What are the side effects of fisetin?

What is Fisetin?

Fisetin (3,3′,4′,7-tetrahydroxyflavone) is a phytochemical synthesized in various fruits and vegetables and belongs to flavonoids. Flavonoids are composed of a fifteen-carbon skeleton with two benzene rings connected by a pyrane ring [1].

Among various bioactivities of flavonoids, the best described is their anti-oxidant activity, which is dependent on the number and configuration of hydroxyl groups [2]. Like other flavonoids, fisetin shows anti-oxidant, anti-viral, anti-bacterial, and anti-inflammatory activities [1]. A recent study revealed that fisetin demonstrates an anti-diabetic effect through its α-glucosidase inhibitor activity [3]. Fisetin can significantly reduce age-related accumulation of lipid peroxidation and protein oxidation [4]. In rats, cellular ROS levels are decreased, while the expression of anti-oxidant enzymes CAT and SOD is increased by fisetin [4]. The anti-carcinogenic activity of fisetin has also been reported through in vitro and in vivo studies. The growth of human lung cancer cells is inhibited by treatment with fisetin [5]. Fisetin 98% can repress the proliferation and migration of human oral squamous cell carcinoma and inhibit tumor growth [6]. In aged tissues, fisetin can induce apoptosis specifically in senescent cells and reduce the level of cellular oxidative damage [7,8]. Fisetin was the most potent inhibitor for cellular senescence among ten flavonoids, including rutin, quercetin, myricetin, and so on [9]. Both of the flavonoids fisetin and kaempferol increased the resistance to oxidative stress, but only kaempferol reduced the accumulation of lipofuscin in C. elegans [10]. Dietary supplementation with fisetin in old mice can significantly increase both the mean and maximum lifespan [9]. Fisetin also shows beneficial effects on neurodegenerative diseases via its neuroprotective activity. Administration of fisetin can restore cognitive and memory impairments caused by D-galactose.

What is the function of Fisetin?

Fisetin is a naturally occurring flavonoid compound that has a variety of significant effects. The following is a detailed summary of the effects of fisetin:

√ Antioxidation and anti-aging

Fisetin 98% is a powerful antioxidant that neutralizes free radicals and slows down the aging process of cells.In the field of beauty, fisetin is widely used in anti-wrinkle products, which can stimulate the synthesis of skin collagen, increase skin elasticity, reduce the occurrence of wrinkles and fine lines, and make the skin firmer and smoother.

√ Neuroprotective effect

Fisetin has sleep regulating, anti-anxiety, and anti-depressant effects, can improve memory, and has a positive effect on improving neurodegenerative diseases such as Alzheimer's disease.

√ Anti-inflammatory effect

Fisetin has significant anti-inflammatory effects on inflammatory diseases such as arthritis and other osteoarthritis, pneumonia and pulmonary fibrosis, myocarditis, gout, and stroke.

√ Liver protection

Fisetin helps protect liver health, has an auxiliary therapeutic effect on liver diseases such as jaundice and hepatitis, and can remove senescent cells in the liver.

√ Regulate blood sugar and promote fat metabolism

Fisetin has the effect of regulating blood sugar and helps maintain the stability of blood sugar levels.At the same time, it can also promote fat metabolism, assist weight loss, and improve bone health.

√ Eye protection effect

Fisetin is the precursor of vitamin A, which plays an important role in maintaining eye health and promoting vision, especially in improving night vision and night blindness.

√ Enhance immunity

Fisetin can enhance the function of the immune system, improve the body's resistance, and prevent colds and other respiratory infections.

√ Other functions

Fisetin also has an astringent effect, which can shrink pores, reduce oil secretion, and improve the texture of oily and rough skin.It can also regulate the water and oil balance of the skin, keeping the skin fresh and soft.

In addition, fisetin also has a synergistic effect and can work synergistically with turmeric, berberine, citrulline, collagen and other substances to enhance the effect.

What are the side effects of fisetin?

As a naturally occurring flavonoid, fisetin has many significant effects, but excessive intake or improper use may also cause some side effects. The following is a detailed summary of the side effects of fisetin:

1.Skin reaction

Excessive intake of fisetin may cause yellowing of the skin. This is because during the metabolism and excretion of fisetin 98% in the body, it may affect the metabolism of skin pigments, resulting in changes in skin color.

2.Other adverse reactions

In addition to yellowing of the skin, excessive intake of fisetin may also cause other adverse reactions, such as nausea, vomiting, diarrhea and other digestive system symptoms. These symptoms may vary from person to person, but usually resolve gradually after you stop taking fisetin.

