Investigation on the mechanism of action of Mailuoning in the treatment of acute kidney injury using network pharmacology

Yan Jiamin; Xie Leyi; Chen Bonian; Fan Jianhui; Li Ao

doi:10.13406/j.cnki.cyxb.003867

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Investigation on the mechanism of action of Mailuoning in the treatment of acute kidney injury using network pharmacology

Excellence in medical insights: traditional Chinese medicine pharmacology and diseases | 更新时间：2025-10-22

- Investigation on the mechanism of action of Mailuoning in the treatment of acute kidney injury using network pharmacology
- Journal of Chongqing Medical University Vol. 50, Issue 7, Pages: 870-878(2025)
- 作者机构：
  
  1.广东医科大学附属医院麻醉科，湛江 524001
  2.广东医科大学附属医院呼吸内科，湛江 524001
  3.广东医科大学附属医院临床研究实验中心，湛江 524001
- 作者简介：
- 基金信息：
- DOI：10.13406/j.cnki.cyxb.003867
  CLC： R285
- Received：12 April 2025，
  
  Revised：2025-05-15，
  
  Accepted：19 May 2025，
  
  Published：28 July 2025
- 稿件说明：
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严嘉敏,谢乐意,陈柏年,等.基于网络药理学探讨脉络宁治疗急性肾损伤的作用机制[J].重庆医科大学学报,2025,50(7):870-878.

Yan Jiamin,Xie Leyi,Chen Bonian,et al.Investigation on the mechanism of action of Mailuoning in the treatment of acute kidney injury using network pharmacology[J].Journal of Chongqing Medical University,2025,50(7):870-878.
严嘉敏,谢乐意,陈柏年,等.基于网络药理学探讨脉络宁治疗急性肾损伤的作用机制[J].重庆医科大学学报,2025,50(7):870-878. DOI： 10.13406/j.cnki.cyxb.003867.

Yan Jiamin,Xie Leyi,Chen Bonian,et al.Investigation on the mechanism of action of Mailuoning in the treatment of acute kidney injury using network pharmacology[J].Journal of Chongqing Medical University,2025,50(7):870-878. DOI： 10.13406/j.cnki.cyxb.003867.

摘要

目的

通过网络药理学方法，探讨脉络宁（mailuoning，MLN）对顺铂（cisplatin，CP）诱导的急性肾损伤（acute kidney injury，AKI）的保护作用，并分析其与抗凋亡途径相关的作用机制。

方法

通过网络药理学筛选MLN活性成分及AKI相关靶点：基于TCMSP和ETCM 2.0数据库获取MLN活性成分，利用Swiss Target Prediction预测成分靶点，结合GeneCards筛选AKI疾病靶点，取交集后通过STRING数据库构建蛋白-蛋白互作（protein-protein interaction，PPI）网络，Cytoscape拓扑分析筛选核心靶点，并对其进行基因本体（gene ontology，GO）功能注释及京都基因与基因组百科全书（kyoto encyclopedia of genes and genomes，KEGG）通路富集分析。动物实验：40只小鼠随机分为溶剂对照、MLN毒性对照、CP模型及CP+MLN组。MLN组以15 mL/（kg·d）腹腔注射MLN连续10 d；CP模型与CP+MLN组于第7天单次腹腔注射CP（20 mg/kg）。CP干预3 d后检测血浆尿素氮（blood urea nitrogen，BUN）及肌酐（creatinine，Cre）水平，苏木精-伊红（hematoxylin-eosin，HE）染色评估肾组织病理损伤，Western blot检测肾组织中中性粒细胞明胶酶相关脂质运载蛋白（neutrophil gelatinase-associated lipocalin，NGAL）及凋亡相关蛋白表达。

结果

网络药理学筛选得到104种MLN活性成分及224个作用靶点，AKI靶点2 465个，交集靶点117个，其中17个被认定为核心靶点。通过KEGG和GO分析发现，凋亡相关信号转导通路可能是MLN防治AKI的重要作用通路。动物实验结果证实成功构建了CP诱导的小鼠AKI模型，与CP模型组相比，MLN处理明显降低了血浆中BUN和Cre水平（

0.05），抑制了肾脏NGAL蛋白表达（

0.05），同时缓解了肾组织的病理学损伤。此外，MLN明显降低了AKI模型小鼠肾组织中p-P53（ser 15）、cleaved caspase-3蛋白的表达及Bax/Bcl-2蛋白表达量的相对比值（

0.05），同时上调蛋白激酶B（protein kinase B，AKT）磷酸化水平（

0.05）。

结论

MLN对CP诱导的小鼠AKI具有保护作用，其作用机制可能与其抗凋亡特性相关。

Abstract

Objective

To investigate the protective effects of Mailuoning（MLN） against cisplatin（CP）-induced acute kidney injury （AKI） utilizing network pharmacology and to analyze the underlying mechanism of action related to anti-apoptotic pathways.

