Study on Mechanism of Modified Guizhi Fuling Pills in Treating Diabetic Kidney Disease through Autophagy Regulation
10.19879/j.cnki.1005-5304.202503286
- VernacularTitle:加味桂枝茯苓丸通过调控自噬治疗糖尿病肾病的作用机制研究
- Author:
Ziying LIU
1
;
Jinhong LENG
;
Xiaochen WEN
;
Aihua LIU
;
Xinyu SUN
;
Changxin MIAO
;
Yongming LIU
Author Information
1. 辽宁中医药大学,辽宁 沈阳 110847
- Publication Type:Journal Article
- Keywords:
modified Guizhi Fuling Pills;
diabetic nephropathy;
autophagy;
network pharmacology;
animal experiment
- From:
Chinese Journal of Information on Traditional Chinese Medicine
2025;32(8):46-55
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the mechanism of modified Guizhi Fuling Pills in treating diabetic kidney disease(DKD)through autophagy regulation based on network pharmacology and experimental validation.Methods Active components and action targets of modified Guizhi Fuling Pills were screened via the TCMSP database.DKD-related autophagy targets were obtained from GeneCards,TTD,DrugBank and PharmGKB.A protein-protein interaction network was constructed using STRING,followed by GO functional and KEGG pathway enrichment analyses via DAVID.Molecular docking of key components and core targets was performed using AutoDock Tools 1.5.7.DKD model rats were prepared.The rats were randomly divided into normal group,model group,valsartan group(50 mg/kg),and modified Guizhi Fuling Pills low-,medium-and high-dosage group(9.9,19.8 and 39.6 g/kg).After 8-week interventions,body mass and water intake were recorded;fasting blood glucose,24 h urinary total protein(24 hUTP),urinary albumin-to-creatinine ratio(UACR)were monitored.Renal histopathology was evaluated via HE and Masson staining.Western blot was used to detect protein expressions of AMPK/FOXO1 pathway(p-AMPK,AMPK,FOXO1)and autophagy markers(Beclin-1,p62),while quantitative real-time PCR was used to assess AMPK and FOXO1 mRNA expressions.Results A total of 146 active components of Guizhi Fuling Pills and 33 main targets for treating DKD were screened,with the core targets including FOXO1,BCL2,TP53 and PTEN.KEGG pathway enrichment analysis suggested that AMPK/FOXO1 signaling pathway,AGE-RAGE and insulin signaling pathways may play a core regulatory role.Guizhi Fuling Pills could significantly reduce the body mass of DKD rats,reduce water intake,decrease renal index,decrease fasting blood glucose,24 hUTP and UACR(P<0.05,P<0.01),improve renal tissue pathology,increase AMPK,FOXO1,Beclin-1 protein expressions and AMPK,FOXO1 mRNA expressions(P<0.05),and reduce p62 protein expression(P<0.05).Conclusion Modified Guizhi Fuling Pills may exert therapeutic effects on DKD by regulating the AMPK-FOXO1-autophagy axis.
