Naringenin and some of its useful pharmakinetics - AnabolicMinds.com

Naringenin and some of its useful pharmakinetics

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    Naringenin and some of its useful pharmakinetics


    Life Sci. 2001 Jan 5;68(7):751-61. Links
    Chalcones are potent inhibitors of aromatase and 17beta-hydroxysteroid dehydrogenase activities.Le Bail JC, Pouget C, ***nere C, Basly JP, Chulia AJ, Habrioux G.
    UPRES EA 1085, Biomolecules et cibles cellulaires tumorales-Proliferation cellulaire et inhibition enzymatique Laboratoire de Biochimie, Faculte de Pharmacie, Limoges, France.

    Chalcones were tested for estimating anti-aromatase, anti-3beta-hydroxysteroid dehydrogenase delta5/delta4 isomerase (3beta-HSD) and anti-17beta-hydroxysteroid dehydrogenase (17beta-HSD) activities in human placental microsomes. In the present study, we have demonstrated for the first time that chalcones are potent inhibitors of aromatase and 17beta-hydroxysteroid dehydrogenase activities: these enzymes being considered as important targets in the metabolic pathways of human mammary hormone-dependent cells. Our results showed that naringenin chalcone and 4-hydroxychalcone were the most effective aromatase and 17beta-hydroxysteroid dehydrogenase inhibitors with IC50 values of 2.6 and 16 microM respectively. In addition, inhibitory effects of some flavones and flavanones were compared to those of the corresponding chalcones. A structure-activity relationship was established and regions or/and substituents essential for these inhibitory activities were determined.

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    Clin Pharmacol Ther. 2005 Oct;78(4):441-3.
    Effects of grapefruit juice on the pharmacokinetics of sildenafil.Jetter A, Kinzig-Schippers M, Walchner-Bonjean M, Hering U, Bulitta J, Schreiner P, Sorgel F, Fuhr U.
    Institute for Pharmacology, Clinical Pharmacology, University of Koln, Germany. alexander.jetter@medizin.uni-koeln.de

    BACKGROUND AND OBJECTIVES: Because of extensive first-pass metabolism, oral bioavailability of sildenafil reaches only 40%. Formation of the primary metabolite, N -desmethylsildenafil, is mainly mediated by the cytochrome P450 enzyme CYP3A4. In this study we investigated the influence of grapefruit juice, containing inhibitors of intestinal CYP3A4, on the pharmacokinetics of sildenafil and N -desmethylsildenafil. METHODS: In a randomized crossover study, 24 healthy white male volunteers received single 50-mg doses of sildenafil. Two doses each of 250 ml grapefruit juice or water, respectively, were administered 1 hour before and together with the drug. Plasma concentrations of sildenafil and N -desmethylsildenafil were determined up to 24 hours post dose by use of liquid chromatography-tandem mass spectrometry (limit of quantification, 1 ng/ml). RESULTS: Grapefruit juice changed the area under the sildenafil plasma concentration-time curve from time zero to infinity [AUC(0-infinity) from 620 [1.53] ng/ml x h to 761 [1.58] ng/ml x h (geometric mean with geometric standard deviation), corresponding to a 23% increase (90% confidence interval, 13%-33%). N-Desmethyl sildenafil AUC(0-infinity) increased by 24% (90% confidence interval, 17%-32%). Maximum plasma concentrations (C(max)) of sildenafil and N -desmethylsildenafil were essentially unchanged. There was a trend toward a prolonged time to reach C(max) during the grapefruit juice period (from a median of 0.75 hour to a median of 1.13 hours), corresponding to an increase by 0.25 hour (90% confidence interval, 0-0.63 hour). Interindividual variability was pronounced in both periods. CONCLUSIONS: Grapefruit juice increases sildenafil bioavailability and tends to delay sildenafil absorption. Sildenafil pharmacokinetics may become less predictable with grapefruit juice. Although patients usually will not be endangered by concomitant use of grapefruit juice, it seems advisable to avoid this combination.
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    1999 May;64(5):328-34. Links
    Xenoestrogen interaction with human sex hormone-binding globulin (hSHBG).Dechaud H, Ravard C, Claustrat F, de la Perriere AB, Pugeat M.
    Hospices Civils de Lyon, Laboratoire Central de Biochimie, France.