Methods

Active components of MLN and targets related to AKI were identified using network pharmacology. The active components of MLN were sourced from the TCMSP and ETCM 2.0 databases. The targets of components were predicted using the Swiss Target Prediction tool，and subsequently the targets related to AKI were retrieved from the GeneCards database to identify intersecting targets. A protein-protein interaction network was constructed using the STRING database，and a topological analysis was performed using Cytoscape to identify core targets. Gene Ontology（GO） functional annotation and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analyses were conducted on these core targets. For the animal experiments，forty mice were randomly assigned to four groups： solvent control，MLN toxicity control，CP model，and CP+MLN groups. The MLN group received intraperitoneal injections of MLN at a dose of 15 mL/（kg·d） for ten consecutive days. The CP model and CP+MLN groups were administered a single intraperitoneal injection of CP at 20 mg/kg on day 7. Three days after the CP treatment，plasma levels of blood urea nitrogen（BUN） and creatinine（Cre） were measured. The pathological injury of kidney tissues was assessed using hematoxylin-eosin staining. Western blot analysis was utilized to determine the expression of neutrophil gelatinase-associated lipocalin（NGAL） and apoptosis-related proteins in kidney tissues.

Results

A total of 104 active components of MLN and 224 targets were identified using network pharmacology，and 2 465 targets were identified to be related to AKI，resulting in 117 intersecting targets，of which，17 targets were classified as core targets. KEGG and GO analyses indicated that the apoptosis-related signal transduction pathway might be a crucial pathway through which MLN provided protective effects against AKI. The results of animal experiments confirmed the successful establishment of CP-induced AKI models in mice. Compared with the CP model group，MLN treatment significantly reduced plasma levels of BUN and Cre（

0.05），inhibited NGAL protein expression in the kidneys（

0.05），and improved the pathological injury observed in kidney tissues. Furthermore，MLN markedly reduced the expression levels of p-P53（ser 15） and cleaved caspase-3 proteins，as well as the Bax/Bcl-2 ratio in kidney tissues of AKI model mice（

0.05），while upregulating protein

kinase B phosphorylation levels（

0.05）.

Conclusion

MLN demonstrates protective effects against CP-induced AKI in mice，potentially through mechanisms related to its anti-apoptotic properties.

关键词

Keywords

references

Raji-Amirhasani A ， Khaksari M ， Mahani FD ， et al . Activators of SIRT1 in the kidney and protective effects of SIRT1 during acute kidney injury （AKI）（effect of SIRT1 activators on acute kidney injury） [J ] . Clin Exp Nephrol ， 2021 ， 25 （ 8 ）： 807 - 821 ．

Wang D ， Lippard SJ . Cellular processing of platinum anticancer drugs [J ] . Nat Rev Drug Discov ， 2005 ， 4 （ 4 ）： 307 - 320 ．

Hamroun A ， Lenain R ， Bigna JJ ， et al . Prevention of cisplatin-induced acute kidney injury：a systematic review and meta-analysis [J ] . Drugs ， 2019 ， 79 （ 14 ）： 1567 - 1582 ．

朱媛媛，杨梦霞，李新民 . 中药预防顺铂肾毒性的Meta分析 [J ] . 中国中医药现代远程教育， 2019 ， 17 （ 10 ）： 60 - 63 ．

Zhu YY ， Yang MX ， Li XM . Meta analysis on Chinese medicine in the prevention of cisplatin-induced renal toxicity [J ] . Chin Med Mod Distance Educ China ， 2019 ， 17 （ 10 ）： 60 - 63 ．

陈坚，湛苑聆 . 活血化瘀方对急性肾损伤患者肾功能的改善作用 [J ] . 中国卫生标准管理， 2021 ， 12 （ 6 ）: 125 - 127 .

