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基于网络药理学的策略研究无多糖提取物治疗慢性肾脏病的药理机制并在动物模型中进行验证

Network pharmacology-based strategy to investigate pharmacological mechanisms of polysaccharide-free extract for chronic kidney disease treatment and verification in an animal model.

作者信息

Liu Meiyou, Gao Kai, Cui Jia, Wu Xiaoxiao, Ding Likun, Fan Tingting, Zhang Juanli, Zhang Di, Ren Danjun, Wen Aidong, Wang Jingwen

机构信息

Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

出版信息

Ren Fail. 2025 Dec;47(1):2539942. doi: 10.1080/0886022X.2025.2539942. Epub 2025 Jul 31.

DOI:10.1080/0886022X.2025.2539942
PMID:40744909
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12315129/
Abstract

(LBP) have shown renal protection effects. However, research on other active components of extract (ELB) for the therapy of chronic kidney disease (CKD) is limited. This study aims to investigate the renoprotective effects and molecular mechanisms of ELB in CKD. ELB was extracted from fruits using 85% ethanol reflux, followed by vacuum concentration and sequential extraction to remove polysaccharides. Chemical components and target genes were identified using TCMSP and UniProt databases, followed by pharmacology network construction and GO/KEGG pathway analysis. A 5/6 nephrectomy model in Sprague-Dawley rats was used to study the renoprotective effects of ELB, with H&E staining and biochemical analyses. Western blot analysis assessed IL-6 and VEGF expression in renal tissues. Chemical analysis of ELB identified 188 components, with 45 meeting screening criteria, and 34 linked to 94 target genes. The intersection with CKD-related genes yielded 39 overlapping genes, with quercetin having the most targets. GO/KEGG pathway analyses highlighted significant biological processes and pathways. A PPI network identified IL-6, VEGFA, CASP3, EGFR, ESR1, and PPARG as hub genes. In a 5/6 nephrectomy rat model, ELB treatment significantly reduced renal damage, serum BUN and SCr levels, as well as IL-6 and VEGF expression in renal tissues, validating its renoprotective effects and supporting bioinformatics predictions. This work identified the intricate components and pharmacological actions of ELB, which is devoid of LBP. The findings preliminarily confirm the potential of ELB as a novel therapeutic agent for preventing and managing CKD.

摘要

(LBP)已显示出肾脏保护作用。然而,提取物(ELB)的其他活性成分用于治疗慢性肾脏病(CKD)的研究有限。本研究旨在探讨ELB在CKD中的肾脏保护作用及其分子机制。采用85%乙醇回流法从果实中提取ELB,然后进行真空浓缩和顺序萃取以去除多糖。利用TCMSP和UniProt数据库鉴定化学成分和靶基因,随后构建药理网络并进行GO/KEGG通路分析。采用Sprague-Dawley大鼠5/6肾切除模型研究ELB的肾脏保护作用,进行苏木精-伊红染色和生化分析。蛋白质印迹分析评估肾组织中IL-6和VEGF的表达。对ELB的化学分析鉴定出188种成分,其中45种符合筛选标准,34种与94个靶基因相关。与CKD相关基因的交集产生39个重叠基因,槲皮素的靶标最多。GO/KEGG通路分析突出了显著的生物学过程和通路。蛋白质-蛋白质相互作用网络确定IL-6、VEGFA、CASP3、EGFR、ESR1和PPARG为枢纽基因。在5/6肾切除大鼠模型中,ELB治疗显著减轻了肾脏损伤、血清尿素氮和血肌酐水平,以及肾组织中IL-6和VEGF的表达,验证了其肾脏保护作用并支持生物信息学预测。这项工作确定了不含LBP的ELB的复杂成分和药理作用。这些发现初步证实了ELB作为预防和管理CKD的新型治疗药物的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aab/12315129/151a38f99667/IRNF_A_2539942_F0005_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aab/12315129/67e600f48a18/IRNF_A_2539942_F0001_B.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aab/12315129/df19b87dc529/IRNF_A_2539942_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aab/12315129/151a38f99667/IRNF_A_2539942_F0005_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aab/12315129/67e600f48a18/IRNF_A_2539942_F0001_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aab/12315129/9b10f22d7353/IRNF_A_2539942_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aab/12315129/3aa1c24840ec/IRNF_A_2539942_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aab/12315129/df19b87dc529/IRNF_A_2539942_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aab/12315129/151a38f99667/IRNF_A_2539942_F0005_B.jpg

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