FLAVONOIDS/POLYPHENOLS

Flavonoids are polyphenolic compounds that are ubiquitous in nature and are categorized, according to chemical structure, into flavonols, flavones, flavanones, isoflavones, catechins, anthocyanidins and chalcones. Over 4,000 flavonoids have beenidentified,manyofwhichoccurinfruits,vegetablesandbeverages(tea,coffee, beer, wine and fruit drinks). The flavonoids have aroused considerable interest recentlybecauseoftheirpotentialbeneficialeffectsonhumanhealththeyhavebeen reported to have antiviral, antiallergic, antiplatelet, antiinflammatory, antitumor andantioxidantactivities. Antioxidants are compounds that protect cells against the damaging effects of reactive oxygen species, such as singlet oxygen, superoxide, peroxyl radicals, hydroxylradicalsandperoxynitrite.Animbalancebetweenantioxidantsandreactive oxygen species results in oxidative stress, leading to cellular damage. Oxidative stress has been linked to cancer, aging, atherosclerosis, ischemic injury, inflammation and neurodegenerative diseases (Parkinson's and Alzheimer's). Flavonoidsmayhelpprovideprotectionagainstthesediseasesbycontributing,along with antioxidant vitamins and enzymes, to the total antioxidant defense system of the human body. Epidemiological studies have shown that flavonoid intake is inversely related to mortality from coronary heart disease and to the incidence of heartattacks. The recognized dietary antioxidants are vitamin C, vitamin E, selenium, and carotenoids. However, recent studies have demonstrated that flavonoids found in fruitsandvegetablesmayalsoactasantioxidants.Likealphatocopherol(vitaminE), flavonoids contain chemical structural elements that may be responsible for their antioxidant activities. The contribution of flavonoids to the antioxidant defense system may be substantial considering that the total daily intake of flavonoids can rangefrom50to800mg.Thisintakeishighcomparedtotheaveragedailyintakeof other dietary antioxidants like vitamin C (70 mg), vitamin E (710 mg) or carotenoids (23 mg). Flavonoid intake depends upon the consumption of fruits, vegetables, and certain beverages, such as red wine, tea, and beer. The high consumption of tea and wine may be most influential on total flavonoid intake in certaingroupsofpeople. Antioxidantflavonoids (listedinorderofdecreasingpotency) Quercetin(aflavonolinvegetables,fruitskins,onions) Xanthohumol(aprenylatedchalconeinhopsandbeer) Isoxanthohumol (a prenylated flavanone in hops and beer) Genistein(anisoflavoneinsoy)

Prooxidantflavonoids Chalconaringenin (a nonprenylated chalcone in citrus fruits) Naringenin(anonprenylatedflavanoneincitrusfruits)

The capacity of flavonoids to act as antioxidants depends upon their molecular structure. The position of hydroxyl groups and other features in the chemical structureofflavonoidsareimportantfortheirantioxidantandfreeradicalscavenging activities. Quercetin, the most abundant dietary flavonol, is a potent antioxidant becauseithasalltherightstructuralfeaturesforfreeradicalscavengingactivity. Recently,chalconeandflavanone flavonoidswithprenylorgeranylsidechainshave beenidentifiedinhopsandbeerbyDr.FredStevensandDr.MaxDeinzeratOregon State University. Hops are used in beer for flavor. Xanthohumol (a chalcone) and isoxanthohumoland6prenylnaringenin(flavanones)arethemajorprenylflavonoids foundinbeer.Althoughtheantioxidantactivitiesofthesecompoundshavenotbeen studied, these flavonoids may be responsible for the antioxidant activity of lager beer, which is higher than that of green tea, red wine, or grape juice as reported earlier by Dr. Joe A. Vinson from the University of Scranton in Pennsylvania. Xanthohumolisfoundonlyinbeerbutinsmallconcentrations. Toassesstheantioxidantactivityoftheprenylatedflavonoids,Dr.DonaldBuhlerand Dr. Cristobal Mirand (The Linus Pauling Institute, Oregan, USA) evaluated the capacityoftheseflavonoidstoinhibittheoxidationofLDLbycopper.Theantioxidant propertiesoftheprenylflavonoidswerecomparedtothoseofquercetin(aflavonol), genistein (the major isoflavone in soy), chalconaringenin (a nonprenylated chalcone), naringenin (a nonprenylated flavanone), and vitamin E. The possible interaction of xanthohumol, the major prenylchalcone in beer, with vitamin E to inhibit LDL oxidation induced by copper was also examined.Their results showed that the prenylchalcones and prenylflavones are effective in preventing LDL oxidationinitiated by copper and that the prenylchalcones generally have greater antioxidant activity than the prenylflavanones. Xanthohumol, the major prenylchalconein hopsand beer,is a morepowerful antioxidantthanvitaminEor genistein. However, xanthohumol was less potent than quercetin. The potency of xanthohumol as an antioxidant is markedly increased when combined with an equivalentamountofvitaminE. Dr. Buhlers team also found that the prenyl group plays an important role in the antioxidantactivityofcertainflavonoids.Aflavonoidchalcone(chalconaringenin)and a flavanone (naringenin) with no prenyl groups act as prooxidants, i.e. they promoterather thanlimittheoxidationofLDLbycopper.However,addingaprenyl grouptotheseflavonoidmoleculescounteractedtheirprooxidantactivities. Recentworksshowedthatthereareuniqueflavonoidsinhopsandbeerthatmaybe potentially useful in the preventionof human disease attributed to free radical damage.Theobservationthatprenylgroupsareimportantinconferringantioxidant activity to certain flavonoids may lead to the discovery or synthesis of novel prenylated flavonoids as preventive or therapeutic agents against human diseases associated with free radicals. Recent results with xanthohumol suggest that this

prenylchalcone should be further studied for its antioxidant action and protective effectsagainstfreeradicaldamageinanimalsandhumans.Preliminarystudieshave shown that xanthohumol is absorbed from the digestive tract in rats, and more studies are needed to evaluate the bioavailability of these interesting flavonoids in people. Further studies are also needed to establish the safety of xanthohumol or other flavonoidsforuseasdietarysupplementssincehighdosesofthesecompoundsmay produce adverse effects in humans, according to recent findings by Dr. Martyn Smith,professoroftoxicology,UniversityofCaliforniaatBerkeley.