Flavonoid

Kutipan By : Fahry Marewo4
From Wikipedia, the free encyclopedia

Flavonoids (or bioflavonoids) are a class of plant secondary metabolites. According to the IUPAC nomenclature,[1] they can be classified into:
•flavonoids, derived from 2-phenylchromen-4-one (2-phenyl-1,4-benzopyrone) structure
•isoflavonoids, derived from 3-phenylchromen-4-one (3-phenyl-1,4-benzopyrone) structure
•neoflavonoids, derived from 4-phenylcoumarine (4-phenyl-1,2-benzopyrone) structure.
Flavonoids are most commonly known for their antioxidant activity. Flavonoids are also commonly referred to as bioflavonoids in the media – the terms are largely equivalent and interchangeable, for most flavonoids are biological in origin. Flavonoids are "the most common group of polyphenolic compounds in the human diet and are found ubiquitously in plants".[2]

Struktur molekular kerangka flavone ( 2-phenyl-1,4-benzopyrone)

Flavonoids (atau bioflavonoids) adalah kelas dari metabolit sekunder tumbuhan. Menurut nomenklatur IUPAC, flavonoids dapat digolongkan ke dalam :

1.Flavonoids, turunan dari struktur 2-phenylchromen-4-one ( 2-phenyl-1,4-benzopyrone)
2.Isoflavonoids, turunan dari struktur 3-phenylchromen-4-one ( 3-phenyl-1,4-benzopyrone)
3.Neoflavonoids, turunan dari struktur 4-phenylcoumarine ( 4-phenyl-1,2-benzopyrone).

Flavonoids paling umum dikenal karena aktivitas antioxidantnya. Flavonoids biasanya juga dikenal sebagai bioflavonoids pada media - istilah padanan umum dan dapat bertukar tempat. Flavonoids secara umum termasuk dalam kelompok polyphenolic pada diet manusia dan ditemukan pada sebagian besar dari tumbuhan (Spencer, Jp 2008).

Flavonoid merupakan komponen yang ditemukan dalam buah, sayuran, dan beberapa organisme yang mengandung senyawa biokimia penting dan memiliki efek antiosidan. Flavonoid merupakan komponen polifenolic yang dapat ditemukan secara alami dan dikategorisasi berdasarkan struktur kimia, kedalam flavonol, flavon, flavonones, isoflavon, catechin, anthocyanidine, dan chalcones. Lebih dari 4000 flavonoid telah diidentifkasi, kebanyakan ditemukan dalam buah, sayuran dan biji-bijian (teh, kopi, beer, wine, dan minuman buah). Flavonoid dianggap penting karena mempunyai konstribusi pada kesehatan manusia seperti yang telah dilaporkan bahwa flavonoid berpotensial sebagai antiviral, antiallergic, antiplatelet, anti-inflammatory, antitumor, dan antioksidan.

Biosynthesis
Flavonoids are synthesized by the phenylpropanoid metabolic pathway in which the amino acid phenylalanine is used to produce 4-coumaroyl-CoA[3]. This can be combined with malonyl-CoA to yield the true backbone of flavonoids, a group of compounds called chalcones, which contain two phenyl rings (see polyphenols). Conjugate ring-closure of chalcones results in the familiar form of flavonoids, the three-ringed structure of a flavone. The metabolic pathway continues through a series of enzymatic modifications to yield flavanones → dihydroflavonols → anthocyanins. Along this pathway, many products can be formed, including the flavonols, flavan-3-ols, proanthocyanidins (tannins) and a host of other various polyphenolics.

Biosynthesis
Flavonoids disintesis oleh jalur metabolisme phenylpropanoid di mana asam amino phenylalanine digunakan untuk memproduksi 4-coumaroyl-CoA (Ververidis Filippos, et. al,. 2007). Ini dapat dikombinasikan dengan malonyl-CoA untuk menghasilkan kerangka yang sebenarnya dari flavonoids, suatu kelompok campuran yang disebut dengan chalcones, yang berisi dua cincin fenil. Konjugasi dari cincin penutup chalcones mengakibatkan format yang umum dikenal flavonoids, struktur tiga cincin dari flavone. Jalur metabolisme selanjutnya melalui suatu rangkaian dari modifikasi enzymatik untuk menghasilkan flavanones → dihydroflavonols → anthocyanins. Sepanjang jalur ini, banyak produk yang dapat dibentuk, termasuk flavonols, flavan-3-ols, proanthocyanidins (tannins) dan sejumlah besar jenis polyphenolics.