3.Precautions

Use in moderation: Due to the potential side effects of fisetin, professional advice should be followed when using it and intake should be strictly controlled. Avoid excessive intake that may cause adverse reactions.

Individual Differences: Different groups of people may have different tolerances to fisetin. Therefore, it is best to consult a doctor or nutritionist for advice before use to understand whether you are suitable for using fisetin and the appropriate intake amount.

Drug Interactions: Fisetin may interact with other drugs, affecting their efficacy or increasing the risk of adverse reactions. Therefore, when using fisetin, you should inform your doctor about other drugs you are taking to avoid drug-drug interactions.

Summary

Fisetin supplement has a variety of significant effects, including antioxidant and anti-aging, neuroprotection, anti-inflammatory effects, liver protection, regulating blood sugar and promoting fat metabolism, eye protection, and enhancing immunity. These effects make fisetin have broad application prospects in the fields of medicine, beauty, food and cosmetics. However, please note that when using fisetin-related products or supplements, you should follow professional advice and use in moderation.

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Reference:

1.Ravula A.R., Teegala S.B., Kalakotla S., Pasangulapati J.P., Perumal V., Boyina H.K. Fisetin, potential flavonoid with multifarious targets for treating neurological disorders: An updated review. Eur. J. Pharmacol. 2021;910:174492. doi: 10.1016/j.ejphar.2021.174492. 

2.Kumar S., Pandey A.K. Chemistry and Biological Activities of Flavonoids: An Overview. Sci. World J. 2013;2013:162750. doi: 10.1155/2013/162750. 

3.Andalia N., Salim M.N., Saidi N., Ridhwan M., Iqhrammullah M., Balqis U. Molecular docking reveals phytoconstituents of the methanol extract from Muntingia calabura as promising α-glucosidase jnhibitors. Karbala Int. J. Mod. Sci. 2022;8:4. doi: 10.33640/2405-609X.3236.

4.Singh S., Singh A.K., Garg G., Rizvi S.I. Fisetin as a caloric restriction mimetic protects rat brain against aging induced oxidative stress, apoptosis and neurodegeneration. Life Sci. 2018;193:171–179. doi: 10.1016/j.lfs.2017.11.004. 

5.Khan N., Afaq F., Khusro F.H., Mustafa Adhami V., Suh Y., Mukhtar H. Dual inhibition of phosphatidylinositol 3-kinase/Akt and mammalian target of rapamycin signaling in human nonsmall cell lung cancer cells by a dietary flavonoid fisetin. Int. J. Cancer. 2012;130:1695–1705. doi: 10.1002/ijc.26178. 

6.Li Y., Jia S., Dai W. Fisetin Modulates Human Oral Squamous Cell Carcinoma Proliferation by Blocking PAK4 Signaling Pathways. Drug Des. Dev. Ther. 2020;14:773–782. doi: 10.2147/DDDT.S229270. 

7.Martel J., Ojcius D.M., Wu C., Peng H., Voisin L., Perfettini J., Ko Y., Young J.D. Emerging use of senolytics and senomorphics against aging and chronic diseases. Med. Res. Rev. 2020;40:2114–2131. doi: 10.1002/med.21702. 

8.Zhu Y., Doornebal E.J., Pirtskhalava T., Giorgadze N., Wentworth M., Fuhrmann-Stroissnigg H., Niedernhofer L.J., Robbins P.D., Tchkonia T., Kirkland J.L. New agents that target senescent cells: The flavone, fisetin, and the BCL-XL inhibitors, A1331852 and A1155463. Aging. 2017;9:955–963. doi: 10.18632/aging.101202. 

9.Yousefzadeh M.J., Zhu Y., McGowan S.J., Angelini L., Fuhrmann-Stroissnigg H., Xu M., Ling Y.Y., Melos K.I., Pirtskhalava T., Inman C.L., et al. Fisetin is a senotherapeutic that extends health and lifespan. eBioMedicine. 2018;36:18–28. doi: 10.1016/j.ebiom.2018.09.015.34.Kampkötter A., Nkwonkam C.G., Zurawski R.F., Timpel C., Chovolou Y., Wätjen W., Kahl R. Effects of the flavonoids kaempferol and fisetin on thermotolerance, oxidative stress and FoxO transcription factor DAF-16 in the model organism Caenorhabditis elegans. Arch. Toxicol. 2007;81:849–858. doi: 10.1007/s00204-007-0215-4. 35.Ahmad S., Khan A., Ali W., Jo M.H., Park J., Ikram M., Kim M.O. Fisetin Rescues the Mice Brains Against D-Galactose-Induced Oxidative Stress, Neuroinflammation and Memory Impairment. Front. Pharmacol. 2021;12:612078. doi: 10.3389/fphar.2021.612078.