Evidence map›Paper›PMID 41593181›Full record

ArticleScientific reports2026

Kaempferol inhibits osteoclast differentiation and bone resorption by targeting the TNF-α/NF-κB and SRC/PI3K/AKT signaling pathways.

Qiting Yu, Taiping Jiang, Yunpeng Zhao, Zhaoming Liu, Zhiyu Guan

Abstract read
In one paragraph

Article in Scientific reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Qiting YuGuizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, 550000, China.
Taiping JiangDepartment of Sports Medicine(DSM), First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, 550000, China.
Yunpeng ZhaoGuizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, 550000, China.
Zhaoming LiuGuizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, 550000, China. 771990248@qq.com.
Zhiyu GuanSpine Surgery Department, First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine,Guiyang, Guizhou, 550000, China. gzy66689@163.com.

Funding

National Natural Science Foundation 82360938
6 · The paper itself

Abstract

Kaempferol exerts an important regulatory effect on osteoporosis, while its mechanism has not been fully elucidated. This study aimed to investigate the molecular mechanism underlying the anti-osteoporotic effect of kaempferol. Potential targets of kaempferol (197 genes) were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and SwissTargetPrediction databases. Meanwhile, osteoporosis-related targets (986 non-redundant genes) were compiled from disease-specific databases. Protein-protein interaction (PPI) network analysis was performed to identify 37 core targets. Subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed 3,295 biological processes and 205 signaling pathways, respectively. Molecular docking results demonstrated that kaempferol has high binding affinities with AKT, NF-κB, PI3K, SRC, and TNF-α. For experimental validation, RAW 264.7 cells were used: cell viability was assessed via the Cell Counting Kit 8 (CCK8) assay; osteoclast differentiation and bone resorption were evaluated through tartrate-resistant acid phosphatase (TRAP) staining and toluidine blue staining, respectively; oxidative stress markers (reactive oxygen species (ROS), superoxide dismutase (SOD), and malondialdehyde (MDA) were measured by enzyme-linked immunosorbent assay (ELISA); and molecular mechanisms were analyzed using quantitative real-time polymerase chain reaction (RT-qPCR) and Western blotting to detect osteoclast-related molecules (RANK, CSF1R, c-Fos, CTSK, and MMP-9) and signaling pathway proteins.​ Kaempferol significantly increased the viability of RAW 264.7 cells (P < 0.05). TRAP and toluidine blue staining showed dose-dependent decreases in osteoclast number and resorption area (P < 0.05). Additionally, kaempferol concentration-dependently reduced ROS and MDA levels while increasing SOD activity. It also significantly downregulated the expression of osteoclastogenesis-related genes (RANK, CSF1R, c-Fos, CTSK, and MMP-9; P < 0.05) and inhibited the activation of the TNF-α/NF-κB and SRC/PI3K/AKT signaling pathways.​ The predictions from network pharmacology were validated experimentally, confirming that kaempferol exerts dual inhibitory effects on osteoclast differentiation and oxidative stress. The coordinated inhibition of RANK/M-CSF signaling and its downstream TNF-α/NF-κB and SRC/PI3K/AKT pathways underpins the anti-resorptive activity of kaempferol.​.

Indexed as

Bone ResorptionCell DifferentiationKaempferolsOsteoclastsSignal TransductionAnimalsCell SurvivalMiceMolecular Docking SimulationNF-kappa BPhosphatidylinositol 3-KinasesProtein Interaction MapsProto-Oncogene Proteins c-aktRAW 264.7 CellsReactive Oxygen Speciessrc-Family KinaseskaempferolKaempferolsNF-kappa BPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktReactive Oxygen Speciessrc-Family KinasesTumor Necrosis Factor-alphaBone resorption functionKaempferolNetwork pharmacologySRC/PI3K/AKT signaling pathwayTNF-α/NF-κB signaling pathway

Identifiers

PMID41593181
PMCPMC12905433

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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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.