Biological effects
Flavonoids are widely distributed in plants fulfilling many functions including producing yellow or red/blue pigmentation in flowers and protection from attack by microbes and insects. The widespread distribution of flavonoids, their variety and their relatively low toxicity compared to other active plant compounds (for instance alkaloids) mean that many animals, including humans, ingest significant quantities in their diet. Flavonoids have been referred to as "nature's biological response modifiers" because of strong experimental evidence of their inherent ability to modify the body's reaction to allergens, viruses, and carcinogens. They show anti-allergic, anti-inflammatory[4] , anti-microbial[5] and anti-cancer activity.
Consumers and food manufacturers have become interested in flavonoids for their medicinal properties, especially their potential role in the prevention of cancers and cardiovascular disease. The beneficial effects of fruit, vegetables, and tea or even red wine have been attributed to flavonoid compounds rather than to known nutrients and vitamins[6].

Efek Biologi
Flavonoids secara luas terbagi dalam banyak fungsi tumbuhan termasuk memproduksi pigmentasi kuning atau merah/biru pada bunga dan perlindungan dari serangan mikroba dan serangga. Distribusi yang luas ri dflavonoids, variasi dan hubunganya toksisitas yang rendah dibandingkan dengan kandungan aktifnya pada tumbuhan (contohnya alkaloids) rata-rata pada kebanyakan hewan, termasuk manusia, jumlah yang signifikan dalam pencernaan pada diet mereka. Flavonoids dikenal sebagai " modifikasi respon biologi alami " karena terbukti kuat secara eksperimental flavonoids tidak bisa dipisahkan dari kemampuan untuk memodifikasi reaksi tubuh pada penyebab alergi, virus, dan segala penyebab kanker (carcinogens). Mereka menunjukkan aktivitas anti-allergic, anti-inflammatory (Yamamoto and Gaynor, 2007), anti-microbial (Cushnie TPT, Lamb AJ 2005), dan anti-cancer.
Konsumen dan pabrik makanan olahan menjadi tertarik akan flavonoids untuk bahan obat, terutama potensi flavonoisd dalam pencegahan kanker dan penyakit kardiovasculer. Efek yang menguntungkan dari buah, sayur, dan teh atau bahkan anggur merah telah dihubungkan dengan kandungan flavonoid dibandingkan dengan gizi dan vitamins (Félicien Breton (2008).

Health benefits aside from antioxidant values
In 2007, research conducted at the Linus Pauling Institute and published in Free Radical Biology and Medicine indicates that inside the human body, flavonoids themselves are of little or no direct antioxidant value [7]. Body conditions prove to be unlike controlled test tube conditions, and the flavonoids are poorly absorbed (less than 5%), with most of what is absorbed being quickly metabolized and excreted.
The huge increase in antioxidant capacity of blood seen after the consumption of flavonoid-rich foods is not caused directly by the flavonoids themselves, but most likely is due to increased uric acid levels that result from expelling flavonoids from the body.[8] According to Frei, "we can now follow the activity of flavonoids in the body, and one thing that is clear is that the body sees them as foreign compounds and is trying to get rid of them.

Manfaat Kesehatan Selain antioxidant

Pada 2007, riset yang diselenggarakan di Linus Pauling Institut dan diterbitkan dalam Free Radical Biology and Medicine menunjukkan bahwa di dalam tubuh manusia, flavonoids hanya sedikit atau tidak ada nilai antioxidant langsung (Lotito SB, Frei B 2006). Kondisi tubuh membuktikan menjadi tidak sama dengan uji kondisi tabung dikendalikan, dan flavonoids sangat sedikit diserap (kurang dari 5%), dengan kebanyakan dari apa yang diserap dengan cepat dikeluarkan dan dimetabolis.
Peningkatan yang sangat besar dalam kapasitas dari antioxidant darah terlihat setelah konsumsi makanan yang kayak an flavonoid tidak disebabkan secara langsung oleh flavonoids tersebut, tetapi hampir bisa dipastikan adalah berkaitan dengan peningkatan level asam uric yang diakibatkan oleh terusirnya flavonoids dari tubuh. (David Stauth, 2006)

