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Network Pharmacology and Molecular Docking Analysis to Explore the Mechanism of Huaiqihuang-Mediated Alleviation of Henoch–Schönlein Purpura Nephritis
BioMed Research International ( IF 2.6 ) Pub Date : 2022-11-4 , DOI: 10.1155/2022/2798217
Qingqing Liu 1 , Jiahua Liu 2 , Yaya Du 1 , Weiyan Guo 3 , Jie Mi 4 , Yanyan Guo 1
Affiliation  

Objective. Henoch–Schönlein purpura nephritis (HSPN) is considered a major cause of chronic renal failure and is the most common secondary glomerular disease in children. Huaiqihuang (HQH), a traditional Chinese herbal formula, exhibits therapeutic effects against HSPN in clinical practice. However, the potential molecular targets and mechanisms underlying HSPN treatment remain unclear. Methods. By constructing a protein-protein interaction (PPI) network, core targets related to HQH and HSPN were identified. Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathways were analyzed to identify the main pathways related to HSPN based on the core targets. To screen the main active ingredients of HQH against HSPN, an ingredient-target-pathway network was constructed using the top 10 main pathways associated with HSPN. Then, molecular docking was performed to explore the interactions and binding patterns between molecules and proteins. Results. Clinical data showed that HQH combined with conventional medicine significantly reduced 24-hour urine protein excretion, urine microalbumin levels, and erythrocyte counts in the urine sediment of HSPN patients. By constructing PPI models, 15 potential core targets were identified. The top 10 main pathways showed higher enrichment ratios, including the cytokine–cytokine receptor interaction and signaling pathways related to NOD-like receptor, IL-17, etc. Through the ingredient-target-pathway network and molecular docking, we revealed that five active ingredients of HQH had good affinities with three core targets, AKT1, MMP9, and SERPINE1, which may be vital in treating HSPN. Conclusions. The study preliminarily explored the active ingredients, targets, and pathways involved in HQH therapy for HSPN. The mechanism of HQH therapy may be attributed to the modulation of inflammatory response, immune response, and oxidative stress. Combined with clinical data, our results indicate that HQH is highly effective in treating HSPN.

中文翻译:

网络药理学和分子对接分析探讨槐芪黄介导的过敏性紫癜性肾炎的缓解机制

目标。过敏性紫癜性肾炎 (HSPN) 被认为是慢性肾功能衰竭的主要原因,是儿童中最常见的继发性肾小球疾病。槐杞黄 (HQH) 是一种传统的中草药配方,在临床实践中对 HSPN 具有治疗作用。然而,HSPN 治疗的潜在分子靶点和机制仍不清楚。方法. 通过构建蛋白质-蛋白质相互作用 (PPI) 网络,确定了与 HQH 和 HSPN 相关的核心靶点。分析了基因本体富集和京都基因百科全书和基因组通路,以基于核心目标识别与 HSPN 相关的主要通路。为了针对 HSPN 筛选 HQH 的主要活性成分,使用与 HSPN 相关的前 10 条主要途径构建了成分-靶点-途径网络。然后,进行分子对接以探索分子与蛋白质之间的相互作用和结合模式。结果. 临床数据显示,HQH 联合常规药物可显着降低 HSPN 患者的 24 小时尿蛋白排泄量、尿微量白蛋白水平和尿沉渣中的红细胞计数。通过构建 PPI 模型,确定了 15 个潜在的核心目标。前 10 条主要通路富集率较高,包括细胞因子-细胞因子受体相互作用以及与 NOD 样受体、IL-17 等相关的信号通路。通过成分-靶点-通路网络和分子对接,我们揭示了 5 个活性HQH 的成分与三个核心靶点 AKT1、MMP9 和 SERPINE1 具有良好的亲和力,这可能对治疗 HSPN 至关重要。结论. 该研究初步探索了 HQH 治疗 HSPN 所涉及的活性成分、靶点和通路。HQH 治疗的机制可能归因于炎症反应、免疫反应和氧化应激的调节。结合临床数据,我们的结果表明 HQH 对治疗 HSPN 非常有效。
更新日期:2022-11-04
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