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pmid:40606302

Yiqi Yangyin Tongluo Recipe Alleviates Diabetic Kidney Disease Through AGE-RAGE Signalling Axis.

Rucui Yu · Ruiying Wu · Tingting Chen · Yan Zhang · Xiangqing Chen

Diabetes, metabolic syndrome and obesity : targets and therapy · 2025 doi:10.2147/DMSO.S523784

Paper

complete

Experiment

complete

Data

partial

Analysis

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Execution

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title
Yiqi Yangyin Tongluo Recipe Alleviates Diabetic Kidney Disease Through AGE-RAGE Signalling Axis.
doi
10.2147/DMSO.S523784
pmid
40606302
authors array · 5 items
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Rucui Yu
[1]
Ruiying Wu
[2]
Tingting Chen
[3]
Yan Zhang
[4]
Xiangqing Chen
journal
Diabetes, metabolic syndrome and obesity : targets and therapy
year
2025
abstract
Purpose: This study used network pharmacology to explore how Yiqi Yangyin Tongluo Formula (YQYTLF) alleviates diabetic nephropathy (DN), focusing on the AGE-RAGE signaling pathway. Methods: Active compounds and targets of YQYTLF were identified via TCMSP, and a herb-compound-target network was constructed using Cytoscape. Differentially expressed genes from DN kidney tissues (GEO dataset GSE104948) were intersected with drug targets for KEGG and GO enrichment analysis. Protein-protein interaction (PPI) networks were analyzed in STRING and visualized in Cytoscape. A DN rat model was treated with YQYTLF, with weekly monitoring of body weight, food and water intake. Fasting blood glucose (FBG), insulin (FINS), serum creatinine (Scr), blood urea nitrogen (BUN), and urinary albumin excretion rate (UAER) were measured. HOMA-β and HOMA-IR assessed beta cell function and insulin resistance. Kidney pathology was evaluated by HE and Sirius Red staining. Kidney tissue levels of AGEs, oxidative stress markers (ROS, MDA, GSH, SOD), and RAGE expression (by WB) were analyzed. Molecular docking assessed binding between active compounds and core targets. Results: Network pharmacology identified 13 core targets, 8 enriched in the AGE-RAGE pathway. YQYTLF significantly reduced FBG, FINS, Scr, BUN, UAER, HOMA-IR, renal index, and pruritus while improving HOMA-β in DN rats. Renal pathological changes including Bowman's capsule dilation, mesangial proliferation, and fibrosis were alleviated. YQYTLF inhibited kidney AGEs, oxidative stress, and RAGE expression. Molecular docking confirmed strong binding between active ingredients and core targets. Conclusion: YQYTLF alleviates DN in rats by inhibiting AGE-RAGE pathway activation and reducing oxidative stress, providing a theoretical basis for DN therapy.
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For comparisons between two groups, a t-test was employed. Tukey’s post hoc test was used after a one-way or two-way ANOVA for comparisons between three or more groups. Statistical significance was defined as a p-value of less than 0.05.
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sections[16] "Statistical Analysis" paragraph 2
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For comparisons between two groups, a t-test was employed. Tukey’s post hoc test was used after a one-way or two-way ANOVA for comparisons between three or more groups. Statistical significance was defined as a p-value of less than 0.05.
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sections[4] "Collection and Analysis of DN Target Genes" paragraph 2
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We intersected the differentially expressed genes (DEGs) between DN kidney tissues and normal tissues (P < 0.05) from the GEO dataset GSE104948 with the drug targets.
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Thirteen core targets were confirmed, and eight of these targets were specifically enriched in the AGE-RAGE signaling pathway.
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sections[20] "Identification of Core Targets in YQYTLF Treatment for DN" paragraph 2
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After eliminating duplicates, 13 core targets were confirmed.
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Notably, these core targets were enriched in the top 10 KEGG pathways.
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sections[20] "Identification of Core Targets in YQYTLF Treatment for DN" paragraph 2
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Among them, 8 core targets (JUN, STAT3, IL6, TNF, CASP3, AKT1, BCL2, TP53) were specifically enriched in the AGE-RAGE signaling pathway
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re targets. Conclusion: YQYTLF alleviates DN in rats by inhibiting AGE-RAGE pathway activation an
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in STRING and visualized in Cytoscape. A DN rat model was treated with YQYTLF, with weekly m
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x, and pruritus while improving HOMA-β in DN rats. Renal pathological changes including Bowman
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targets. Conclusion: YQYTLF alleviates DN in rats by inhibiting AGE-RAGE pathway activation an
