Tangshen Guanchang(糖肾灌肠)Prescription Reduces Inflammation in Diabetic Kidney Disease via Regulating PI3K/AKT/NF-κB Signaling Pathway
Objective:Diabetic kidney disease(DKD)is a chronic kidney disease caused by hyperglycemia,in which inflammation plays a key role.Tangshen Guanchang(糖肾灌肠)Prescription is effective in the treatment of DKD,the mechanism of which,however,remains un-clear.To decipher the mechanism of Tangshen Guanchang Prescription in the treatment of DKD by animal experiment,clinical trial,network pharmacology,and molecular docking.Methods:Sixty C57 mice were randomized into normal control,model control,canagliflozin(0.013 g/kg),and Tangshen Guanchang Prescription(52 g/kg)groups.The mouse model of DKD was induced by a high-glucose and high-fat diet combined with intraperitoneal injection of streptozotocin(STZ).The successfully modeled mice were administrated with corre-sponding drugs for 28 consecutive days.The pathological changes in the renal tissue of DKD mice were observed by hematoxylin-eosin(HE)staining.The mRNA and protein levels of phosphatidylinositol 3-kinase(Pi3k),protein kinase B(Akt),nuclear factor-kappa B(Nfκb),tumor necrosis factor(Tnf)-α,and interleukin(Il)-6 in the renal tissue were determined by RT-qPCR and Western blotting,respectively.Furthermore,40 DKD patients meeting the inclusion criteria were randomized into a control group(n=20)and an observation group(n=20),and other 20 healthy volunteers(physical examination)were included as the normal control group.The control group was treated with Western medicine(routine treatment),and the observation group with Tangshen Guanchang Prescription on the basis of routine treatment.After two weeks of treatment,the levels of microalbumin(mALB),urinary albumin-to-creatinine ratio(UACR),M1 macrophages,TNF-α,and IL-6 were compared between the two groups.With the herbal names in Tangshen Guanchang Prescription and"diabetic kidney disease"as keywords,the relevant databases were searched for network pharmacology and molecular docking.Results:The animal experiments showed that compared with the normal control group,the model control group presented aggravated pathological injuries and up-regulated mR-NA and protein levels of Pi3k,Akt,NfKb,Tnf-α,and Il-6 in the renal tissue(P＜0.01).Compared with the model control group,Tangshen Guanchang Prescription(52 g/kg)mitigated the pathological injuries and down-regulated the mRNA and protein levels of Pi3k,Akt,NfKb,Tnf-α,and Il-6(P＜0.01).The clinical trial showed that after treatment,the observation group demonstrated more significant decreases in mALB,UACR,M1 macrophages,TNF-α,and IL-6 than the control group(P＜0.01).The network pharmacology predicted 118 active com-ponents(including aloe-emodin and karanjin)in Tangshen Guanchang Prescription,and the core targets included TNF-α and IL-6.Gene Ontology(GO)enrichment showcased that the targets involved biological processes such as inflammation,molecular functions such as specif-ic binding to protein domains,and cell components such as extracellular space.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrich-ment showed that PI3K/AKT signaling pathways played a key role in the treatment of DKD with Tangshen Guanchang Prescription.Conclu-sion:Tangshen Guanchang Prescription may reduce inflammation in DKD by regulating the expression of PI3K/AKT/NF-κB signaling path-way and the release of inflammatory cytokines such as TNF-α and IL-6.
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