cold stress model is successfully constructed. Then, elevated levels of apoptosis, inflammation, oxidative stress and pyroptosis related proteins and mRNAs, such as cysteinyl aspartate specific proteinase-3 (Caspase-3), inducible nitric oxide synthase (iNOS), nuclear factor erythroid2-related factor 2 (Nrf2) and gasdermins D (GSDMD), confirmed that cold exposure activated apoptosis, oxidative stress and pyroptosis, and released inflammation cytokines. Meanwhile, in vitro, we got similar results as in vivo. Further, adding an NLR family pyrin domain containing 3 (NLRP3) inhibitors found that suppression expression of NLRP3 results in the essential proteins of pyroptosis and antioxidant evidently reduced, and adding GSDMD inhibitor found that suppression expression of GSDMD accompanies with the level of Nrf2 and heme oxygenase-1 (HO-1) obviously reduced. In summary, these findings provide a new understanding of the underlying mechanisms of the cold stress response, which can inform the development of new strategies to combat the effects of hypothermia.

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“…A P-value of less than 0.05 was considered significant. This data set has been previously published as the GEO dataset series GSE186871 ( https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE186871 ) 31 .…”

Section: Mouse Model and Kidney Sample Rna Sequencingmentioning

confidence: 99%

Exploring the mechanism underlying hyperuricemia using comprehensive research on multi-omics

Liu¹,

Xie²,

Dai³

et al. 2023

Sci Rep

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Hyperuricemia involves multiple complex metabolisms, but no study has conducted a comprehensive analysis using human blood and urine metabolomics for hyperuricemia. Serum and urine samples from 10 patients with hyperuricemia and 5 controls were collected and analyzed by the UHPLC-MS/MS. Differential metabolites were identified and used in the enrichment analysis where we collected hyperuricemia target genes. Hyperuricemia kidney differential expressed genes (DEGs) were identified using RNA-sequencing data from the hyperuricemia mouse model induced by the potassium oxonate. A Mendelian randomization analysis of the association between caffeine-containing drinks and gout risk was conducted. An intersection analysis between hyperuricemia target genes and hyperuricemia kidney DEGs was conducted and the resulting genes were used for network analysis using the STRING. 227 differential metabolites were identified as differential metabolites and were enriched in 7 KEGG pathways, among which “Caffeine metabolism” was the top. The Mendelian randomization analysis revealed a significant association between tea or coffee intake and gout risk. There were 2173 genes that were identified as hyperuricemia kidney DEGs from mouse data. The intersection analysis identified 51 genes for the hyperuricemia regulation network. A hyperuricemia regulation protein network in the kidney was constructed. This study suggested a potential association between caffeine and hyperuricemia and constructed a hyperuricemia regulation network for future reference.

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Pharmacological Basis for Use of a Novel Compound in Hyperuricemia: Anti-Hyperuricemic and Anti-Inflammatory Effects

Cited by 11 publications

References 54 publications

[Retracted] A Network Pharmacology Method Combined with Molecular Docking Verification to Explore the Therapeutic Mechanisms Underlying Simiao Pill Herbal Medicine against Hyperuricemia

[Retracted] A Network Pharmacology Method Combined with Molecular Docking Verification to Explore the Therapeutic Mechanisms Underlying Simiao Pill Herbal Medicine against Hyperuricemia

Cold Stress Induced Liver Injury of Mice through Activated NLRP3/Caspase-1/GSDMD Pyroptosis Signaling Pathway

Exploring the mechanism underlying hyperuricemia using comprehensive research on multi-omics

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