Investigation on the mechanism of action of Mailuoning in the treatment of acute kidney injury using network pharmacology
10.13406/j.cnki.cyxb.003867
- VernacularTitle:基于网络药理学探讨脉络宁治疗急性肾损伤的作用机制
- Author:
Jiamin YAN
1
;
Leyi XIE
;
Bonian CHEN
;
Jianhui FAN
;
Ao LI
Author Information
1. 广东医科大学附属医院麻醉科,湛江 524001
- Keywords:
network pharmacology;
Mailuoning;
cisplatin;
acute kidney injury;
anti-apoptosis
- From:
Journal of Chongqing Medical University
2025;50(7):870-878
- CountryChina
- Language:Chinese
-
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 en-richment 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 injec-tion 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 as-sessed using hematoxylin-eosin staining.Western blot analysis was utilized to determine the expression of neutrophil gelatinase-associated lipocalin(NGAL)and apoptosis-related proteins in kid-ney 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(P<0.05),inhibited NGAL protein expression in the kidneys(P<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(P<0.05),while upregulating protein kinase B phosphorylation levels(P<0.05).Conclusion:MLN demonstrates protective effects against CP-induced AKI in mice,potentially through mechanisms related to its anti-apoptotic properties.
