Flavonol Fisetin – Vital substance with a senolytic effect
Flavonol Fisetin is found in numerous plants. It is offered as a vital substance in food supplements. Numerous studies prove its positive effects on brain performance, its senolytic effect and give it significance for pharmacology and, due to its antioxidant and anti-aging effectiveness, also for cosmetics.
Flavonol Fisetin was first extracted from the Venetian sumac in 1833.
The name is derived from the plant, which is also known as wig tree or fiset wood. Another name, cotinine, comes from the botanical name Cotinus coggygria or Rhus cotinus.
Flavonol Fisetin has also been isolated from other plants, such as mulberry leaves or strawberries, using methanol.
In the following years, the chemical properties of the flavonol were further deciphered and it was finally synthesised in 1904.
Description and occurrence
Flavonol Fisetin is one of the flavonols, just like kaempferol, quercetin and myricetin.
Flavonols are flavonoids with a ketone group. They are building blocks of proanthocyanidins and are found in numerous fruits and vegetables.
The highest concentrations are found in strawberries (≈ 160 µg/g) and apples (≈ 27 µg/g), but this plant pigment is also found in kiwis, persimmons, cucumbers, onions and capers.
With a diet rich in vegetables and fruit, we take in an average of 0.4 g of Flavonol Fisetin daily.
Effects
Flavonol Fisetin has numerous health and longevity-supporting effects and is known for its antioxidant and nitrosative, antimicrobial, anti-inflammatory, anti-diabetic properties and mitochondrial-protective effects. Its senolytic properties are increasingly being researched and make it an interesting agent for the prevention of neurodegenerative diseases such as Alzheimer’s, Parkinson’s and Huntington’s. Reactive oxygen species (ROS) and nitrogen species (RNS) attack neurons, cause lipid peroxidation, increase protein glycolisation and inflammatory reactions, which also destroy skin structures.
Pharmacological effect
Cell cultures and animal experiments have demonstrated the senolytic and anti-neoplastic effect of Finestin. Studies show that Flavonol Fisetin promotes long-term memory.
The senolytic effect of Flavonol Fisetin in cell cultures has already been reported several times. The substance was used in concentrations of 1-50µg/ml.
A senolytic effect of Flavonol Fisetin has been demonstrated both in cell cultures and in mice.
In the mice studied, oral administration of Flavonol Fisetin led to a delay in the onset of symptoms of the disease and to an extended lifespan.
Essential to these effects is the reduction of age-induced signalling pathways and the promotion of apoptosis.
These effects are explained by the activation of sirtuin, a life-prolonging and stress-defending protein, the blocking of the P13K-Akt signalling pathway, the inhibition of topoisomerase and other anti-apoptotic factors, e.g. proteins of the Bcl-2 group.
Flavonol Fisetin can even cause pancreatic cancer cells to stop dividing in the G1 phase of the cell cycle.
Food supplements
Its many bioactive, cytoprotective and senolytic properties make Flavonol Fisetin a vital substance that is used in food supplements as a health-promoting and neuroprotective phytamine.
Dosages of 100 to 500 mg/day are used here.
Senolytics and zombie cells
In contrast to young, active cells, zombie cells have lost their ability to divide and no longer renew tissue. They promote aging processes and health problems. With increasing age, these senescent cells accumulate in the body and also contribute to skin aging. Healthy cells only divide until the telomeres have shortened to a critical length. The cell then stops dividing to avoid DNA damage. It becomes senescent but remains metabolically active. These zombie cells secrete substances such as cytokines and proteases, which promote inflammatory processes in the body and thus exacerbate the signs of aging. By remaining in the cell structure, they increase the risk of age-related diseases such as dementia, diabetes and cancer.
In younger years, zombie cells can play a role in wound healing through their pro-inflammatory effect, but they become problematic with age.
Due to the declining performance of the immune system, senescent cells are no longer completely removed and release cell-damaging and pro-inflammatory substances. This phenomenon is known as the senescence-associated secretory phenotype (SASP).
Oxidative stress and nitro-stress also cause senescent cells, which accelerate degenerative processes in all tissues, including the skin. The consequences are impaired wound healing, reduced elasticity, wrinkles, pigment spots, hair loss and thinning hair.
Senescent cells damage the surrounding tissue, causing it to age as well, and thus form networks through which they escape cell death.
This is where senolytics come into play
The key term around which the effects of Flavonol Fisetin revolve is senolytics.
These substances have a pro-apoptotic effect on senescent cells (zombie cells), i.e. they kill them or initiate their dissolution (senolysis). Apoptosis, i.e. cell death, is usually achieved by inhibiting anti-apoptotic enzymes and the corresponding signalling pathways.
