Fisetin is a flavonol, a structurally distinct chemical substance that belongs to the flavonoid

Flavonoid

Flavonoids , are a class of plant secondary metabolites....

 group of polyphenols. It can be found in many plants, where it serves as a colouring agent. Its chemical formula was first described by Austrian chemist Josef Herzig

Josef Herzig

Josef Herzig was an Austrian chemist.Herzig was born in Sanok, Galicia, which at that time was part of Austria-Hungary. Herzig went to school in Breslau until 1874, started studying chemistry at the University of Vienna but joined August Wilhelm von Hofmann at the University of Berlin in the...

 in 1891.

Fisetin can be found in various plants such as Acacia greggii

Acacia greggii

Acacia greggii is a species of Acacia native to the southwestern United States and northern Mexico, from the extreme south of Utah south through southern Nevada, southeast California, Arizona, New Mexico and western Texas to Baja California, Sinaloa and Nuevo León in...

, Acacia berlandieri

Acacia berlandieri

Acacia berlandieri is a shrub native to the Southwestern United States and northeast Mexico that belongs to the subfamily Mimosoideae of Fabaceae . It grows tall, with blossoms that are spherical and white, occurring from February through April...

, in the yellow dye young fustic from Rhus cotinus (Eurasian smoketree

Eurasian smoketree

The Eurasian smoketree, smoke tree, or Purple smoke bush is native to a large area from southern Europe, east across central Asia and the Himalaya to northern China....

), in Butea frondosa (parrot tree), Gleditschia triacanthos, Quebracho colorado, and the genus Rhus and in Callitropsis nootkatensis (yellow cypresses). Strawberries

Strawberry

Fragaria is a genus of flowering plants in the rose family, Rosaceae, commonly known as strawberries for their edible fruits. Although it is commonly thought that strawberries get their name from straw being used as a mulch in cultivating the plants, the etymology of the word is uncertain. There...

 are a good food source of fisetin. It is also reported in mango

Mango

The mango is a fleshy stone fruit belonging to the genus Mangifera, consisting of numerous tropical fruiting trees in the flowering plant family Anacardiaceae. The mango is native to India from where it spread all over the world. It is also the most cultivated fruit of the tropical world. While...

es.

Biological activity

Fisetin is a potent sirtuin-activating compound

Sirtuin-activating compound

Sirtuin-activating compounds are chemical compounds having an effect on sirtuins, a group of enzymes that use NAD+ to remove acetyl groups from proteins. They are caloric restriction mimetic candidates, molecules able to prevent aging-related diseases like Alzheimer's , diabetes, and...

 (STAC), an agent that modulates sirtuin

Sirtuin

Sirtuin or Sir2 proteins are a class of proteins that possess either histone deacetylase or mono-ribosyltransferase activity. Sirtuins regulate important biological pathways in bacteria, archaea and eukaryotes...

s. Therefore, it is a caloric restriction mimetic candidate, a drug that has been shown to be able to alleviate aging effects in certain model organism

Model organism

A model organism is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the organism model will provide insight into the workings of other organisms. Model organisms are in vivo models and are widely used to...

s such as the yeast

Yeast

Yeasts are eukaryotic micro-organisms classified in the kingdom Fungi, with 1,500 species currently described estimated to be only 1% of all fungal species. Most reproduce asexually by mitosis, and many do so by an asymmetric division process called budding...

 S. cerevisiae

Saccharomyces cerevisiae

Saccharomyces cerevisiae is a species of yeast. It is perhaps the most useful yeast, having been instrumental to baking and brewing since ancient times. It is believed that it was originally isolated from the skin of grapes...

, the nematode

Nematode

The nematodes or roundworms are the most diverse phylum of pseudocoelomates, and one of the most diverse of all animals. Nematode species are very difficult to distinguish; over 28,000 have been described, of which over 16,000 are parasitic. It has been estimated that the total number of nematode...

 C. elegans

Caenorhabditis elegans

Caenorhabditis elegans is a free-living, transparent nematode , about 1 mm in length, which lives in temperate soil environments. Research into the molecular and developmental biology of C. elegans was begun in 1974 by Sydney Brenner and it has since been used extensively as a model...

 and the fruit fly

Drosophila

Drosophila is a genus of small flies, belonging to the family Drosophilidae, whose members are often called "fruit flies" or more appropriately pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species to linger around overripe or rotting fruit...

 Drosophila melanogaster

Drosophila melanogaster

Drosophila melanogaster is a species of Diptera, or the order of flies, in the family Drosophilidae. The species is known generally as the common fruit fly or vinegar fly. Starting from Charles W...

. Whether such effects can be replicated in humans is currently still not entirely clear and remains an issue of scientific research and debate.

Aside from its effects on aging, various in vitro

In vitro

In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...

studies have shown fisetin to exert anti-inflammatory

Inflammation

Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...

 and anti-carcinogenic

Carcinogenesis

Carcinogenesis or oncogenesis is literally the creation of cancer. It is a process by which normal cells are transformed into cancer cells...

 effects in different lines of culture cells

Cell culture

Cell culture is the complex process by which cells are grown under controlled conditions. In practice, the term "cell culture" has come to refer to the culturing of cells derived from singlecellular eukaryotes, especially animal cells. However, there are also cultures of plants, fungi and microbes,...

. However, because in vitro experiments do not or only incompletely mimic the metabolisation fisetin undergoes in the body, they may not accurately reflect the actual effects of fisetin in vivo

In vivo

In vivo is experimentation using a whole, living organism as opposed to a partial or dead organism, or an in vitro controlled environment. Animal testing and clinical trials are two forms of in vivo research...

.

Similar to many other flavonoids such as the structurally related flavonol quercetin

Quercetin

Quercetin , a flavonol, is a plant-derived flavonoid found in fruits, vegetables, leaves and grains. It also may be used as an ingredient in supplements, beverages or foods.-Occurrence:...

, fisetin is a potent antioxidant

Antioxidant

An antioxidant is a molecule capable of inhibiting the oxidation of other molecules. Oxidation is a chemical reaction that transfers electrons or hydrogen from a substance to an oxidizing agent. Oxidation reactions can produce free radicals. In turn, these radicals can start chain reactions. When...

. Its antioxidative activity may be due to its structural properties as well as to its ability to modulate certain cellular signalling pathways, especially protein kinase

Protein kinase

A protein kinase is a kinase enzyme that modifies other proteins by chemically adding phosphate groups to them . Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins...

 and lipid kinase pathways. For example, fisetin has been shown to induce the transcription factor

Transcription factor

In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...

 Nrf2, leading to increased expression

Gene expression

Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...

 of several protective and antioxidative genes.

One study at the Salk Institute found that fisetin may help improve memory and protect the brain from the onset of Alzheimer's disease and also that it may be useful for reducing kidney failure in diabetics.

Side effects

Fisetin was, among other flavonoid

Flavonoid

Flavonoids , are a class of plant secondary metabolites....

s, found to be a strong topoisomerase inhibitor

Topoisomerase inhibitor

Topoisomerase inhibitors are agents designed to interfere with the action of topoisomerase enzymes , which are enzymes that control the changes in DNA structure by catalyzing the breaking and rejoining of the phosphodiester backbone of DNA strands during the normal cell cycle.In recent years,...

. This effect may be responsible for both anticarcinogenic and carcinogenic potentials of the substance. Fisetin among other flavonoid

Flavonoid

Flavonoids , are a class of plant secondary metabolites....

s is suspected to increase risk of infant leukemia (which is rare disease).