Qingshen Granules improves renal function of patients with chronic kidney disease damp-heat syndrome by activating the miR-23b and Nrf2 pathway

doi:10.12122/j.issn.1673-4254.2025.09.07

Abstract

Abstract:

Objective To investigate the therapeutic mechanism of Qingshen Granules (QSG) in patients with chronic kidney disease (CKD) damp-heat syndrome. Methods The regulatory targets of QSG were retrieved and mapped using TCMSP and UniProt. Small RNA sequencing technology was used to screen the target genes of chronic renal failure damp-heat syndrome to construct the "active ingredients-intersection targets-diseases" network, followed by KEGG pathway enrichment analysis and molecular docking of the core targets. Sixty patients with CKD (stage 3-5) presenting with damp-heat syndrome and not undergoing dialysis were randomized equally into two groups for conventional Western medicine treatment (control group) and additional treatment with QSG (observation group) for 8 weeks, with 20 healthy individuals as the normal control group. The expression levels of miR-23b-5p, Nrf2 and HO-1 protein in peripheral blood mononuclear cells (PBMC), renal function indicators (Scr and eGFR), and serum ROS, AOPP and PON-1 levels were compared among the 3 groups after the treatments. Results Six main active ingredients of QSG were identified, and their key targets included ACTB, JUN, PTEN, ESR1, GSK3B, PPARG, PIK3CA, APP, PIK3R1, and BECN1. MiR-23b-5p expression was significantly up-regulated in CKD damp-heat syndrome, in which the Nrf2 pathway abnormality played an important pathogenic role. Molecular docking results suggested good binding activity of the core targets with the active ingredients of QSG, and NFE2L2 had the strongest binding with luteolin. In patients with CKD damp-heat syndrome, QSG treatment significantly decreased serum Scr, ROS and AOPP levels, obviously improved eGFR, and increased serum PON-1 levels, expression levels of Nrf2 and HO-1 proteins in PBMCs, and the expression level of miR-23b-5p. Conclusion QSG can improve the renal function in patients with CKD damp-heat syndrome possibly by up-regulating miR-23b expression, activating the Nrf2 antioxidant pathway, and reducing oxidative stress levels.

Key words: Qingshen Granules, chronic kidney disease, microRNA, Nrf2 pathway, network pharmacology

Qin HU, Hua JIN. Qingshen Granules improves renal function of patients with chronic kidney disease damp-heat syndrome by activating the miR-23b and Nrf2 pathway[J]. Journal of Southern Medical University, 2025, 45(9): 1867-1879.

Figures/Tables 18

References 29

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Group	Age (year)	Course	Gender		CKD staging			Underlying medical conditions
Group	Age (year)	Course	Male	Female	3	4	5	Chronic nephritis	Hypertension	Diabetes	Polycystic kidney disease
Normal (n=20)	51.55±8.17	-	11	9	-	-	-	-		-	-	-
Control (n=30)	48.73±9.13	3.74±1.92	17	13	1	17	12	12		7	7	4
Observation (n=30)	50.03±9.64	3.91±2.04	16	14	5	11	14	10		8	8	4

Group	Age (year)	Course	Gender		CKD staging			Underlying medical conditions
Group	Age (year)	Course	Male	Female	3	4	5	Chronic nephritis	Hypertension	Diabetes	Polycystic kidney disease
Normal (n=20)	51.55±8.17	-	11	9	-	-	-	-		-	-	-
Control (n=30)	48.73±9.13	3.74±1.92	17	13	1	17	12	12		7	7	4
Observation (n=30)	50.03±9.64	3.91±2.04	16	14	5	11	14	10		8	8	4

miRNA_id	log2 Fold Change	qValue	Regulation
hsa-let-7b-3p	8.206372	1.35×10^-5	Up
hsa-let-7f-2-3p	9.086326	0.0016	Up
……	……	……	……
hsa-miR-20a-5p	10.3875	1.37×10^-5	Up
hsa-miR-21-5p	5.334294	0.000371	Up
hsa-miR-23b-5p	-4.50953	0.003782	Down
hsa-miR-26b-5p	4.938481	0.003172	Up
hsa-miR-27a-3p	4.084065	0.005144	Up
hsa-miR-30d-3p	-2.49269	0.049808	Down

miRNA_id	log2 Fold Change	qValue	Regulation
hsa-let-7b-3p	8.206372	1.35×10^-5	Up
hsa-let-7f-2-3p	9.086326	0.0016	Up
……	……	……	……
hsa-miR-20a-5p	10.3875	1.37×10^-5	Up
hsa-miR-21-5p	5.334294	0.000371	Up
hsa-miR-23b-5p	-4.50953	0.003782	Down
hsa-miR-26b-5p	4.938481	0.003172	Up
hsa-miR-27a-3p	4.084065	0.005144	Up
hsa-miR-30d-3p	-2.49269	0.049808	Down

Key ingredients	Target	Affinity (kcal/mol)
	ACTB	-2.88
	PTEN	-2.55
Quercetin	PPARG	-5.31
	PIK3CA	-4.9
Kaempferol Apigenin Luteolin	NFE2L2 ACTB PTEN PPARG PIK3CA NFE2L2 ACTB PTEN PPARG PIK3CA NFE2L2 ACTB PTEN PPARG PIK3CA NFE2L2	-4.8 -3.61 -3.5 -4.1 -2.63 -4.96 -3.21 -2.34 -4.13 -4.05 -6.0 -4.34 -3.58 -4.26 -4.19 -5.38