Kaempferol Protects Against High Glucose-Induced Cell Damage, Suggests Study
China: Researchers have found in a new study that kaempferol reduces oxidative stress and apoptosis caused by high glucose (HG), with its protective effects linked to Sirt3 expression and activation of the ROS-sensitive Akt/FoxO3a signaling pathway. These findings highlight the potential of this dietary flavonoid as a therapeutic candidate for diabetic nephropathy, a major complication of diabetes marked by kidney damage.
The study, published in BMC Nephrology, was led by Xiao-Cui Jiao and colleagues from the Department of Nephrology at Capital Medical University Electric Teaching Hospital, Beijing. Their work focused on renal tubular epithelial cells, which are particularly vulnerable to the harmful effects of prolonged high blood glucose levels. Oxidative stress and programmed cell death (apoptosis) in these cells are key drivers in the progression of diabetic nephropathy, and targeting these processes could help prevent or slow kidney damage.
Kaempferol (KMP), a naturally occurring flavonoid found in many fruits and vegetables, is already known for its antioxidant, anti-inflammatory, and anti-apoptotic properties. To test its protective capacity in a diabetic context, the research team cultured human renal tubular epithelial (HK-2) cells under high-glucose conditions and treated them with different concentrations of kaempferol. Cell viability was assessed with the MTS assay to determine a safe and effective dose.
The study led to the following notable findings:
- HK-2 cells exposed to high glucose and treated with 10 µM kaempferol showed significantly higher viability than cells exposed to high glucose alone.
- Kaempferol reversed high-glucose–induced reductions in the antioxidant enzymes superoxide dismutase 2 (SOD2) and catalase.
- Treatment lowered levels of reactive oxygen species (ROS).
- Markers of apoptosis, including the Bax/Bcl-2 ratio and cleaved caspase-3, were decreased.
- Western blot and real-time PCR showed increased Sirt3 expression and higher phosphorylation ratios of Akt and FoxO3a, indicating activation of the ROS-sensitive Akt/FoxO3a pathway.
- Downregulation of Sirt3 weakened kaempferol’s protective effects, leading to reduced cell viability and increased ROS levels.
- Findings indicate Sirt3 is a key mediator of kaempferol’s antioxidant and anti-apoptotic actions.
The authors noted that their findings demonstrate for the first time that kaempferol exerts renal protective effects by enhancing Sirt3 expression and modulating the ROS-sensitive Akt/FoxO3a pathway. Although the study was conducted in cell cultures, the results point to kaempferol’s potential as a natural therapeutic agent for diabetic nephropathy.
"Further studies in animal models and clinical settings will be needed to confirm these effects and establish appropriate dosing strategies. Nevertheless, the research provides a strong rationale for exploring kaempferol-rich diets or supplements as part of future interventions aimed at preventing or mitigating kidney damage in patients with diabetes," the authors concluded.
Reference:
Jiao, XC., Li, Y., Wu, D. et al. The protective effect of kaempferol on high glucose-stimulated renal tubular epithelial cells. BMC Nephrol 26, 477 (2025). https://doi.org/10.1186/s12882-025-04404-9
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