Cancer
The process of gearing up to get rid of unwanted compounds is inducing so-called Phase II enzymes that also help eliminate mutagens and carcinogens, and therefore may be of value in cancer prevention. Flavonoids could also induce mechanisms that help kill cancer cells and inhibit tumor invasion."[8] UCLA cancer researchers have found that study participants who ate foods containing certain flavonoids seemed to be protected from developing lung cancer. Dr. Zuo-Feng Zhang, of the UCLA's Jonsson Cancer Center and a professor of public health and epidemiology at the UCLA School of Public Health said the flavonoids that appeared to be the most protective included catechin, found in strawberries and green and black teas; kaempferol, found in brussel sprouts and apples; and quercetin, found in beans, onions and apples.[9]
Their research also indicated that only small amounts of flavonoids are necessary to see these medical benefits. Taking large dietary supplements provides no extra benefit and may pose some risks.[8]

Kanker
Proses dari pemasangan bahan yang masuk mendapatkan dari kandungan yang tak dikehendaki adalah berpengaruh, yang disebut enzim Tahap II yang juga membantu mengurangi mutagens dan segala penyebab kanker, dan oleh karena itu mungkin bermanfaat dalam pencegahan kanker. Flavonoids dapat juga mempengaruhi mekanisme yang membantu pembunuhan sel kanker dan menghalangi invasi tumor (David Stauth, 2006) Para peneliti kanker dari UCLA sudah menemukan study yang membantu bahwa makanan yang mengandung flavonoids tertentu menunjukan mampu melindungi dari perkembangan kanker paru-paru. Dr. Zuo-Feng Zhang, dari UCLA's Jonsson Cancer Center dan profesor kesehatan masyarakat dan epidemiologi di mengakatan bahwa flavonoids yang muncul tersebut yang kebanyakan bersifat melindungi termasuk catechin, yang ditemukan dalam strawberry dan teh hitam dan hijau; kaempferol, yang ditemukan dalam kecambah brussel dan buah apel; dan quercetin, yang ditemukan dalam kacang, bawang dan apel.(UCLA news May 2008).
Riset mereka juga menunjukkan bahwa hanya sejumlah kecil flavonoids yang diperlukan untuk melihat manfaat medis ini. Pengambilan suplemen makanan yang besar tidak menyediakan apapun manfaat ekstra dan dapat memperlihatkann beberapa resiko (David Stauth, 2006)

Diarrhea
A study done at Children's Hospital & Research Center Oakland, in collaboration with scientists at Heinrich Heine University in Germany, has shown that epicatechin, quercetin and luteolin can inhibit the development of fluids that result in diarrhea by targeting the intestinal cystic fibrosis transmembrane conductance regulator Cl– transport inhibiting cAMP-stimulated Cl– secretion in the intestine.[10]

Diarrhea
Suatu studi yang dilakukan pada Rumah sakit Anak-Anak & Pusat Riset Oakland, bekerjasama dengan ilmuwan pada Heinrich Heine University di Jerman, telah menunjukkan epicatechin, quercetin dan luteolin itu dapat menghalangi pengembangan cairan yang mengakibatkan diarrhea dengan mengarahkan fibrosis cystic transmembrane pengatur konduktans Cl- mengangkut menghambat cAMP- yang distimulasi - Pengeluaran Cl didalam usus.(Schuier M, Sies H, Illek B, Fischer H, 2005).

Important flavonoids
Quercetin
Main article: quercetin
Quercetin is a flavonoid and, to be more specific, a flavonol. It is the aglycone form of a number of other flavonoid glycosides, such as rutin and quercitrin, found in citrus fruit, buckwheat and onions. Quercetin forms the glycosides quercitrin and rutin together with rhamnose and rutinose, respectively. It may also help to prevent some types of cancer, however currently there is more research needed in this area.
Quercetin adalah suatu flavonoid dan, untuk lebih spesifik, suatu flavonol. Itu adalah bentuk aglycone sejumlah lain dari flavonoid glycosides, seperti rutin dan quercitrin, yang ditemukan dalam buah jeruk, gandum dan bawang. Bentuk quercetin yaitu glycosides quercitrin dan rutin bersama-sama dengan rhamnose dan rutinose, secara berturut-turut. Mungkin juga membantu untuk mencegah beberapa bentuk kanker, sekarang ini membutuhkan lebih banyak riset pada wilayah ini.