    This study reports on some environmental chemicals with estrogenic activity (xenoestrogens) and their binding interaction for human plasma sex-hormone binding globulin (hSHBG). The binding affinity constant of these xenoestrogens was measured in equilibrium conditions by solid phase binding assay, and their ability to displace endogenous testosterone and estradiol from hSHBG binding sites was determined with an ammonium sulfate precipitation assay in native plasma from normal men and women. The data showed that some of these xenoestrogens bind hSHBG, with a reversible and competitive binding activity for both [3H]testosterone and [3H]17beta-estradiol and with no apparent decrease in the number of hSHBG binding sites. Their respective binding affinity constants were low, ranging from 0.02 to 7.8 10(5) 1 x mol(-1). However, in native plasma from normal men and women, they were able to dose-dependently increase concentrations of hSHBG-unbound testosterone and/or estradiol. In this study, 4-nonylphenol and 4-tertoctylphenol, two alkylphenols used as surfactants in many commercial products, and bisphenol A and O-hydroxybiphenyl, widely used in the plastics industry, were identified as potent hSHBG-ligands. Additionally, the flavonoid phytoestrogens genistein and naringenin were also identified as hSHBG ligands, whereas their glucoside derivatives, genistin and naringin, had no binding activity for hSHBG. From these data, it is suggested that hSHBG binding may transport some contaminant xenoestrogens into the plasma and modulate their bioavailability to cell tissues. On the other hand, xenoestrogens may also displace endogenous sex steroid hormones from hSHBG binding sites and disrupt the androgen-to-estrogen balance. Whether xenoestrogen SHBG ligands could reach high enough concentrations in the blood to expose humans to any such effect merits further investigation.
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    Reprod Nutr Dev. 2005 Nov-Dec;45(6):709-20. Links
    The effects of dietary phytoestrogens on aromatase activity in human endometrial stromal cells.Edmunds KM, Holloway AC, Crankshaw DJ, Agarwal SK, Foster WG.
    Reproductive Biology Division, Department of Obstetrics and Gynecology, McMaster University, Hamilton, Ontario.

    Dietary phytoestrogens have been reported to inhibit aromatase activity in placental microsomes, but the effects in the human endometrium are unknown. Aromatase, the rate-limiting enzyme in the conversion of androgens to estrogens, has recently been shown to be expressed in the endometrium of women with endometriosis and is thought to play a role in the pathophysiology of this disease. Therefore, the objective of this study was to screen dietary phytoestrogens for their ability to inhibit aromatase activity in human endometrial stromal cells (ESC) and identify potential novel therapeutic agents for the treatment of endometriosis. The inhibition of aromatase activity by direct interaction with the dietary phytoestrogens genistein, daidzein, chrysin, and naringenin was tested in a cell free assay. Furthermore, test compound effects on aromatase activity in ESC cultures were also examined. Genistein and daidzein were inactive in the human recombinant aromatase assay whereas naringenin and chrysin inhibited aromatase activity. However, genistein (1 nM to 1 mM) stimulated aromatase activity in ESC whereas other phytoestrogens had no effect. Immunopositive aromatase cells were demonstrated in genistein-treated ESC but not in untreated control cultures. Taken together, our data suggest that genistein can increase aromatase activity in ESC likely via increased enzyme expression.
  5. Vitruvian's Avatar
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    D,

    Can we get a translation on the Sildenafil article? Please and thank you.
    Applied Nutriceuticals Representative
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  6. Outside Backer's Avatar
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    i read thru some of this. I eat the hell out of grapefruits. Doensnt the Narin... also extend the effects of caffiene on metabolism. and also lowers hunger pains to correct?


    tap a bit of splenda on some Grapefruit and you got a great snack
    toes-on-the-nose.blogspot.com Deployed blogging
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    Quote Originally Posted by Outside Backer View Post
    i read thru some of this. I eat the hell out of grapefruits. Doensnt the Narin... also extend the effects of caffiene on metabolism. and also lowers hunger pains to correct?


