Protective Effects of Food-Derived Kaempferol on Pancreatic β-Cells in Type 1 Diabetes Mellitus

Abstract

Background: Kaempferol (KPF), a flavonoid abundant in edible plants, possesses potent anti-inflammatory and antioxidant properties beneficial with notable health benefits.

Objective: To evaluate the protective effects of KPF on metabolic disturbances and pancreatic damage in a Type 1 diabetes mellitus (T1DM) mouse model.

Methods: Male C57BL/6 mice were divided into normal, T1DM, T1DM + KPF 25 mg/kg, and T1DM + KPF 50 mg/kg groups. T1DM was induced by streptozotocin (STZ). KPF was administered via intraperitoneal injection for 2 weeks. After 4 weeks from the start, metabolic parameters, pancreatic histology, and plasma metabolites were analyzed. Network pharmacology and molecular docking identified key targets and pathways. In vitro, INS-1 cells were used to assess reactive oxygen species (ROS) production and apoptosis.

Results: KPF significantly reduced blood glucose (GLU) and triglyceride (TG) levels, increased high-density lipoprotein (HDL) levels, and preserved pancreatic β-cell structure. Metabolomics revealed changes in energy metabolism and oxidative stress-related metabolites. Network analysis highlighted the PI3K/AKT/mTOR pathway, with strong binding affinities to targets such as AKT1. In vitro, KPF decreased ROS production in INS-1 cells; this effect was reversed by a PI3K/AKT inhibitor. KPF also reduced apoptosis in INS-1 cells.

Conclusions: KPF ameliorates metabolic disturbances and pancreatic damage in T1DM mice, suggesting potential as a functional food ingredient for diabetes management.

Keywords: kaempferol; metabolic disturbances; metabolomics; pancreatic β-cell protection; type 1 diabetes.

Figure 1

Effects of KPF on metabolic parameters and pancreatic morphology in T1DM Mice. (A) water intake, (B) food intake, (C) liver index, (D) blood glucose levels (GLU), (E) triglyceride (TG) levels, (F) high-density lipoprotein (HDL) levels, and (G) representative hematoxylin and eosin (H&E) staining of pancreatic tissue. The relative islet area was quantified, highlighted using arrows in the image, and is presented as a bar chart. Data represent a single measurement and therefore do not include statistical analysis. (H) Homeostasis Model Assessment of Beta-cell Function (HOMA-β). Data are presented as mean ± SD. * p < 0.05, ** p < 0.01 compared to the T1DM group.

Figure 2

Metabolic profiling and biomarker analysis of T1DM and KPF-treated Mice. (A) Principal component analysis (PCA) score plots for normal, T1DM, and T1DM + KPF50 groups in positive and negative ion modes. (B) PCA score plots comparing T1DM and T1DM + KPF50 groups. (C) Volcano plot showing significantly altered metabolites between T1DM and T1DM + KPF50 groups, with 94 endogenous metabolites identified. Statistical thresholds were set at fold change (FC) > 2 and p < 0.05. Blue dots represent significantly downregulated metabolites, and green dots represent significantly upregulated metabolites.

Figure 3

Network pharmacology analysis of KPF in T1DM Mice. (A) Venn diagram showing the overlap between KPF drug targets and T1DM-related gene targets. (B) Compound-target-pathway network based on KEGG enrichment analysis. (C) Visualization of 14 core targets identified by PPI network analysis. (D) Metabolite-gene interaction network showing four key targets: PTGS2, AKT1, SRC, and MPO. (E) Molecular docking of KPF with these four key targets. (F) Binding affinity results of KPF with key targets (kcal/mol).

Figure 4

Effect of KPF on caspase-9 expression and AKT-mediated ROS levels in INS-1 cells. (A) Immunofluorescence staining of caspase-9 in INS-1 cells after STZ stimulation and KPF treatment. (B) ROS levels in INS-1 cells after treatment with KPF and PI3K-AKT pathway inhibitor LY294002. Data are presented as mean ± SD. * p < 0.05, ** p < 0.01 compared to the model group; ns indicates non-significance.