Epicatechin

Epicatechin improves blood flow and thus seems good for cardiac health. Cocoa, the major ingredient of dark chocolate, contains relatively high amounts of epicatechin and has been found to have nearly twice the antioxidant content of red wine and up to three times that of green tea in in-vitro tests.[11] [12] But in the test outlined above it now appears the beneficial antioxidant effects are minimal as the antioxidants are rapidly excreted from the body.
Epicatechin meningkatkan peredaran darah dan dengan begitu baik untuk kesehatan jantung. Cocoa, kandungan utama dari coklat gelap, berisi epicatechin yang tinggi dan telah ditemukan hampir dua kali lebih dari kandungan antioxidant anggur merah dan lebih dari] tiga kali dari teh hijau dalam uji in-vitro (Lee KW, Kim YJ, Lee HJ, Lee CY 2003). Tetapi pada uji yang diuraikan di atas sekarang terlihat efek antioxidant yang menguntungkan minimal seperti antioxidants yang dikeluarkan dengan cepat dari tubuh.

Oligomeric proanthocyanidins
Proanthocyanidins extracts demonstrate a wide range of pharmacological activity. Their effects include increasing intracellular vitamin C levels, decreasing capillary permeability and fragility, scavenging oxidants and
free radicals, and inhibiting destruction of collagen, the most abundant protein in the body.
Oligomeric Proanthocyanidins
Ekstrak Proanthocyanidins mempertunjukkan suatu cakupan luas dari aktivitas pharmakologis. Efeknya meliputi peningkatan jumlah intracellular vitamin C, mengurangi permeabilitas kapiler dan kerapuhan, pencarian oxidants dan radikal bebas, dan penghambatan kerusakan dari collagen, protein yang paling berlimpah di dalam tubuh.

Important dietary sources
Good sources of flavonoids include all citrus fruits, berries, ginkgo biloba, onions[13][14], parsley[15], pulses[16], tea (especially white and green tea), red wine, seabuckthorn, and dark chocolate (with a cocoa content of seventy percent or greater). (Tsushida T., Suzuki, M. 1996)

Sumber diet yang penting
Sumber flavonoids yang baik meliputi semua buah jeruk, biji, ginkgo biloba, bawang (Tsushida T., Suzuki, M. 1996), parsley (Justesen U, Knuthsen P 2001). pulses (Ewald C, Fjelkner-Modig S, Johansson K, Sjöholm I, Åkesson B 1999). teh (terutama teh putih dan hijau), anggur merah, seabuckthorn, dan coklat gelap (dengan isi cocoa tujuh puluh persen atau lebih besar).

Citrus

The citrus bioflavonoids include hesperidin (a glycoside of the flavanone hesperetin), quercitrin, rutin (two glycosides of the flavonol quercetin), and the flavone tangeritin. In addition to possessing antioxidant activity and an ability to increase intracellular levels of vitamin C, rutin and hesperidin exert beneficial effects on capillary permeability and blood flow. They also exhibit some of the anti-allergy and anti-inflammatory benefits of quercetin. Quercetin can also inhibit reverse transcriptase, part of the replication process of retroviruses.[17] The therapeutical relevance of this inhibition has not been established. Hydroxyethylrutosides (HER) have been used in the treatment of capillary permeability, easy bruising, hemorrhoids, and varicose veins.
Ginkgo
Leaf extract from the Ginkgo tree is widely marketed as an herbal supplement. The active ingredients are flavoglycosides.

Tea

Bai Hao Yinzhen from Fuding in Fujian Province, widely considered the best grade of white tea

Green tea flavonoids are potent antioxidant compounds, thought to reduce incidence of cancer and heart disease. The major flavonoids in green tea are the kaempferol and catechins (catechin, epicatechin, epicatechin gallate, and epigallocatechin gallate (EGCG)).
In producing teas such as oolong tea and black tea, the leaves are allowed to oxidize, during which enzymes present in the tea convert some or all of the catechins to larger molecules. However, green tea is produced by steaming the fresh-cut leaf, which inactivates these enzymes, and oxidation does not significantly occur. White tea is the least processed of teas and is shown to present the highest amount of catechins known to occur in camellia sinensis.

