Fisetin

Fisetin is a flavonoid, a subgroup of phytochemicals. It can be found in various fruits and vegetables, but also in wine and chocolate. In this article, we will show you the exciting research and background of the molecule. We will explain to you, for example, why fisetin is used in science to eliminate so-called "zombie cells".

What effects does Fisetin have?

Due to its molecular structure, fisetin has the ability to neutralize free radicals. This makes it a natural antioxidant, similar to other phytochemicals. In addition, the molecule can increase the amount of glutathione, the most powerful antioxidant in many organisms.

In addition, it interacts with some inflammatory signaling pathways and has repeatedly been shown to produce anti-inflammatory properties in cell studies.

Where is fisetin found in food?

It occurs naturally in a variety of foods. In larger quantities, the substance is found in strawberries, which makes this fruit one of the best natural sources of this flavonoid. In addition, fisetin is found in other fruits such as apples and mangoes, as well as in vegetables such as tomatoes, onions and cucumbers.

It is also found in manageable quantities in nuts and seeds as well as in wine and dark chocolate. Some spices, including turmeric and ginger, also contain fisetin.

Because the levels of fisetin in foods vary, it's important to consume a variety of foods to ensure you're getting an adequate amount of this beneficial flavonoid. It's also worth noting that fisetin is sensitive to heat, so raw or minimally processed foods tend to have higher levels of this nutrient.

How much fisetin is in food?

Depending on the database, you get slightly different results on this question. To give you a better overview, we have summarized some of the foods with the highest content of fisetin. This study provides the basis for the table:

Fisetin, quercetin and luteolin.

The three molecules, fisetin, quercetin and luteolin , are all secondary plant substances. To give you a better overview of which molecule is present in which fruits and vegetables, we have created another table for you here. The data comes from this study.

The current research situation

At present, research into Fisetin is still based on animal studies, but the first studies are already being carried out on humans. We show you the areas of science in which Fisetin is being researched:

Alzheimer

Alzheimer's disease is a serious and chronic disease of the brain characterized by the deposition of a substance called amyloid beta and the excessive phosphorylation of proteins called tau in the brain. This accumulation leads to problems with brain function, especially memory and cognition.

In a study in mice, researchers looked at the protective effect of fisetin on the brains of mice, particularly in the context of Alzheimer's disease. They used a model of Alzheimer's disease in which the mice were injected with amyloid beta. This injection led to the well-known memory and synapse problems, as well as inflammation in the brain and the degeneration of neurons.

The mice were then treated with fisetin, which was injected into the body (not directly into the brain). This treatment began one day after the amyloid beta injection and lasted for two weeks. The researchers found that the molecule significantly reduced the accumulation of amyloid beta as well as the hyperphosphorylation of tau proteins in the mouse brain. In addition, it contributed to the improvement of synaptic function, which led to an improvement in the memory performance of the mice.

The treatment also activated pathways in the mice's brains that helped counteract the effects of amyloid beta.

Inhibition of inflammatory factors

To find out what properties fisetin has, the scientists carried out cell culture studies. This is basic research to better understand the biochemical relationships between the molecules. It is important to note that these studies initially only represent the basics of how molecules are likely to work.

So what did the scientists find out about fisetin in the cell culture studies? Fisetin interacts in cell culture studies via several pathways: It can reduce the production of pro-inflammatory cytokines and chemokines. In addition, fisetin can inhibit the activity of enzymes involved in inflammatory processes, such as cyclooxygenase-2 (COX-2) and lipoxygenase (LOX), which are responsible for the production of inflammatory mediators.

Another mechanism by which fisetin could exert its anti-inflammatory effects is by modulating signaling pathways involved in inflammatory responses. In cell cultures, fisetin appears to inhibit the activation of NF-kB (nuclear factor kappa B), an important regulator of the inflammatory response, and modulate the activity of signaling pathway proteins such as MAP kinases and PI3K/Akt, which are involved in inflammatory processes .

In addition, fisetin has been shown to regulate the activity of inflammatory cells such as macrophages and neutrophils by reducing the release of inflammatory mediators such as nitric oxide (NO) and prostaglandins.

Fisetin & Longevity

In studies with mice, administration of fisetin in late life resulted in a restoration of tissue homeostasis, a reduction in age-related pathologies, and an increase in mean and maximum lifespan.

Even when given to rodents equivalent to 75 human years, fisetin was able to extend lifespan by 10%. These results can probably be attributed to the effect of fisetin on the Hallmarks of Aging. The researchers were able to demonstrate that fisetin has a life-prolonging effect not only in mice, but also in flies and worms. The life-prolonging effect in the animal studies is probably due to the activation of the sirtuins. This family of genes, also known as longevity genes, is the focus of ageing research. Other molecules that also belong to the sirtuin activators are, for example, resveratrol, which David Sinclair researched.

To help you better understand the molecular background, we will use the example of cellular senescence to show you how fisetin affects longevity in animal experiments.

Senescence

Before we introduce you to the molecular interaction of fisetin, let's first explain the concept of senescence and senolysis. To put it simply, senescence refers to old cells that no longer divide and remain in a kind of intermediate state – not really dead, but not really alive either. Hence the nickname "zombie cells". You can learn more about these special cells and what they have to do with aging in our senescence article.

We find these senescent cells in our body at every stage of life and under certain circumstances they can even be useful. In old age, however, too many of these "zombie cells" are likely to accumulate and the body can no longer keep up with the elimination, the senolysis, of these cells. This increase in senescent cells leads to the activation of tissue hormones and messenger substances, which are summarized under the name SAPS. Animal studies in particular have shown that the elimination of "zombie cells" leads to a longer and healthier life. The molecules that can help the body to detect and eliminate such "zombie cells" are called senolytics.

Senolytics - the weapon against the "zombie cells"

Senolytic therapy, which aims to selectively eliminate senescent cells, has attracted a lot of attention in recent years. Much of this is still theory and has only been tested on animals.

According to this paper, the senolytic potency of fisetin is higher than that of comparable flavonoids. A study showed that fisetin was able to destroy senescent cells in old mice and improve both their health and lifespan.

One of the molecular mechanisms behind the extension of lifespan in the animal experiments is thought to be the DAF-16-induced stress response and induced autophagy.   Altered autophagy is one of the hallmarks of aging, and a reversal of this could thus be one of the molecular reasons for the effects of fisetin in longevity research.

Did you know? Autophagy is the body's ability to eliminate "old cells", as happens during fasting, for example.

Side effects of fisetin

Fisetin is generally considered to be well tolerated. As with all supplements, side effects can occur, especially at higher dosages. These include:

• Gastrointestinal complaints: Some people may experience gastrointestinal problems such as stomach pain, nausea, or diarrhea after taking fisetin supplements .
• Allergic reactions: Although rare, it is possible for individuals to have an allergic reaction to fisetin. Symptoms of an allergic reaction may include a rash, itching, difficulty breathing, and swelling of the face or neck.
• Drug interactions: Fisetin could potentially interact with certain medications, especially those that affect blood clotting, such as blood thinners (anticoagulants). This could increase the risk of bleeding.

Conclusion

Fisetin is a versatile and exciting molecule from the flavonoid group. It is being researched for its senolytic properties. Fisetin is still mainly the subject of basic research, but this will certainly change in the near future.