Gouty nephropathy (GN) is a metabolic disease with persistently elevated blood uric acid levels. The main manifestations of GN are crystalline kidney stones, chronic interstitial nephritis, and renal fibrosis. Understanding the mechanism of the occurrence and development of GN is crucial to the development of new drugs for prevention and treatment of GN. Currently, most studies exploring the pathogenesis of GN are primarily based on animal and cell models. Numerous studies have shown that inflammation, oxidative stress, and programmed cell death mediated by uric acid and sodium urate are involved in the pathogenesis of GN. In this article, we first review the mechanisms underlying the abnormal intrinsic immune activation and programmed cell death in GN and then describe the characteristics and methods used to develop animal and cell models of GN caused by elevated uric acid and deposited sodium urate crystals. Finally, we propose potential animal models for GN caused by abnormally high uric acid levels, thereby provide a reference for further investigating the methods and mechanisms of GN and developing better prevention and treatment strategies.

Xuefu Zhuyu Capsule (XFZYC) plays a pivotal role in treating coronary heart disease (CHD) because of its potent clinical effects and fewer side effects. However, the possible pharmacological effect on CHD is limited. Thus, this research systematically analyzes XFZYC and CHD through network pharmacology technology. We identified 139 active compounds and 127 overlapped target genes in 11 herbs of XFZYC by using network pharmacology, and these 127 genes regulated the major signaling pathways related to CHD. The analysis of protein–protein interaction networks demonstrated that 30 important gene targets, such as interleukin-6, signal transducer and activator of transcription 3, protein kinase B1, mitogen activated protein kinases 3, cellular tumor antigen p53, vascular endothelial growth factor A, transcription factor p65, and proto-oncogene c-Fos, participated in the regulation of 79 major signaling pathways related to CHD. On this basis, we found that protein kinase B1, cellular tumor antigen p53, and transcription factor p65, which played a role in multiple regulatory pathways of the network, were also regulated by more than 3 compounds and expressed in at least 4 herbs. Molecular docking showed that XFZYC had a good binding potential with the overlapped protein targets. Gene Ontology enrichment analysis revealed that the active targets involved a various of biological process, cellular component, and molecular function, which included the key ones such as positive regulation of transcription from RNA polymerase II promoter, plasma membrane, and protein binding. T cell receptor signaling pathway, programmed death-ligand 1 expression and programmed death cell receptor-1 checkpoint pathway in cancer, FOXO signaling pathway, Ras signaling pathway, interleukin-17 signaling pathway, and VEGF signaling pathway, which were selected from Kyoto Encyclopedia of Genes and Genomes, were closely related to XFZYC in the treatment of CHD. XFZYC has a potential pharmacological effect on CHD, which provides the value for further study of XFZYC’s therapeutic effect on CHD.

Ferroptosis, an emerging form of iron-dependent programmed cell death, has recently gained substantial research interest due to its involvement in various inflammatory disorders. Gouty arthritis (GA), a chronic inflammatory disease driven by the deposition of monosodium urate crystals, is characterized by a complex interplay between cell death pathways and inflammatory responses. Despite growing evidence linking ferroptosis to inflammatory regulation, its precise contribution to the onset and progression of GA remains unclear. This systematic review synthesizes current molecular insights into ferroptosis and examines its potential regulatory role in GA pathophysiology. By integrating recent experimental and clinical advances, it evaluates the therapeutic promise of targeting ferroptosis in GA. Through comprehensive analysis of ferroptosis-associated signaling networks and GA-related pathological events, this review aims to provide a stronger mechanistic foundation and highlight future directions for disease research and targeted therapeutic development.

Tophus is a hallmark lesion of chronic gout, formed through the combined effects of monosodium urate (MSU) crystal deposition, persistent inflammation, and progressive tissue fibrosis. These lesions can cause joint deformities, functional impairment, and renal damage, resulting in a significant decline in patients’ quality of life. Although hyperuricemia has traditionally been regarded as the primary cause of tophus formation, this explanation does not fully account for the considerable clinical heterogeneity observed among patients. In this study, we describe the multistage and dynamic pathological process underlying tophus formation. Building upon the foundation of hyperuricemia, the study focuses on MSU crystal nucleation, growth, and aggregation; crystal-triggered innate immune activation and NLRP3 inflammasome-mediated inflammatory cascades; the dual roles of neutrophil infiltration and neutrophil extracellular traps; macrophage phenotypic conversion, fibroblast activation, and extracellular matrix remodeling; the formation of multinucleated giant cells, complex cellular infiltration, and pathological angiogenesis; and the final formation of a mature, dense fibrous capsule structure. The study identifies the core regulatory nodes at each stage. Additionally, it explores potential therapeutic strategies for tophi and outlines future research directions. Together, these insights provide new therapeutic targets and a more comprehensive conceptual framework for early intervention and drug development. This research carries significant clinical and scientific value, with strong potential to improve outcomes for patients with chronic gout and to reduce the associated healthcare burden.

Gouty nephropathy is a common complication of gout, which is characterized pathologically by the abnormal deposition of urate crystals in the kidneys. This deposition can directly trigger local inflammatory responses and lead to renal tissue damage. Neutrophil extracellular traps (NETs), as a unique neutrophil-derived immune defense mechanism, play a key pro-inflammatory role in gouty nephropathy. Under conditions of long-term hyperuricemia, Monosodium urate (MSU) crystals can activate related inflammatory signaling pathways, promoting inflammatory cell infiltration, the release of pro-inflammatory factors, and the formation of NETs, thereby exacerbating inflammatory responses and fibrosis in hyperuricemic nephropathy. This review summarizes the formation and pro-inflammatory injury mechanisms of NETs in gouty nephropathy and discusses the potential and challenges of targeting NETs as a novel therapeutic strategy for gout-related kidney disease.

Gouty arthritis (GA) falls within the category of metabolic arthropathies. Its onset stems from abnormal uric acid metabolism, which subsequently leads to the deposition of monosodium urate (MSU) crystals and ultimately triggers a robust inflammatory response. Currently, the global prevalence rate of GA is on the rise, gradually increasing the societal disease burden it imposes. This review comprehensively examines the pathogenesis of GA. The content encompasses uric acid metabolic disorders, the innate immune activation process induced by MSU crystals, as well as various subsequently triggered programmed cell death (PCD) modalities, including pyroptosis, NETosis, apoptosis, necroptosis and ferroptosis. We then evaluate in vivo and in vitro experimental models according to the disease stage and pathogenic processes they best recapitulate. Exogenous MSU models are highly suitable for studying acute inflammatory flares; hyperuricemia models capture the metabolic basis of disease initiation; and composite models more closely reflect the chronic and multifactorial course of human gout. In vitro systems ranging from macrophage monocultures to co-culture and organoid platforms provide complementary tools for mechanistic studies and drug screening. However, current models still cannot fully reproduce the complexity of human gout, particularly with respect to metabolic initiation, tissue hierarchy, systemic context, and species-specific differences. We therefore propose a model-selection approach in which the choice of platform should be guided by the specific pathogenic process under investigation. Future model development should integrate innovative technologies to enhance the authenticity of pathological features, address the shortcomings of existing systems, and facilitate the clinical translation of GA research.