Wine
See also: Phenolic compounds in wine
Grape skins contain significant amounts of flavonoids as well as other polyphenols[18]. Both red and white wine contain flavonoids; however, since red wine is produced by fermentation in the presence of the grape skins, red wine has been observed to contain higher levels of flavonoids, and other polyphenolics such as resveratrol.
Dark chocolate
Flavonoids exist naturally in cacao, but because they can be bitter, they are often removed from chocolate, even the dark variety[19].
Subgroups
Over 5000 naturally occurring flavonoids have been characterized from various plants. They have been classified according to their chemical structure, and are usually subdivided into the following subgroups (for further reading see [3]):
Sub-Sub kelompok
Lebih dari 5000 flavonoids terjadi secara alami telah ditandai dari berbagai tumbuhan. Flavonoids telah digolongkan menurut struktur kimianya, dan pada umumnya dibagi lagi ke dalam sub-sub kelompok berikut :
Flavones
Flavones are divided into four groups:[20]
Flavones dibagi menjadi empat groups:[20]

Isoflavones
•Isoflavones
Isoflavones use the 3-phenylchromen-4-one skeleton (with no hydroxyl group substitution on carbon at position 2).
Examples: Genistein, Daidzein, Glycitein
Isoflavones menggunakan 3-phenylchromen-4-one rangka ( dengan tidak ada penggantian kelompok hidroksit atas karbon pada posisi 2).
Contoh: Genistein, Daidzein, Glycitein
Flavan-3-ols, Proanthocyanadins, and Anthocyanidins
•Flavan-3-ols (also known as Flavanols) and Proanthocyanidins
Flavan-3-ols use the 2-phenyl-3,4-dihydro-2H-chromen-3-ol skeleton.
Catechins (Catechin (C), Gallocatechin (GC), Catechin 3-gallate (Cg), Gallocatechin 3-gallate (GCg)), Epicatechins (Epicatechin (EC), Epigallocatechin (EGC), Epicatechin 3-gallate (ECg), Epigallocatechin 3-gallate (EGCg))
Proanthocyanidins are dimers, trimers, oligomers, or polymers of the flavanols.
•Anthocyanidins
Anthocyanidins are the aglycones of anthocyanins. Anthocyanidins use the flavylium (2-phenylchromenylium) ion skeleton
Examples: Cyanidin, Delphinidin, Malvidin, Pelargonidin, Peonidin, Petunidin

Availability through microorganisms
A number of recent research articles have demonstrated the efficient production of flavonoid molecules from genetically-engineered microorganisms[21][22].
See also