Chen J ， Zhan YL . Application Effect of Chinese medicine for promoting blood circulation and removing blood stasis in patients with acute kidney injury and its improvement on renal function indexes [J ] . China Health Standard Management ， 2021 ， 12 （ 6 ）： 125 - 127 .

崔向君，陈加敏，孔立，等 . 中医药治疗脓毒症相关急性肾损伤的研究进展 [J ] . 中国中医急症， 2024 ， 33 （ 9 ）： 1685 - 1688 .

Cui XJ ， Chen JM ， Kong L ， et al . Research progress on traditional Chinese medicine in the treatment of sepsis-associated acute kidney injury [J ] . Journal of Emergency Medicine in TCM ， 2024 ， 33 （ 9 ）： 1685 - 1688 .

董玉岗，汪妍，韩燕 . 活血化瘀解毒方对重症胰腺炎合并急性肾损伤大鼠相关炎症因子、Bax及Bcl-2表达的影响 [J ] . 中国中医急症， 2021 ， 30 （ 7 ）： 1174 - 1178 .

Dong YG ， Wang Y ， Han Y . Effect of Huoxue Huayu Jiedu decoction on expression of related inflammatory factors，Bax and Bcl-2 in rats with severe pancreatitis and acute kidney injury [J ] . Journal of Emergency Medicine in TCM ， 2021 ， 30 （ 7 ）： 1174 - 1178 .

李语玲，杨　静 . 脉络宁注射液对下肢动脉硬化闭塞症大鼠血管内皮功能及NF-κB介导炎症反应的影响 [J ] . 中南药学， 2020 ， 18 （ 10 ）： 1677 - 1680 ．

Li YL ， Yang J . Effect of Mailuoning injection on vascular endothelial function and inflammatory response mediated by NF-κB in rats with lower extremity arteriosclerosis obliterans [J ] . Cent South Pharm ， 2020 ， 18 （ 10 ）： 1677 - 1680 ．

张淑波，张　玲，祝亮，等 . 脉络宁注射液联合贝那普利治疗慢性肾小球肾炎临床观察 [J ] . 中华中医药学刊， 2017 ， 35 （ 11 ）： 2950 - 2952 ．

Zhang SB ， Zhang L ， Zhu L ， et al . Clinical observation of mailuoning injection combined with benazepril in treatment of chronic glomerulonephritis [J ] . Chin Arch Tradit Chin Med ， 2017 ， 35 （ 11 ）： 2950 - 2952 ．

邱　欣，唐银霏，陈新政，等 . 脉络宁注射液联合环磷酰胺对慢性肾小球肾炎患者血液流变学、肾功能、PAI-1及t-PA的影响 [J ] . 长春中医药大学学报， 2019 ， 35 （ 2 ）： 267 - 269 ．

Qiu X ， Tang YF ， Chen XZ ， et al . Effect of mailuoning injection combined with cyclophosphamide on blood rheology，renal function，PAI-1 and t-PA in patients with chronic glomerulonephritis [J ] . J Changchun Univ Chin Med ， 2019 ， 35 （ 2 ）： 267 - 269 ．

陈翠强，陈兴强，陈　洁，等 . 脉络宁颗粒联合贝那普利治疗慢性肾小球肾炎的疗效及对外周血IL-4、IL-10、INF-γ、TAFI的影响 [J ] . 中药材， 2020 ， 43 （ 2 ）： 486 - 489 ．

Chen CQ ， Chen XQ ， Chen J ， et al . Effect of Mailuoning Granule combined with Benazepril on chronic glomerulonephritis and its influence on IL-4，IL-10，INF-γ and TAFI in peripheral blood [J ] . J Chin Med Mater ， 2020 ， 43 （ 2 ）： 486 - 489 ．

何秀芳，谭诚成，李圣永 . 脉络宁注射液通过Akt信号通路降低Hcy诱导的ECV304细胞损伤的实验研究 [J ] . 中西医结合心脑血管病杂志， 2022 ， 20 （ 6 ）： 1003 - 1007 ．

He XF ， Tan CC ， Li SY . Effects of mailuoning injection on ECV304 cell injury induced by hcy through Akt signal pathway [J ] . Chin J Integr Med Cardio Cerebrovasc Dis ， 2022 ， 20 （ 6 ）： 1003 - 1007 ．

