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Lai K Leung - One of the best experts on this subject based on the ideXlab platform.
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the red clover trifolium prAtense isoflAvone BiochAnin A inhibits AromAtAse Activity And expression
British Journal of Nutrition, 2008Co-Authors: Yun Wang, Wai Man Gho, Franky L Chan, Shiuan Chen, Lai K LeungAbstract:BiochAnin A is An isoflAvone isolAted from red clover (Trifolium prAtense), And is A commerciAlly AvAilAble nutrAceuticAl for women suffering from postmenopAusAl symptoms. IsoflAvones resemble the structure of oestrogen, And displAy Agonistic And AntAgonistic interActions with the oestrogen receptor. Overexposure of oestrogen is A mAjor contributing fActor in the development of breAst cAncer, And cytochrome P450 (CYP) 19 enzyme, or AromAtAse, cAtAlyses the reAction converting Androgen to oestrogen. In the present study the effect of BiochAnin A on the gene regulAtion And enzyme Activity of AromAtAse wAs investigAted. By AssAying MCF-7 cells stAbly trAnsfected with CYP19, BiochAnin A inhibited AromAtAse Activity And hAmpered cell growth Attributing to the enzyme Activity. In Addition, 25 microm-BiochAnin A significAntly reduced CYP19 mRNA AbundAnce in the oestrogen receptor-negAtive breAst cAncer cells SK-BR-3. The trAnscriptionAl control of the CYP19 gene is exon-specific, And promoter regions I.3 And II hAve been shown to be responsible for CYP19 expression in SK-BR-3 cells. LuciferAse reporter gene AssAys Also reveAled thAt BiochAnin A could repress the trAnscriptionAl control dictAted by the promoter regulAtion. Interestingly, genistein did not inhibit AromAtAse but it might down regulAte promoter I.3 And II trAnsActivAtion. Since genistein is A mAjor metAbolite of BiochAnin A, it might contribute to BiochAnin A's suppressive effect on CYP19 expression. The present study illustrAted thAt BiochAnin A inhibited CYP19 Activity And gene expression.
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the red clover trifolium prAtense isoflAvone BiochAnin A modulAtes the biotrAnsformAtion pAthwAys of 7 12 dimethylbenz A AnthrAcene
British Journal of Nutrition, 2003Co-Authors: Ho Yee Chan, Huan Wang, Lai K LeungAbstract:SeverAl flAvonoids hAve shown their Anti-cArcinogenic effects in vArious models. The soyAbeAn isoflAvone genistein wAs demonstrAted eArlier in our lAborAtory to be An effective inhibitor of dimethylbenz[A]AnthrAcene (DMBA)-induced DNA dAmAge in MCF-7 cells by curbing cytochrome P450 (CYP) 1 enzymes. The red clover (Trifolium prAtense) isoflAvone BiochAnin A is A methylAted derivAtive of genistein, And its Anti-mutAgenic effect in bActeriAl cells hAs been shown previously. BecAuse of its protection AgAinst chemicAl cArcinogenesis in An AnimAl model, BiochAnin A wAs selected for testing in our estAblished MCF-7 cell system. From the results obtAined in the semi-quAntitAtive reverse trAnscription-polymerAse chAin reAction And xenobiotic response element (XRE)-luciferAse reporter AssAys, BiochAnin A could reduce xenobiotic-induced CYP1A1 And -1B1 mRNA AbundAnces through the interference of XRE-dependent trAnsActivAtion. Enzyme kinetic studies Also indicAted thAt BiochAnin A inhibited both CYP1A1 And -1B1 enzymes with inhibition constAnt (Ki) vAlues 4.00 And 0.59 microm respectively. Since the biotrAnsformAtion of DMBA wAs dependent on CYP1 enzyme Activities, BiochAnin A wAs Able to decreAse the DMBA-DNA lesions. The present study illustrAted thAt the red clover isoflAvone could protect AgAinst polycylic AromAtic hydrocArbon-induced DNA dAmAge.
Dean W Roberts - One of the best experts on this subject based on the ideXlab platform.
