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Fisetin: A natural senotherapeutic with potent antioxidant properties against aging

Article
June 25, 2022
By
Ehab Naim, MBA.

Fisetin, a bioactive compound found in edible plants, is reported to have a number of biological activities, including antioxidant, antimicrobial, anticancer, antidiabetic, and other properties

Compound description

Fisetin is a bioactive compound found in edible plants, like strawberries, blueberries, apples, grapes, cucumber, onion, and others (1). According to research, fisetin is reported to have a number of biological activities, including antioxidant, antimicrobial, anticancer, antidiabetic, and other properties (1-3). 

Properties 

Oxidative stress, which results from the presence of excessive reactive oxygen species (ROS), has been implicated in speeding up the aging process by damaging the DNA, among other mechanisms (4). ROS are usually produced from bodily functions, like metabolism and energy production. Under normal conditions, ROS are eliminated by antioxidants, like glutathione, inside the body (3, 4). However, diseases develop when ROS production exceeds elimination capacity, where excess ROS has been linked to many age-related conditions like cancer, diabetes or neurodegeneration (4, 5). Fisetin is a strong antioxidant.

Use as a supplement

Through its activity as an antioxidant, fisetin has been found to be an efficient eliminator of ROS (1). Research revealed that, when compared to Trolox (a type of vitamin E with strong antioxidant potency) and butylated hydroxyanisole (an antioxidant), fisetin was more effective (1, 3). This means that fisetin actively scavenges ROS and protects the DNA even at low concentrations. Further research revealed that fisetin increases antioxidant biomarkers, like plasma catalase, glutathione peroxidase, and reductase enzymes (1).

The value of fisetin has also been investigated in cellular senescence (a permanent cell cycle arrest in which cells resist apoptosis. It is considered a protective mechanism against cancer and a hallmark of aging) (6). Senescent cells have been found to increase the expression of pro-inflammatory proteins, which negatively affect the body and result in accelerated aging (7). In addition, research has highlighted that small amounts of these cells in tissues are enough to disrupt the function. Preclinical studies on murine and cellular models revealed that fisetin supplementation resulted in increased healthspan and lifespan, highlighting the value of this compound as a senotherapeutic (7, 8).

Moreover, fisetin has been found to have a neuroprotective role. The research highlighted that it preserves cognitive function and reduces deficits in mice prone to accelerated aging (9). In the study, the bioactive compound was found to reduce inflammatory biomarkers, improve synaptic function, and decrease stress. This highlights the benefits of fisetin on cognitive functions.

According to studies, humans consume about 0.4 mg/day of fisetin from various fruits and vegetables (6, 7). The literature reported the use of doses ranging from 200 mg/day to 800 mg/day in humans (10).

In our Marketplace under the vendor DoNotAge, you can find fisetin as capsules (Pure Fisetin). Pure Fisetin provides the body with 800mg of the bioactive molecule per serving (serving is two capsules). This dose is sufficient to help the body control senescent cells, decelerate the aging process, fight many age-related conditions, and much more.

Side effects

There were no reports of adverse events with the use of fisetin, even at high doses. However, it is important to note that there are insufficient studies on humans to determine the safety profile of fisetin (7). Therefore, it is best to use this supplement after consulting a licensed healthcare professional, like a physician or pharmacist.

 

References

1.            Antika L, Dewi R. Pharmacological aspects of fisetin. Asian Pacific Journal of Tropical Biomedicine. 2021;11(1):1-9.

2.            Sundarraj K, Raghunath A, Perumal E. A review on the chemotherapeutic potential of fisetin: In vitro evidences. Biomedicine & Pharmacotherapy. 2018;97:928-40.

3.            Khan N, Syed DN, Ahmad N, Mukhtar H. Fisetin: A Dietary Antioxidant for Health Promotion. Antioxidants & Redox Signaling. 2012;19(2):151-62.

4.            Liguori I, Russo G, Curcio F, Bulli G, Aran L, Della-Morte D, et al. Oxidative stress, aging, and diseases. Clin Interv Aging. 2018;13:757-72.

5.            Ray PD, Huang B-W, Tsuji Y. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cellular signalling. 2012;24(5):981-90.

6.            Grynkiewicz G, Demchuk OM. New Perspectives for Fisetin. Frontiers in Chemistry. 2019;7.

7.            Yousefzadeh MJ, Zhu Y, McGowan SJ, Angelini L, Fuhrmann-Stroissnigg H, Xu M, et al. Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine. 2018;36:18-28.

8.            Elsallabi O, Patruno A, Pesce M, Cataldi A, Carradori S, Gallorini M. Fisetin as a Senotherapeutic Agent: Biopharmaceutical Properties and Crosstalk between Cell Senescence and Neuroprotection. Molecules. 2022;27(3):738.

9.            Currais A, Farrokhi C, Dargusch R, Armando A, Quehenberger O, Schubert D, et al. Fisetin Reduces the Impact of Aging on Behavior and Physiology in the Rapidly Aging SAMP8 Mouse. The Journals of Gerontology: Series A. 2018;73(3):299-307.

10.          Hodgin KS, Donovan EK, Kekes-Szabo S, Lin JC, Feick J, Massey RL, et al. A placebo-controlled, pseudo-randomized, crossover trial of botanical agents for gulf war illness: resveratrol (Polygonum cuspidatum), Luteolin, and Fisetin (Rhus succedanea). International Journal of Environmental Research and Public Health. 2021;18(5):2483.

 

Compound description

Fisetin is a bioactive compound found in edible plants, like strawberries, blueberries, apples, grapes, cucumber, onion, and others (1). According to research, fisetin is reported to have a number of biological activities, including antioxidant, antimicrobial, anticancer, antidiabetic, and other properties (1-3). 