Quercetin and Flavonol Fisetin , among others, have been identified as senolytics with anti-ageing effects. These molecules help to kill zombie cells and protect neighbouring cells from premature ageing.
Flavonol Fisetin – for longer young skin
The accumulation of senescent fibroblasts, chronic inflammation and collagen alteration are typical changes in aging skin, which shows wrinkles, loss of elasticity, pigment spots.
As a study suggests (Takaya et al.), Flavonol Fisetin could stop and even reverse the effects of senescence-related changes and act as an anti-ageing substance on senescent fibroblasts in ageing skin. It selectively eliminated dermal fibroblasts in mouse/human skin models. The effect is based on inducing cell death through apoptosis.
Flavonol Fisetin -treated senescent skin grafts showed increased collagen density and a reduction in the senescence-associated secretory phenotype, including a reduction in matrix metalloproteinases and interleukins. No adverse effects were observed.
This flavonol is therefore a good candidate for slowing down skin aging by selectively removing senescent dermal fibroblasts and inhibiting SASP, and can be used as an innovative anti-aging active ingredient. In addition, it has a protective and supportive effect on mitochondria, the energy producers in the body.
Advantages and disadvantages of Flavonol Fisetin
Flavonol Fisetin , chemically described as 3,7,3‘,4’-tetrahydroxyflavone, has the structure of a diphenylpropane with two aromatic rings connected by an oxygen-containing heterocyclic ring. Its structure provides an indication of the molecule’s bioactivity and antioxidant properties.
With the keto group and the four OH groups, it is able to reduce inflammation.
Flavonol Fisetin has so far proven itself in studies on the prevention of neurodegenerative diseases, where its antioxidant, nitrosative and senolytic properties protect nerve cells from neuroinflammation, neurotoxicity and apoptotic degeneration and maintain mitochondrial functionality.
One disadvantage of Flavonol Fisetin with regard to its positive effects is its moderate bioavailability. This is due to its high lipophilicity, poor water solubility and rapid metabolism. Co-crystallisation with caffeine or nicotinamide could improve solubility. Bioavailability could be increased by liposomes and nanoemulsions.
Physical and chemical properties
Other names: Cotinine, 3,7,3‘,4’-tetrahydroxyflavone
Colour: yellow to ochre-yellow plant pigment
Molecular formula: C15H10O6
Molar mass: 286.2 g/mol
Density: 1.68 g/ml
Melting point: 330°C
Form: yellow needles
Physical state: solid
Solubility: low in water; insoluble in benzene, chloroform, ether; soluble in organic solvents such as alcohol, acetone, acetic acid, DMSO
Description; Finestin as an active cosmetic ingredient
INCI: Flavonol Fisetin
CAS no. 528-48-3
Effects: protects against oxidative and nitric stress (ROS / RNS), anti-inflammatory, antimicrobial, mitochondrial protection, senolytic effect (against zombie cells)
Formulations: liposomes, nanoemulsions, anti-ageing products for skin care and hair/scalp care
Recommended use concentration: 1 – 5%
Flavonol Fisetin : a promising option
Zombie cells and senolytic efficacy are terms that are gaining importance for innovative anti-aging responses in cosmetics.
Effective skin care against zombie cells relies on antioxidants, active ingredients that support the performance of mitochondria and the breakdown of aging cells: they have a senolytic effect. They should be used preventively, but could also reverse existing aging changes. Many studies confirm the effect of the plant pigment Flavonol Fisetin .
Cosmacon is taking on the challenge of using it in future-oriented skin care products.
We look forward to receiving your interested inquiries.
Also read our blog > Zombie cells
Literature
Lemaitre (2024). Looking for the philosopher’s stone: Emerging approaches to target the hallmarks of aging in the skin
Maher, Akaishi, Abe (2006) Flavonoid Flavonol Fisetin promotes ERK-dependent long-term potentiation and enhances memory
Takaya et al (2024) Flavonol Fisetin , a potential skin rejuvenation drug that eliminates senescent cells in the dermis
Yousefzadeh et al. (2018) Flavonol Fisetin is a senotherapeutic that extends health and lifespan
Zhu, Doornebal et al.(2017) New agents that target senescent cells: the flavone, Flavonol Fisetin , and the BCL-XL inhibitors, A1331852 and A1155463
Efficacy of FRO on Acne Vulgaris Pathogenesis.
Kim JE, Han H, Xu Y, Lee MH, Lee HJ.Pharmaceutics. 2023 Jul 4;15(7):1885
Senolytic drugs: from discovery to translation.
Kirkland JL, Tchkonia T.J Intern Med. 2020 Nov;288(5):518-536.
Flavonol Fisetin Promotes Hair Growth by Augmenting TERT Expression.
Kubo C, Ogawa M, Uehara N, Katakura Y.Front Cell Dev Biol. 2020 Oct 15;8:566617