Ren D ， Shen ZY ， Qin LP ， et al . Pharmacology，phytochemistry，and traditional uses of Scrophularia ningpoensis Hemsl [J ] . J Ethnopharmacol ， 2021 ， 269 ： 113688 ．

Wang Y ， Yuan Y ， Wang WT ， et al . Mechanisms underlying the therapeutic effects of Qingfeiyin in treating acute lung injury based on GEO datasets，network pharmacology and molecular docking [J ] . Comput Biol Med ， 2022 ， 145 ： 105454 ．

Miao JQ ， Shen J ， Yan CQ ， et al . The protective effects of Mai-Luo-Ning injection against LPS-induced acute lung injury via the TLR4/NF-κB signalling pathway [J ] . Phytomedicine ， 2022 ， 104 ： 154290 ．

Kim JY ， Jo J ， Leem J ， et al . Kahweol ameliorates cisplatin-induced acute kidney injury through pleiotropic effects in mice [J ] . Biomedicines ， 2020 ， 8 （ 12 ）： 572 ．

Hu JQ ， Gu WJ ， Ma N ， et al . Leonurine alleviates ferroptosis in cisplatin-induced acute kidney injury by activating the Nrf2 signalling pathway [J ] . Br J Pharmacol ， 2022 ， 179 （ 15 ）： 3991 - 4009 ．

Zhang YP ， Chen YE ， Li BX ， et al . The effect of monotropein on alleviating cisplatin-induced acute kidney injury by inhibiting oxidative damage，inflammation and apoptosis [J ] . Biomed Pharmacother ， 2020 ， 129 ： 110408 ．

武周游，李　婷，张腾伟，等 . miR-370-3p/SESN2调控脂多糖诱导的小鼠肺泡上皮细胞凋亡的机制研究 [J ] . 重庆医科大学学报， 2024 ， 49 （ 9 ）： 1121 - 1128 ．

Wu ZY ， Li T ， Zhang TW ， et al . Mechanism of miR-370-3p/SESN2 regulating lipopolysaccharide-induced apoptosis of mouse alveolar epithelial cells [J ] . J Chongqing Med Univ ， 2024 ， 49 （ 9 ）： 1121 - 1128 ．

Palm CA ， Segev G ， Cowgill LD ， et al . Urinary neutrophil gelatinase-associated lipocalin as a marker for identification of acute kidney injury and recovery in dogs with gentamicin-induced nephrotoxicity [J ] . J Vet Intern Med ， 2016 ， 30 （ 1 ）： 200 - 205 ．

Jiang M ， Wang CY ， Huang S ， et al . Cisplatin-induced apoptosis in p53-deficient renal cells via the intrinsic mitochondrial pathway [J ] . Am J Physiol Renal Physiol ， 2009 ， 296 （ 5 ）： 983 - 993 ．

Miao NJ ， Wang B ， Xu D ， et al . Caspase-11 promotes cisplatin-induced renal tubular apoptosis through a caspase-3-dependent pathway [J ] . Am J Physiol Renal Physiol ， 2018 ， 314 （ 2 ）： 269 - 279 ．

Zhu H ， Jiang WJ ， Zhao HZ ， et al . PSTPIP2 inhibits cisplatin-induced acute kidney injury by suppressing apoptosis of renal tubular epithelial cells [J ] . Cell Death Dis ， 2020 ， 11 （ 12 ）： 1057 ．

Zhu SQ ， Huo LL ， Zeng J ， et al . Differentiated management of ROS level in tumor and kidney to alleviate Cis -platinum induced acute kidney injury with improved efficacy [J ] . J Nanobiotechnology ， 2024 ， 22 （ 1 ）： 436 ．

Zhou M ， Dai YP ， Ma Y ， et al . Protective effects of liquiritigenin against cisplatin-induced nephrotoxicity via NRF2/SIRT3-mediated improvement of mitochondrial function [J ] . Molecules ， 2022 ， 27 （ 12 ）： 3823 ．

Fan LL ， Tang K ， Li J ， et al . Mailuoning oral liquid ameliorates vasculitis in thromboangiitis obliterans rats via inactivating cGAS-STING-IRF3 and TLR4-MAPKs/NF-κB signaling pathways [J ] . J Ethnopharmacol ， 2025 ， 337 （ Pt 1 ）： 118707 ．

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