Pharmacological Action

-Anti-aging activity

Fisetin exhibits a wide range of pharmacological activities, with particularly notable effects in the field of anti-aging. Studies have shown that fisetin can scavenge reactive oxygen species (ROS) in the body, reduce oxidative stress, regulate inflammatory responses, and selectively eliminate senescent cells. By doing so, it helps delay age-related tissue damage and functional decline, making it a promising natural molecule for anti-aging therapy.

Figure 1 Oral treatment with fisetin attenuates differences in frailty index score and grip strength with aging in old mice.

 (A) Frailty index score. (B) Normalized grip strength.

-Antioxidant activity

As a natural herbal compound, fisetin possesses strong antioxidant properties. Studies have shown that fisetin effectively scavenges reactive oxygen species (ROS), reduces oxidative stress-induced cellular damage, and enhances the activity of antioxidant enzymes, thereby boosting the body’s overall antioxidant capacity.

Figure 2 Effects of fisetin on oxidative and antioxidative parameters in an aging laying hen ovary model.

-Anti-inflammatory activity

Fisetin not only possesses multiple bioactivities such as antioxidant and anti-aging effects, but its anti-inflammatory action is also one of its most important and well-studied pharmacological properties. Studies have shown that fisetin can effectively inhibit the release of various inflammatory mediators, significantly reduce the secretion and gene expression of inflammation-related cytokines, thereby alleviating chronic inflammation and enhancing immune system function.

Figure 3 Fisetin treatment significantly alleviated lipopolysaccharide (LPS)-induced inflammatory responses in mice. 

(A) Myeloperoxidase (MPO) activity. (B) Expression level of TNF-α. (C) Expression level of IL-1β.

-Cardiovascular Protective Effects

Fisetin can improve endothelial function and reduce atherosclerosis-related markers, thereby preserving vascular elasticity and enhancing myocardial function. Additionally, it helps regulate blood lipid levels, lower cholesterol, and improve blood circulation, playing a positive role in maintaining the health of the cardiovascular system. Studies have shown that fisetin treatment can significantly alleviate DOX-induced cardiac fibrosis and myocardial hypertrophy.

Figure 4 Effects of fisetin treatment on DOX-induced cardiac tissue injury in rats.

 (A) Quantitative analysis of fibrosis area in Masson-stained sections. (B) Quantitative analysis of cardiomyocyte hypertrophy in WGA-stained sections.

-Antitumor activity

In numerous studies, fisetin has demonstrated strong antitumor activity. It can effectively inhibit the proliferation of tumor cells, induce apoptosis, and trigger autophagic processes, thereby disrupting cancer cell survival. In addition, fisetin exerts its anticancer effects by reducing intracellular reactive oxygen species (ROS) levels, modulating key signaling pathways involved in cell cycle arrest, and inhibiting angiogenesis required for tumor growth and metastasis.

Figure 5 Cytotoxic effects of fisetin on breast cancer cells.

Figure 6 Fisetin significantly inhibited the proliferation of human pancreatic cancer cells Patu-8988 in a dose-dependent manner. (A) Effects of different concentrations of fisetin on colony formation of Patu-8988 cells. (B) Effects of different concentrations of fisetin on the viability of HPNE, PANC-1, and Patu-8988 cells.

-Neuroprotective activity

Fisetin also exhibits notable neuroprotective effects. Studies have shown that it can effectively reduce neuroinflammation and oxidative stress, protecting neurons from damage. Additionally, fisetin activates key signaling pathways such as SIRT1 and Nrf2, eliminates excess free radicals, and inhibits the release of inflammatory cytokines, thereby helping to delay the onset and progression of neurodegenerative diseases such as Alzheimer's and Parkinson's disease. 

Figure 7 Effects of fisetin on HG-induced oxidative damage in HT22 neuronal cells. (A) Superoxide dismutase (SOD) activity. (B) Malondialdehyde (MDA) content.

-Anti-diabetic

Fisetin also exhibits significant antidiabetic activity by improving glucose metabolism disorders through multiple mechanisms. Studies have shown that fisetin can enhance insulin sensitivity, promote glucose utilization and metabolism, effectively inhibit diabetes-related oxidative stress and inflammatory responses, and protect pancreatic β-cell function. In addition, fisetin demonstrates positive effects in regulating lipid metabolism and improving insulin signaling pathways.

Figure 8 Fisetin inhibits α-glucosidase activity, thereby slowing glucose absorption. 

(A) Inhibitory activity of fisetin against α-glucosidase. (B) Inhibitory activity of acarbose against α-glucosidase.

-Antibacterial activities

Fisetin also exhibits notable antibacterial activity. Studies have shown that fisetin can disrupt the structure of bacterial cell walls and inhibit the proliferation of pathogenic bacteria, including common pathogens such as Staphylococcus aureus and Escherichia coli.

Figure 9 Fisetin inhibits the invasion of Salmonella Typhimurium into HeLa cells. (A) Invasion rate of Salmonella Typhimurium into host cells under different concentrations of fisetin. (B) In vitro growth curves of Salmonella Typhimurium under different concentrations of fisetin.

-Other activities

In addition, fisetin exhibits various other important biological activities, including liver protection, inhibition of fat accumulation thereby exerting anti-obesity effects, and promoting bone health as well as preventing and improving osteoporosis. At the neurological level, fisetin not only helps alleviate neurobehavioral disorders such as depression and anxiety but may also improve cognitive function through anti-inflammatory, antioxidant, and neurotransmitter-regulating mechanisms.

[1] Murray K O, Mahoney S A, Ludwig K R, et al. Intermittent Supplementation With Fisetin Improves Physical Function and Decreases Cellular Senescence in Skeletal Muscle With Aging: A Comparison to Genetic Clearance of Senescent Cells and Synthetic Senolytic Approaches[J]. Aging Cell, 2025: e70114.

[2] Yang Z, Zhang J, Yuan Q, et al. Flavonoid Fisetin Alleviates Ovarian Aging of Laying Chickens by Enhancing Antioxidant Capacity and Glucose Metabolic Homeostasis[J]. Antioxidants, 2024, 13(12): 1432.

[3] Jiang K, Yang J, Xue G, et al. Fisetin ameliorates the inflammation and oxidative stress in lipopolysaccharide-induced endometritis[J]. Journal of inflammation research, 2021: 2963-2978.

[4] Li D, Liu X, Pi W, et al. Fisetin attenuates doxorubicin-induced cardiomyopathy in vivo and in vitro by inhibiting ferroptosis through SIRT1/Nrf2 signaling pathway activation[J]. Frontiers in pharmacology, 2022, 12: 808480.

[5] Xiao Y, Liu Y, Gao Z, et al. Fisetin inhibits the proliferation, migration and invasion of pancreatic cancer by targeting PI3K/AKT/mTOR signaling[J]. Aging (Albany NY), 2021, 13(22): 24753.

[6] Zhang S, Xue R, Geng Y, et al. Fisetin prevents HT22 cells from high glucose-induced neurotoxicity via PI3K/Akt/CREB signaling pathway[J]. Frontiers in Neuroscience, 2020, 14: 241.

[7] Shen B, Shangguan X, Yin Z, et al. Inhibitory effect of fisetin on α-glucosidase activity: kinetic and molecular docking studies[J]. Molecules, 2021, 26(17): 5306.

[8] Li S, Liu H, Shu J, et al. Fisetin inhibits Salmonella Typhimurium type III secretion system regulator HilD and reduces pathology in vivo[J]. Microbiology spectrum, 2024, 12(1): e02406-23.