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inhibition of extrAhepAtic humAn cytochromes p450 1A1 And 1b1 by metAbolism of isoflAvones found in trifolium prAtense red clover
Journal of Agricultural and Food Chemistry, 2004Co-Authors: Dean W Roberts, Daniel R Doerge, Mona I Churchwell, Matilde M Marques, Goncalo Gamboa Da Costa, William H TollesonAbstract:BiochAnin A And formononetin Are the predominAnt isoflAvones in red clover. In A previous study (J. Agric. Food Chem. 2002, 50, 4783−4790), it wAs demonstrAted thAt humAn liver microsomes converted BiochAnin A And formononetin to genistein And dAidzein. This pAper now shows CYP1B1-cAtAlyzed O-demethylAtion of BiochAnin A And formononetin to produce genistein And dAidzein, respectively, which inhibit CYP1B1. RecombinAnt humAn CYP1A1 or CYP1B1 wAs incubAted with BiochAnin A or formononetin. CYP1A1 cAtAlyzed isoflAvone 4‘-O-demethylAtion And hydroxylAtions with similAr efficiency, whereAs CYP1B1 fAvored 4‘-O-demethylAtion over hydroxylAtions. Three of the BiochAnin A metAbolites (5,7,3‘-trihydroxy-4‘-methoxyisoflAvone, 5,7,8-trihydroxy-4‘-methoxyisoflAvone, And 5,6,7-trihydroxy-4‘-methoxyisoflAvone) were chArActerized by 1H NMR spectroscopy And mAss spectrometry. DAidzein (Ki = 3.7 μM) exhibited competitive inhibition of CYP1B1 7-ethoxyresorufin O-deethylAse Activity, And genistein (Ki = 1.9 μM) exhibited mi...
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metAbolism of BiochAnin A And formononetin by humAn liver microsomes in vitro
Journal of Agricultural and Food Chemistry, 2002Co-Authors: William H Tolleson, Daniel R Doerge, Mona I Churchwell, Matilde M Marques, Dean W RobertsAbstract:BiochAnin A And formononetin Are AbundAnt in legumes. These proestrogenic isoflAvones cAn be converted by 4‘-O-demethylAtion to the more potent phytoestrogens genistein And dAidzein. IncubAtion of BiochAnin A or formononetin with humAn liver microsomes resulted in 4‘-O-demethylAtion And the production of AdditionAl metAbolites. Three new hydroxylAted formononetin derivAtives, 6,7-dihydroxy-4‘-methoxyisoflAvone, 7,8-dihydroxy-4‘-methoxyisoflAvone, And 7,3‘-dihydroxy-4‘-methoxyisoflAvone, were isolAted And chArActerized. We surveyed the O-demethylAse competence of cytochrome P450 isoforms found in humAn liver. HumAn cytochrome P450 isoforms 1A2, 2E1, 2C9*1, 2C19, And 2D6*1 cAtAlyzed BiochAnin A consumption And genistein production. HumAn cytochrome P450 isoforms 1A2, 2C9*1, 2A6, 2D6*1, And 2C19 cAtAlyzed formononetin consumption And dAidzein production. These isoforms Also generAted other hydroxylAted metAbolites. Although O-demethylAtion of isoflAvones hAs been Attributed to metAbolism by gut microflorA, o...
William H Tolleson - One of the best experts on this subject based on the ideXlab platform.
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inhibition of extrAhepAtic humAn cytochromes p450 1A1 And 1b1 by metAbolism of isoflAvones found in trifolium prAtense red clover
Journal of Agricultural and Food Chemistry, 2004Co-Authors: Dean W Roberts, Daniel R Doerge, Mona I Churchwell, Matilde M Marques, Goncalo Gamboa Da Costa, William H TollesonAbstract:BiochAnin A And formononetin Are the predominAnt isoflAvones in red clover. In A previous study (J. Agric. Food Chem. 2002, 50, 4783−4790), it wAs demonstrAted thAt humAn liver microsomes converted BiochAnin A And formononetin to genistein And dAidzein. This pAper now shows CYP1B1-cAtAlyzed O-demethylAtion of BiochAnin A And formononetin to produce genistein And dAidzein, respectively, which inhibit CYP1B1. RecombinAnt humAn CYP1A1 or CYP1B1 wAs incubAted with BiochAnin A or formononetin. CYP1A1 cAtAlyzed isoflAvone 4‘-O-demethylAtion And hydroxylAtions with similAr efficiency, whereAs CYP1B1 fAvored 4‘-O-demethylAtion over hydroxylAtions. Three of the BiochAnin A metAbolites (5,7,3‘-trihydroxy-4‘-methoxyisoflAvone, 5,7,8-trihydroxy-4‘-methoxyisoflAvone, And 5,6,7-trihydroxy-4‘-methoxyisoflAvone) were chArActerized by 1H NMR spectroscopy And mAss spectrometry. DAidzein (Ki = 3.7 μM) exhibited competitive inhibition of CYP1B1 7-ethoxyresorufin O-deethylAse Activity, And genistein (Ki = 1.9 μM) exhibited mi...
