Evidence map›Paper›PMID 39725889›Full record

ArticleMolecular medicine (Cambridge, Mass.)2024

Investigating the inflammatory mechanism of notoginsenoside R1 in Diabetic nephropathy via ITGB8 based on network pharmacology and experimental validation.

ChangYan Li, Chen Geng, JiangMing Wang, Luyao Shi, JingYuan Ma, Zhang Liang, WenXing Fan

Abstract read
In one paragraph

Article in Molecular medicine (Cambridge, Mass.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

ChangYan Li *Department of Nephrology, First Affiliated Hospital, Kunming Medical University, Kunming, Yunnan Province, China.
Chen Geng *Department of Nephrology, First Affiliated Hospital, Kunming Medical University, Kunming, Yunnan Province, China.
JiangMing WangDepartment of Nephrology, First Affiliated Hospital, Kunming Medical University, Kunming, Yunnan Province, China.
Luyao ShiDepartment of Nephrology, First Affiliated Hospital, Kunming Medical University, Kunming, Yunnan Province, China.
JingYuan MaDepartment of Nephrology, First Affiliated Hospital, Kunming Medical University, Kunming, Yunnan Province, China.
Zhang LiangDepartment of Science and Technology, Kunming Medical University, Kunming, Yunnan Province, China.
WenXing FanDepartment of Nephrology, First Affiliated Hospital, Kunming Medical University, Kunming, Yunnan Province, China. fanwx2020@163.com.

Funding

535 Talent Project of First Affiliated Hospital of Kunming Medical University 2022535D06National Natural Science Foundation of China 82160142Outstanding-Youth Cultivation Project for Union Foundation of Yunnan Applied Basic Research Projects 202201AY070001-044Reserve Talents Project for Young and Middle-aged Academic and Technical Leaders of Yunnan Province 202205AC160062Yunnan Provincial Education Department Scientific Research Fund Project 2024Y229
6 · The paper itself

Abstract

backgroundDiabetes often causes diabetic nephropathy (DN), a serious long-term complication. It is characterized by chronic proteinuria, hypertension, and kidney function decline, can progress to end-stage renal disease, lowering patients' quality of life and lifespan. Inflammation and apoptosis are key to DN development. Network pharmacology, clinical correlation, and basic experimental validation to find out how NGR1 might work to reduce inflammation in DN treatment. The study aims to improve DN treatment with new findings.

methodsTo determine how NGR1 treats DN, this study used network pharmacology, clinical correlation, and basic experimental validation. Three methods were used to predict NGR1 drug targets: ChEMBL, SuperPred, and Swiss Target Prediction. Drug targets are linked to diseases by molecular docking. A clinical correlation analysis using the Nephroseq Classic (V4) database looked at the strong link between medication targets and the development, progression, and renal function of DN. Additional research showed that NGR1 reduces high blood sugar-induced podocyte inflammation.

resultsThe integrin subunit beta 8 (ITGB8) protein is a potential NGR1 therapeutic target for DN. It may be linked to inflammatory proteins like caspase 3 and IL-18. Validation of the molecular docking showed that SER-407, ALA-22, Ala-343, and TYR-406 form hydrogen bonds with NGR1 and ITGB8. These interactions represent pharmacodynamic targets. Clinical correlation showed that DN patients had significantly lower ITGB8 expression levels than healthy individuals. Between 50 and 80 years old, DN patients' ITGB8 expression levels decreased. ITGB8 expression was lowest in renal function conditions, with eGFR values of 15-29 ml/min/1.73 m2. In the db/db mouse model, downregulation of ITGB8 expression in renal tissue was associated with renal inflammatory damage. The hyperglycemic group had significantly lower levels of nephrin and caspase-3 protein, but higher levels of cleaved caspase-1 protein. Giving NGR1 in different amounts (1, 3, 10, and 30 µM) greatly decreased the expression of caspase3, stopped the expression of cleaved caspase1, and lowered the damage caused by NLRP3 in podocytes.

conclusionWe identified several NGR1 pharmacological targets and found that the ITGB8 protein is a key drug target linked to inflammation and DN. ITGB8 is critical for DN development and can help to reduce high blood sugar-induced podocyte inflammation.

Indexed as

Diabetic NephropathiesMolecular Docking SimulationNetwork PharmacologyAnimalsDisease Models, AnimalFemaleGinsenosidesHumansInflammationMaleMiceMiddle AgedPodocytesGinsenosidesnotoginsenoside R1Diabetic nephropathyInflammatory injuryITGB8Network pharmacologyNGR1

Identifiers

PMID39725889
PMCPMC11674371

What Socratic holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.