Fisetin

Fisetin
IUPAC name 2-(3,4-dihydroxyphenyl)-3,7-dihydroxychromen-4-one
Other names Cotinin (not to be confused with Cotinine) 5-Desoxyquercetin Superfustel Fisetholz Fietin Fustel Fustet Viset Junger fustik
Identifiers
CAS number	528-48-3 Y
PubChem	5281614
ChemSpider	4444933 Y
DrugBank	DB07795
KEGG	C10041 Y
ChEBI	CHEBI:42567 Y
ChEMBL	CHEMBL31574 Y
Jmol-3D images	Image 1
SMILES O=C1c3c(O/C(=C1/O)c2ccc(O)c(O)c2)cc(O)cc3
InChI InChI=1S/C15H10O6/c16-8-2-3-9-12(6-8)21-15(14(20)13(9)19)7-1-4-10(17)11(18)5-7/h1-6,16-18,20H Y Key: XHEFDIBZLJXQHF-UHFFFAOYSA-N Y InChI=1/C15H10O6/c16-8-2-3-9-12(6-8)21-15(14(20)13(9)19)7-1-4-10(17)11(18)5-7/h1-6,16-18,20H Key: XHEFDIBZLJXQHF-UHFFFAOYAQ
Properties
Molecular formula	C15H10O6
Molar mass	286.2363 g/mol
Exact mass	286.047738
Melting point	330°C
Y (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Fisetin is a flavonol, a structurally distinct chemical substance that belongs to the flavonoid 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 in 1891.^[1]

Fisetin can be found in various plants such as Acacia greggii,^[2] Acacia berlandieri,^[2] in the yellow dye young fustic from Rhus cotinus (Eurasian smoketree), in Butea frondosa (parrot tree), Gleditschia triacanthos, Quebracho colorado, and the genus Rhus^[3] and in Callitropsis nootkatensis (yellow cypresses). Strawberries are a good food source of fisetin.^[4] It is also reported in mangoes.^{[citation needed]}

Biological activity

Fisetin is a potent sirtuin-activating compound (STAC),^[5] an agent that modulates sirtuins. Therefore, it is a caloric restriction mimetic candidate, a drug that has been shown to be able to alleviate aging effects in certain model organisms such as the yeast S. cerevisiae,^[5] the nematode C. elegans^[6] and the fruit fly Drosophila melanogaster.^[6] 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 studies have shown fisetin to exert anti-inflammatory^[7][8] and anti-carcinogenic^[9][10] effects in different lines of culture cells. 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.

Similar to many other flavonoids such as the structurally related flavonol quercetin, fisetin is a potent antioxidant. Its antioxidative activity may be due to its structural properties^[11] as well as to its ability to modulate certain cellular signalling pathways, especially protein kinase and lipid kinase pathways. For example, fisetin has been shown to induce the transcription factor Nrf2,^[12] leading to increased expression 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.^[4]

Side effects

Fisetin was, among other flavonoids, found to be a strong topoisomerase inhibitor.^[13] This effect may be responsible for both anticarcinogenic and carcinogenic potentials of the substance.^[14] Fisetin among other flavonoids is suspected to increase risk of infant leukemia (which is rare disease).^[15]