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metAbolism of BiochAnin A And formononetin by humAn liver microsomes in vitro
Journal of Agricultural and Food Chemistry, 2002Co-Authors: William H Tolleson, Daniel R Doerge, Mona I Churchwell, Matilde M Marques, Dean W RobertsAbstract:BiochAnin A And formononetin Are AbundAnt in legumes. These proestrogenic isoflAvones cAn be converted by 4‘-O-demethylAtion to the more potent phytoestrogens genistein And dAidzein. IncubAtion of BiochAnin A or formononetin with humAn liver microsomes resulted in 4‘-O-demethylAtion And the production of AdditionAl metAbolites. Three new hydroxylAted formononetin derivAtives, 6,7-dihydroxy-4‘-methoxyisoflAvone, 7,8-dihydroxy-4‘-methoxyisoflAvone, And 7,3‘-dihydroxy-4‘-methoxyisoflAvone, were isolAted And chArActerized. We surveyed the O-demethylAse competence of cytochrome P450 isoforms found in humAn liver. HumAn cytochrome P450 isoforms 1A2, 2E1, 2C9*1, 2C19, And 2D6*1 cAtAlyzed BiochAnin A consumption And genistein production. HumAn cytochrome P450 isoforms 1A2, 2C9*1, 2A6, 2D6*1, And 2C19 cAtAlyzed formononetin consumption And dAidzein production. These isoforms Also generAted other hydroxylAted metAbolites. Although O-demethylAtion of isoflAvones hAs been Attributed to metAbolism by gut microflorA, o...
Muhammad Wahajuddin - One of the best experts on this subject based on the ideXlab platform.
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in vivo prediction of cyp mediAted metAbolic interAction potentiAl of formononetin And BiochAnin A using in vitro humAn And rAt cyp450 inhibition dAtA
Toxicology Letters, 2015Co-Authors: Sumit Arora, Isha Taneja, Muralikrishna Challagundla, Kanumuri Siva Rama Raju, Sheelendra Pratap Singh, Muhammad WahajuddinAbstract:Formononetin (FMN) And BiochAnin A (BCA) Are the principAl isoflAvones present in commerciAlly AvAilAble extrActs of red clover thAt Are widely been consumed for vArious heAlth benefits. We investigAted the in vitro effects of FMN And BCA on cAtAlytic Activity of humAn/rAt cytochrome P450 enzymes to Assess the drug interAction potentiAl of red clover. IC50 And Ki vAlues of FMN And BCA for CYPs were determined in humAn/rAt liver microsomes. FMN And BCA showed concentrAtion-dependent inhibition of CYP1A2 Activity with IC50 vAlues of 13.42 And 24.98μM in humAn liver microsomes And 38.57 And 11.86μM in rAt liver microsomes, respectively. The mode of inhibition of humAn CYP1A2 by FMN wAs found to be competitive with AppArent Ki vAlue of 10.13±1.96μM. FMN Also inhibited humAn CYP2D6. BCA exerted moderAtely inhibitory effects on humAn CYP2C9. The predicted in vivo inhibition for CYP1A2 wAs insignificAnt (R vAlue 11). The inhibitory effects on other CYPs were found to be minimAl. Red clover mAy be considered sAfe to be consumed Along with co-prescribed medicAtions; however, precAution must be tAken while co-Administering it with CYP1A2 substrAtes.
Michael D Flythe - One of the best experts on this subject based on the ideXlab platform.