Properties 

Oxidative stress, which results from the presence of excessive reactive oxygen species (ROS), has been implicated in speeding up the aging process by damaging the DNA, among other mechanisms (4). ROS are usually produced from bodily functions, like metabolism and energy production. Under normal conditions, ROS are eliminated by antioxidants, like glutathione, inside the body (3, 4). However, diseases develop when ROS production exceeds elimination capacity, where excess ROS has been linked to many age-related conditions like cancer, diabetes or neurodegeneration (4, 5). Fisetin is a strong antioxidant.

Use as a supplement

Through its activity as an antioxidant, fisetin has been found to be an efficient eliminator of ROS (1). Research revealed that, when compared to Trolox (a type of vitamin E with strong antioxidant potency) and butylated hydroxyanisole (an antioxidant), fisetin was more effective (1, 3). This means that fisetin actively scavenges ROS and protects the DNA even at low concentrations. Further research revealed that fisetin increases antioxidant biomarkers, like plasma catalase, glutathione peroxidase, and reductase enzymes (1).

The value of fisetin has also been investigated in cellular senescence (a permanent cell cycle arrest in which cells resist apoptosis. It is considered a protective mechanism against cancer and a hallmark of aging) (6). Senescent cells have been found to increase the expression of pro-inflammatory proteins, which negatively affect the body and result in accelerated aging (7). In addition, research has highlighted that small amounts of these cells in tissues are enough to disrupt the function. Preclinical studies on murine and cellular models revealed that fisetin supplementation resulted in increased healthspan and lifespan, highlighting the value of this compound as a senotherapeutic (7, 8).

Moreover, fisetin has been found to have a neuroprotective role. The research highlighted that it preserves cognitive function and reduces deficits in mice prone to accelerated aging (9). In the study, the bioactive compound was found to reduce inflammatory biomarkers, improve synaptic function, and decrease stress. This highlights the benefits of fisetin on cognitive functions.

According to studies, humans consume about 0.4 mg/day of fisetin from various fruits and vegetables (6, 7). The literature reported the use of doses ranging from 200 mg/day to 800 mg/day in humans (10).

In our Marketplace under the vendor DoNotAge, you can find fisetin as capsules (Pure Fisetin). Pure Fisetin provides the body with 800mg of the bioactive molecule per serving (serving is two capsules). This dose is sufficient to help the body control senescent cells, decelerate the aging process, fight many age-related conditions, and much more.

Side effects

There were no reports of adverse events with the use of fisetin, even at high doses. However, it is important to note that there are insufficient studies on humans to determine the safety profile of fisetin (7). Therefore, it is best to use this supplement after consulting a licensed healthcare professional, like a physician or pharmacist.

 

References

1.            Antika L, Dewi R. Pharmacological aspects of fisetin. Asian Pacific Journal of Tropical Biomedicine. 2021;11(1):1-9.

2.            Sundarraj K, Raghunath A, Perumal E. A review on the chemotherapeutic potential of fisetin: In vitro evidences. Biomedicine & Pharmacotherapy. 2018;97:928-40.

3.            Khan N, Syed DN, Ahmad N, Mukhtar H. Fisetin: A Dietary Antioxidant for Health Promotion. Antioxidants & Redox Signaling. 2012;19(2):151-62.

4.            Liguori I, Russo G, Curcio F, Bulli G, Aran L, Della-Morte D, et al. Oxidative stress, aging, and diseases. Clin Interv Aging. 2018;13:757-72.

5.            Ray PD, Huang B-W, Tsuji Y. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cellular signalling. 2012;24(5):981-90.

6.            Grynkiewicz G, Demchuk OM. New Perspectives for Fisetin. Frontiers in Chemistry. 2019;7.

7.            Yousefzadeh MJ, Zhu Y, McGowan SJ, Angelini L, Fuhrmann-Stroissnigg H, Xu M, et al. Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine. 2018;36:18-28.

8.            Elsallabi O, Patruno A, Pesce M, Cataldi A, Carradori S, Gallorini M. Fisetin as a Senotherapeutic Agent: Biopharmaceutical Properties and Crosstalk between Cell Senescence and Neuroprotection. Molecules. 2022;27(3):738.

9.            Currais A, Farrokhi C, Dargusch R, Armando A, Quehenberger O, Schubert D, et al. Fisetin Reduces the Impact of Aging on Behavior and Physiology in the Rapidly Aging SAMP8 Mouse. The Journals of Gerontology: Series A. 2018;73(3):299-307.

10.          Hodgin KS, Donovan EK, Kekes-Szabo S, Lin JC, Feick J, Massey RL, et al. A placebo-controlled, pseudo-randomized, crossover trial of botanical agents for gulf war illness: resveratrol (Polygonum cuspidatum), Luteolin, and Fisetin (Rhus succedanea). International Journal of Environmental Research and Public Health. 2021;18(5):2483.

 

Article reviewed by
Dr. Ana Baroni MD. Ph.D.
SCIENTIFIC & MEDICAL ADVISOR
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Dr. Ana Baroni MD. Ph.D.

Scientific & Medical Advisor
Quality Garant

Ana has over 20 years of consultancy experience in longevity, regenerative and precision medicine. She has a multifaceted understanding of genomics, molecular biology, clinical biochemistry, nutrition, aging markers, hormones and physical training. This background allows her to bridge the gap between longevity basic sciences and evidence-based real interventions, putting them into the clinic, to enhance the healthy aging of people. She is co-founder of Origen.life, and Longevityzone. Board member at Breath of Health, BioOx and American Board of Clinical Nutrition. She is Director of International Medical Education of the American College of Integrative Medicine, Professor in IL3 Master of Longevity at Barcelona University and Professor of Nutrigenomics in Nutrition Grade in UNIR University.

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