References

1. ^ Herzig, J. (1891). "Studien über Quercetin und seine Derivate, VII. Abhandlung [Studies on Quercetin and its Derivatives, Treatise VII]" (in German). Monatshefte für Chemie 12 (1): 177–90. doi:10.1007/BF01538594. 
2. ^ ^{a b} Forbes TDA, Clement BA. "Chemistry of Acacia's from South Texas" (PDF). Texas A&M Agricultural Research and Extension Center at. http://uvalde.tamu.edu/pdf/chemtdaf.pdf. Retrieved 2010-04-14. 
3. ^ Gábor, M.; Eperjessy, E. (1966). "Antibacterial Effect of Fisetin and Fisetinidin". Nature 212 (5067): 1273. doi:10.1038/2121273a0. PMID 21090477. 
4. ^ ^{a b} Maher, Pamela; Dargusch, Richard; Ehren, Jennifer L.; Okada, Shinichi; Sharma, Kumar; Schubert, David (2011). Deli, Maria A.. ed. "Fisetin Lowers Methylglyoxal Dependent Protein Glycation and Limits the Complications of Diabetes". PLoS ONE 6 (6): e21226. doi:10.1371/journal.pone.0021226. PMC 3124487. PMID 21738623. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3124487. Lay summary – ScienceDaily (June 28, 2011). 
5. ^ ^{a b} Howitz, Konrad T.; Bitterman, Kevin J.; Cohen, Haim Y.; Lamming, Dudley W.; Lavu, Siva; Wood, Jason G.; Zipkin, Robert E.; Chung, Phuong et al. (2003). "Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan". Nature 425 (6954): 191–6. doi:10.1038/nature01960. PMID 12939617. 
6. ^ ^{a b} Wood, Jason G.; Rogina, Blanka; Lavu, Siva; Howitz, Konrad; Helfand, Stephen L.; Tatar, Marc; Sinclair, David (2004). "Sirtuin activators mimic caloric restriction and delay ageing in metazoans". Nature 430 (7000): 686–9. doi:10.1038/nature02789. PMID 15254550. 
7. ^ Geraets, Liesbeth; Haegens, Astrid; Brauers, Karen; Haydock, Jane A.; Vernooy, Juanita H.J.; Wouters, Emiel F.M.; Bast, Aalt; Hageman, Geja J. (2009). "Inhibition of LPS-induced pulmonary inflammation by specific flavonoids". Biochemical and Biophysical Research Communications 382 (3): 598–603. doi:10.1016/j.bbrc.2009.03.071. PMID 19292976. 
8. ^ Park, Hyo-Hyun; Lee, Soyoung; Son, Hee-Young; Park, Seung-Bin; Kim, Mi-Sun; Choi, Eun-Ju; Singh, Thoudam S. K.; Ha, Jeoung-Hee et al. (2008). "Flavonoids inhibit histamine release and expression of proinflammatory cytokines in mast cells". Archives of Pharmacal Research 31 (10): 1303–11. doi:10.1007/s12272-001-2110-5. PMID 18958421. 
9. ^ Lim, D. Y.; Park, J. H. Y. (2009). "Induction of p53 contributes to apoptosis of HCT-116 human colon cancer cells induced by the dietary compound fisetin". AJP: Gastrointestinal and Liver Physiology 296 (5): G1060–8. doi:10.1152/ajpgi.90490.2008. 
10. ^ Khan, N.; Afaq, F.; Syed, D. N.; Mukhtar, H. (2008). "Fisetin, a novel dietary flavonoid, causes apoptosis and cell cycle arrest in human prostate cancer LNCaP cells". Carcinogenesis 29 (5): 1049–56. doi:10.1093/carcin/bgn078. PMC 2902387. PMID 18359761. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2902387. 
11. ^ Williams, Robert J; Spencer, Jeremy P.E; Rice-Evans, Catherine (2004). "Flavonoids: Antioxidants or signalling molecules?". Free Radical Biology and Medicine 36 (7): 838–49. doi:10.1016/j.freeradbiomed.2004.01.001. PMID 15019969. 
12. ^ Hanneken, A. (2006). "Flavonoids Protect Human Retinal Pigment Epithelial Cells from Oxidative-Stress-Induced Death". Investigative Ophthalmology & Visual Science 47 (7): 3164–77. doi:10.1167/iovs.04-1369. PMID 16799064. 
13. ^ Olaharski, A.J.; Mondrala, S.T.; Eastmond, D.A. (2005). "Chromosomal malsegregation and micronucleus induction in vitro by the DNA topoisomerase II inhibitor fisetin". Mutation Research/Genetic Toxicology and Environmental Mutagenesis 582 (1–2): 79–86. doi:10.1016/j.mrgentox.2005.01.002. PMID 15781213. 
14. ^ López-Lázaro, Miguel; Willmore, Elaine; Austin, Caroline A. (2010). "The dietary flavonoids myricetin and fisetin act as dual inhibitors of DNA topoisomerases I and II in cells". Mutation Research/Genetic Toxicology and Environmental Mutagenesis 696 (1): 41–7. doi:10.1016/j.mrgentox.2009.12.010. PMID 20025993. 
15. ^ Spector, L. G.; Xie, Y; Robison, LL; Heerema, NA; Hilden, JM; Lange, B; Felix, CA; Davies, SM et al. (2005). "Maternal Diet and Infant Leukemia: The DNA Topoisomerase II Inhibitor Hypothesis: A Report from the Children's Oncology Group". Cancer Epidemiology Biomarkers & Prevention 14 (3): 651–5. doi:10.1158/1055-9965.EPI-04-0602. PMID 15767345.