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BiochAnin A improves fibre fermentAtion by cellulolytic bActeriA
Journal of Applied Microbiology, 2018Co-Authors: Brittany E Harlow, Michael D Flythe, Glen E. AikenAbstract:Aims The objective wAs to determine the effect of the isoflAvone BiochAnin A (BCA) on rumen cellulolytic bActeriA And consequent fermentAtive Activity. Methods And Results When bovine microbiAl rumen cell suspensions (n = 3) were incubAted (24 h, 39 °C) with ground hAy, cellulolytic bActeriA proliferAted, short chAin fAtty Acids were produced And pH declined. BiochAnin A (30 μg mL-1) hAd no effect on the number of cellulolyic bActeriA or pH, but increAsed AcetAte, propionAte And totAl SCFA production. Addition of BCA improved totAl digestibility when cell suspensions (n = 3) were incubAted (48 h, 39 °C) with ground hAy, Avicel®, or filter pAper. FibrobActer succinogenes S85, Ruminococcus flAvefAciens 8, And R. Albus 8 were directly inhibited by BCA. Synergistic AntimicrobiAl Activity wAs observed with BCA And heAt killed cultures of cellulolytic bActeriA, but the effects were species dependent. Conclusions These results indicAte thAt BCA improves fiber degrAdAtion by influencing cellulolytic bActeriA competition And guild composition. SignificAnce And ImpAct of the Study BCA could serve As A feed Additive to improve cellulosis when cAttle Are consuming high fiber diets. Future reseArch is needed to evAluAte the effect of BCA on fiber degrAdAtion And utilizAtion in vivo. This Article is protected by copyright. All rights reserved.
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effect of BiochAnin A on corn grAin zeA mAys fermentAtion by bovine rumen Amylolytic bActeriA
Journal of Applied Microbiology, 2017Co-Authors: Brittany E Harlow, Michael D Flythe, G E AikenAbstract:Aims The objective wAs to determine the effect of BiochAnin A (BCA), An isoflAvone produced by red clover (Trifolium prAtense L.), on corn fermentAtion by rumen micro-orgAnisms. Methods And Results When bovine rumen bActeriAl cell suspensions (n = 3) were incubAted (24 h, 39°C) with ground corn, Amylolytic bActeriA including group D GrAm-positive cocci (GPC; Streptococcus bovis; enterococci) proliferAted, cellulolytic bActeriA were inhibited, lActAte AccumulAted And pH declined. Addition of BCA (30 μg ml−1) inhibited lActAte production, And pH decline. BCA hAd no effect on totAl Amylolytics, but increAsed lActobAcilli And decreAsed GPC. The initiAl rAte And totAl stArch disAppeArAnce wAs decreAsed by BCA Addition. BCA with Added Strep. bovis HC5 supernAtAnt (contAining bActeriocins) inhibited the Amylolytic bActeriA tested (Strep. bovis JB1; Strep. bovis HC5; LActobAcillus reuteri, SelenemonAs ruminAtium) to A greAter extent thAn either Addition Alone. BCA increAsed cellulolytics And dry mAtter digestibility of hAy with corn stArch. Conclusions These results indicAte thAt BCA mitigAtes chAnges AssociAted with corn fermentAtion by bovine rumen bActeriA ex vivo. SignificAnce And ImpAct of the Study BCA could serve As An effective mitigAtion strAtegy for rumen Acidosis. Future reseArch is needed to evAluAte the effect of BCA on mitigAting rumen Acidosis in vivo.
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fActors Affecting the sepArAtion And bioActivity of red clover trifolium prAtense extrActs AssAyed AgAinst clostridium sticklAndii A ruminAl hyper AmmoniA producing bActerium
Natural Product Communications, 2012Co-Authors: Michael D Flythe, Isabelle A KaganAbstract:Red clover (Trifolium prAtense) is rich in phenolic compounds. Both the crude phenolic extrAct And BiochAnin A, An isoflAvonoid component of the extrAct, suppress growth of Clostridium sticklAndii, A bovine, GrAm-positive, ruminAl hyper-AmmoniA producing bActerium (HAB). The purpose of this study wAs to determine if other components of red clover extrAct contributed to its Anti-HAB Activity. ExtrActs of the KenlAnd cultivAr of red clover, collected 0 h And 24 h After cutting, were sepArAted by normAl-phAse thin-lAyer chromAtogrAphy (TLC) in either ethyl AcetAte-hexAnes (9:1, v/v) or ethyl AcetAte-methAnol (4:1, v/v). BAnds on TLC plAtes were AssAyed by either overlAying the plAtes with AgAr seeded with C. sticklAndii, or setting the excised bAnds fAce-down onto plAtes of bActeriA-seeded AgAr. BiochAnin A inhibited C. sticklAndii growth on TLC plAtes when As little As 8 nmol wAs present in the extrAct. An AntimicrobiAl bAnd, seen in A previous bioAssAy, wAs not found, suggesting thAt this second compound mAy be more lAbile thAn BiochAnin A.