References
1.^ Flavonoids (isoflavonoids and neoflavonoids)., IUPAC Compendium of Chemical Terminology
2.^ Spencer, Jp (May 2008). "Flavonoids: modulators of brain function?". The British journal of nutrition 99 E Suppl 1: ES60–77. doi:10.1017/S0007114508965776. ISSN 0007-1145. PMID 18503736. edit
3.^ a b Ververidis Filippos; Trantas Emmanouil, Douglas Carl, Vollmer Guenter, Kretzschmar Georg, Panopoulos Nickolas (October 2007). "Biotechnology of flavonoids and other phenylpropanoid-derived natural products. Part I: Chemical diversity, impacts on plant biology and human health". Biotechnology Journal 2 (10): 1214. doi:10.1002/biot.200700084.
4.^ "Therapeutic potential of inhibition of the NF-κB pathway in the treatment of inflammation and cancer". Yamamoto and Gaynor 107 (2): 135 -- Journal of Clinical Investigation. http://www.jci.org/cgi/content/full/107/2/135?ijkey=a1e09ce2dbca283cec170598f2410b15d5f4304f&keytype2=tf_ipsecsha.
5.^ Cushnie TPT, Lamb AJ (2005). "Antimicrobial activity of flavonoids". International Journal of Antimicrobial Agents 26 (5): 343–356. doi:10.1016/j.ijantimicag.2005.09.002. PMID 16323269.
6.^ Félicien Breton (2008). "Health benefits of oligomeric proanthocyanidins". http://www.frenchscout.com/polyphenols#procyanidins.
7.^ Lotito SB, Frei B (2006). "Consumption of flavonoid-rich foods and increased plasma antioxidant capacity in humans: cause, consequence, or epiphenomenon?". Free Radic. Biol. Med. 41 (12): 1727–46. doi:10.1016/j.freeradbiomed.2006.04.033. PMID 1715775.
8.^ a b c "Studies force new view on biology of flavonoids", by David Stauth, EurekAlert!. Adapted from a news release issued by Oregon State University. URL accessed .
9.^ UCLA news May 2008 - Fruits, vegetables, teas may protect smokers from lung cancer
10.^ Schuier M, Sies H, Illek B, Fischer H (01 October 2005). "Cocoa-related flavonoids inhibit CFTR-mediated chloride transport across T84 human colon epithelia". J. Nutr. 135 (10): 2320–5. PMID 16177189. http://jn.nutrition.org/cgi/reprint/135/10/2320.
11.^ Lee KW, Kim YJ, Lee HJ, Lee CY (December 2003). "Cocoa has more phenolic phytochemicals and a higher antioxidant capacity than teas and red wine". J. Agric. Food Chem. 51 (25): 7292–5. doi:10.1021/jf0344385. PMID 14640573.
12.^ "Cocoa nutrient for 'lethal ills'". BBC News. http://news.bbc.co.uk/2/hi/health/.stm.
13.^ Tsushida T., Suzuki, M. (1996) Content of flavonol glucosides and some properties of enzymes metabolizing the glucosides in onion. J. Jap. Soc. Food Sci. Technol., 43, 642-649.
14.^ Slimestad R, Fossen T, Vågen IM (December 2007). "Onions: a source of unique dietary flavonoids". J. Agric. Food Chem. 55 (25): 10067–80. doi:10.1021/jf0712503. PMID 17997520.
15.^ Justesen U, Knuthsen P (2001). "Composition of flavonoids in fresh herbs and calculation of flavonoid intake by use of herbs in traditional Danish dishes". Food Chem. 73: 245–50. doi:10.1016/S0308-8146(01)00114-5.
16.^ Ewald C, Fjelkner-Modig S, Johansson K, Sjöholm I, Åkesson B (1999). "Effect of processing on major flavonoids in processed onions, green beans, and peas". Food Chem. 64: 231–5. doi:10.1016/S0308-8146(98)00136-8.
17.^ Spedding G, Ratty A, Middleton E (September 1989). "Inhibition of reverse transcriptases by flavonoids". Antiviral Res. 12 (2): 99–110. doi:10.1016/0166-3542(89)90073-9. PMID 2480745.
18.^ Kennedy JA, Matthews MA, Waterhouse AL (2002). "[Effect of Maturity and Vine Water Status on Grape Skin and Wine Flavonoids". Am. J. Enol. Vitic. 53 (4): 268–74. [http://www.ajevonline.org/cgi/content/abstract/53/4/268.
19.^ The Lancet, (December 2007). "The devil in the dark chocolate". Lancet 370 (9605): 2070. doi:10.1016/S0140-6736(07)61873-X. PMID 18156011. http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(07)61873-X.
20.^ Phenolics:figure 4
21. ^ Hwang EI, Kaneko M, Ohnishi Y, Horinouchi S (May 2003). "Production of plant-specific flavanones by Escherichia coli containing an artificial gene cluster". Appl. Environ. Microbiol. 69 (5): 2699–706. doi:10.1128/AEM.69.5.2699-2706.2003. PMID 12732539. PMC: 154558. http://aem.asm.org/cgi/pmidlookup?view=long&pmid=12732539.
22. ^ Ververidis Filippos; Trantas Emmanouil, Douglas Carl, Vollmer Guenter, Kretzschmar Georg, Panopoulos Nickolas (October 2007). "Biotechnology of flavonoids and other phenylpropanoid-derived natural products. Part II: Reconstruction of multienzyme pathways in plants and microbes". Biotechnology Journal 2 (10): 1235. doi:10.1002/biot.200700184.

External links
•Instant insight considering the effect of flavonoids on memory and learning from the Royal Society of Chemistry
•USDA Database of Flavonoid content of food (pdf)
•Flavonoids (chemistry)
•Cornell news on Cocoa
•A Dark Chocolate a Day Keeps the Doctor Away
•Antioxidant in Green Tea may fight Alzheimer's-EGCG
•Yamamoto Y, Gaynor RB (January 2001). "Therapeutic potential of inhibition of the NF-κB pathway in the treatment of inflammation and cancer". J. Clin. Invest. 107 (2): 135–42. doi:10.1172/JCI11914. PMID 11160126. PMC: 199180. http://www.jci.org/cgi/content/full/107/2/135.
•FLAVO - European Project on Flavonoid Research

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