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40606302", "kind": "science-record", "revision": 4, "content_hash": "sha256:61a0e8d130150a22e3b6e88f5b86a011f8c7c509bfe674df0691853134d79849", "created_at": "2026-11-01T20:30:42Z", "updated_at": "2026-11-01T22:56:45Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Yiqi Yangyin Tongluo Recipe Alleviates Diabetic Kidney Disease Through AGE-RAGE Signalling Axis.", "doi": "10.2147/DMSO.S523784", "pmid": "40606302", "authors": ["Rucui Yu", "Ruiying Wu", "Tingting Chen", "Yan Zhang", "Xiangqing Chen"], "journal": "Diabetes, metabolic syndrome and obesity : targets and therapy", "year": 2025, "abstract": "Purpose: This study used network pharmacology to explore how Yiqi Yangyin Tongluo Formula (YQYTLF) alleviates diabetic nephropathy (DN), focusing on the AGE-RAGE signaling pathway.\nMethods: Active compounds and targets of YQYTLF were identified via TCMSP, and a herb-compound-target network was constructed using Cytoscape. Differentially expressed genes from DN kidney tissues (GEO dataset GSE104948) were intersected with drug targets for KEGG and GO enrichment analysis. Protein-protein interaction (PPI) networks were analyzed in STRING and visualized in Cytoscape. A DN rat model was treated with YQYTLF, with weekly monitoring of body weight, food and water intake. Fasting blood glucose (FBG), insulin (FINS), serum creatinine (Scr), blood urea nitrogen (BUN), and urinary albumin excretion rate (UAER) were measured. HOMA-β and HOMA-IR assessed beta cell function and insulin resistance. Kidney pathology was evaluated by HE and Sirius Red staining. Kidney tissue levels of AGEs, oxidative stress markers (ROS, MDA, GSH, SOD), and RAGE expression (by WB) were analyzed. Molecular docking assessed binding between active compounds and core targets.\nResults: Network pharmacology identified 13 core targets, 8 enriched in the AGE-RAGE pathway. YQYTLF significantly reduced FBG, FINS, Scr, BUN, UAER, HOMA-IR, renal index, and pruritus while improving HOMA-β in DN rats. Renal pathological changes including Bowman's capsule dilation, mesangial proliferation, and fibrosis were alleviated. YQYTLF inhibited kidney AGEs, oxidative stress, and RAGE expression. Molecular docking confirmed strong binding between active ingredients and core targets.\nConclusion: YQYTLF alleviates DN in rats by inhibiting AGE-RAGE pathway activation and reducing oxidative stress, providing a theoretical basis for DN therapy.", "claims": [{"id": "claim-method", "statement": "For comparisons between two groups, a t-test was employed. Tukey’s post hoc test was used after a one-way or two-way ANOVA for comparisons between three or more groups. Statistical significance was defined as a p-value of less than 0.05.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40606302", "locator": "sections[16] \"Statistical Analysis\" paragraph 2", "quote": "For comparisons between two groups, a t-test was employed. Tukey’s post hoc test was used after a one-way or two-way ANOVA for comparisons between three or more groups. Statistical significance was defined as a p-value of less than 0.05."}], "state": "complete"}, {"id": "claim-data-access", "statement": "We intersected the differentially expressed genes (DEGs) between DN kidney tissues and normal tissues (P < 0.05) from the GEO dataset GSE104948 with the drug targets.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40606302", "locator": "sections[4] \"Collection and Analysis of DN Target Genes\" paragraph 2", "quote": "We intersected the differentially expressed genes (DEGs) between DN kidney tissues and normal tissues (P < 0.05) from the GEO dataset GSE104948 with the drug targets."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Thirteen core targets were confirmed, and eight of these targets were specifically enriched in the AGE-RAGE signaling pathway.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40606302", "locator": "sections[20] \"Identification of Core Targets in YQYTLF Treatment for DN\" paragraph 2", "quote": "After eliminating duplicates, 13 core targets were confirmed."}, {"asset": "source:pmid:40606302", "locator": "sections[20] \"Identification of Core Targets in YQYTLF Treatment for DN\" paragraph 2", "quote": "Notably, these core targets were enriched in the top 10 KEGG pathways."}, {"asset": "source:pmid:40606302", "locator": "sections[20] \"Identification of Core Targets in YQYTLF Treatment for DN\" paragraph 2", "quote": "Among them, 8 core targets (JUN, STAT3, IL6, TNF, CASP3, AKT1, BCL2, TP53) were specifically enriched in the AGE-RAGE signaling pathway"}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Thirteen core targets were confirmed, and eight of these targets were specifically enriched in the AGE-RAGE signaling pathway.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:40606302"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE104948"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE104948"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40606302", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.2147/DMSO.S523784", "sha256": "sha256:3b3d888059ad080150657f95e14683b662df50a07270918ff451afc5dee585f4", "bytes": 49135, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.2147/DMSO.S523784", "version": null, "note": "Full article fetched from PMC; 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