The First Clinical Medicine School, Guangzhou University of Chinese Medicine, Guangzhou 510405, China; Department of Rheumatology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
The First Clinical Medicine School, Guangzhou University of Chinese Medicine, Guangzhou 510405, China; Department of Rheumatology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
Int Immunopharmacol. 2022 Oct;111:109112. doi: 10.1016/j.intimp.2022.109112. Epub 2022 Aug 3.
Quercetin is widely found in natural plants, especially Chinese herbal plants. It has been used to treat arthritis in China for thousands of years. However, the effects and mechanisms of quercetin in the treatment of gout arthritis (GA) remain unclear. We aimed to verify the treatment of GA with quercetin and investigate the underlying mechanism. A combination of network pharmacology and experiments was used to reveal the mechanism of quercetin in the treatment of GA. Potential targets of quercetin and gout were identified. Then, the protein-protein interaction network for the common targets between quercetin and gout was constructed and the core targets were identified. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses for the common targets were performed to elucidate the pharmacological functions and mechanisms associated with quercetin treatment in GA. Finally, a monosodium urate-induced GA rat model was used to validate the predicted mechanisms in network pharmacology. Seventy-two common targets were identified. KEGG analysis revealed that treatment of GA with quercetin predominantly involved the interleukin (IL)-17, tumor necrosis factor (TNF), mitogen-activated protein kinase, and phosphoinositide 3-kinase-Akt signaling pathways. In an experimental validation, quercetin attenuated ankle joint inflammation-induced bone destruction and histological lesions. It also diminished the expression of IL-6, IL-17A, and IL-17F in the IL-17 pathway, and regulated the release of RAR-related orphan receptor gamma t,IL-17E, IL-1β, IL-6, TNF-α, Foxp3, and transforming growth factor-beta 1. The collective findings implicate quercetin as a valuable alternative drug for the treatment of GA.
槲皮素广泛存在于天然植物中,特别是中草药植物中。在中国,它已经被用于治疗关节炎几千年了。然而,槲皮素在治疗痛风性关节炎(GA)中的作用和机制尚不清楚。我们旨在验证槲皮素治疗 GA 的效果,并探讨其潜在的作用机制。本研究采用网络药理学和实验相结合的方法来揭示槲皮素治疗 GA 的作用机制。鉴定出槲皮素和痛风的潜在靶点。然后,构建了槲皮素和痛风共同靶点的蛋白质-蛋白质相互作用网络,并鉴定出核心靶点。对共同靶点进行基因本体论和京都基因与基因组百科全书(KEGG)分析,以阐明与槲皮素治疗 GA 相关的药理功能和机制。最后,建立了尿酸钠诱导的 GA 大鼠模型来验证网络药理学预测的机制。鉴定出 72 个共同靶点。KEGG 分析表明,槲皮素治疗 GA 主要涉及白细胞介素(IL)-17、肿瘤坏死因子(TNF)、丝裂原活化蛋白激酶和磷酸肌醇 3-激酶-蛋白激酶 B(PI3K-Akt)信号通路。在实验验证中,槲皮素减轻了踝关节炎症引起的骨破坏和组织学损伤。它还降低了 IL-17 通路中 IL-6、IL-17A 和 IL-17F 的表达,并调节 RAR 相关孤儿受体γ t、IL-17E、IL-1β、IL-6、TNF-α、Foxp3 和转化生长因子-β 1 的释放。这些发现表明槲皮素是治疗 GA 的一种有价值的替代药物。