    tap a bit of splenda on some Grapefruit and you got a great snack
    Grapefruit is the bomb with some splenda!
    I used it HEAVILY in contest prep. I was using a Beverly diet.... interestingly: they had me eating grapefruit and lean ground beef only, for a couple days pre-contest.
    Applied Nutriceuticals Representative
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    Quote Originally Posted by Outside Backer View Post
    i read thru some of this. I eat the hell out of grapefruits. Doensnt the Narin... also extend the effects of caffiene on metabolism. and also lowers hunger pains to correct?


    tap a bit of splenda on some Grapefruit and you got a great snack
    si senor Extends the life of caffeine in the body, along with most other medications
  9. rms80's Avatar
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    Quote Originally Posted by rms80 View Post
    Clin Pharmacol Ther. 2005 Oct;78(4):441-3.
    Effects of grapefruit juice on the pharmacokinetics of sildenafil.Jetter A, Kinzig-Schippers M, Walchner-Bonjean M, Hering U, Bulitta J, Schreiner P, Sorgel F, Fuhr U.
    Institute for Pharmacology, Clinical Pharmacology, University of Koln, Germany. alexander.jetter@medizin.uni-koeln.de

    BACKGROUND AND OBJECTIVES: Because of extensive first-pass metabolism, oral bioavailability of sildenafil reaches only 40%. Formation of the primary metabolite, N -desmethylsildenafil, is mainly mediated by the cytochrome P450 enzyme CYP3A4. In this study we investigated the influence of grapefruit juice, containing inhibitors of intestinal CYP3A4, on the pharmacokinetics of sildenafil and N -desmethylsildenafil. METHODS: In a randomized crossover study, 24 healthy white male volunteers received single 50-mg doses of sildenafil. Two doses each of 250 ml grapefruit juice or water, respectively, were administered 1 hour before and together with the drug. Plasma concentrations of sildenafil and N -desmethylsildenafil were determined up to 24 hours post dose by use of liquid chromatography-tandem mass spectrometry (limit of quantification, 1 ng/ml). RESULTS: Grapefruit juice changed the area under the sildenafil plasma concentration-time curve from time zero to infinity [AUC(0-infinity) from 620 [1.53] ng/ml x h to 761 [1.58] ng/ml x h (geometric mean with geometric standard deviation), corresponding to a 23% increase (90% confidence interval, 13%-33%). N-Desmethyl sildenafil AUC(0-infinity) increased by 24% (90% confidence interval, 17%-32%). Maximum plasma concentrations (C(max)) of sildenafil and N -desmethylsildenafil were essentially unchanged. There was a trend toward a prolonged time to reach C(max) during the grapefruit juice period (from a median of 0.75 hour to a median of 1.13 hours), corresponding to an increase by 0.25 hour (90% confidence interval, 0-0.63 hour). Interindividual variability was pronounced in both periods. CONCLUSIONS: Grapefruit juice increases sildenafil bioavailability and tends to delay sildenafil absorption. Sildenafil pharmacokinetics may become less predictable with grapefruit juice. Although patients usually will not be endangered by concomitant use of grapefruit juice, it seems advisable to avoid this combination.
    Sure- article basically states that grapefruit juice (and its constituent compounds naringin and naringenin) can increase the bioavailiability of PDE4 and 5 inhibitors such as slidenafil (viagra) by 23-24%. Grape fruit juice can also delay the absorption as well, almost like a time-release
  10. Outside Backer's Avatar
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    i wonder if grapefruit can extend pct liquids nolva.......
    toes-on-the-nose.blogspot.com Deployed blogging
  11. Vitruvian's Avatar
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    The plot thickens.....
    Applied Nutriceuticals Representative
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  12. stxnas's Avatar
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    (Subscribed) Thanks for the posts...and the translations, lol.
    RcB Since 09-06-2011 20:55 EST, Post 49
  13. buffhunk29's Avatar
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    Great write up!

    Thats why us bodybuilder know what to eat there is a method to the carzy eatting habits bodybuilders and it just goes to show you how important food really is!!

    I think Backer just called up sams club and ordered a whole shipment of grapefruit for himself you selfish!! haha
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    Quote Originally Posted by Outside Backer View Post
    i wonder if grapefruit can extend post cycle therapy liquids nolva.......
    It should- in the following study, quercetin enhances the bioavaliability of tamoxifen. Quercetin does this by inhibiting CYP3A4, the same thing naringin and naringenin do- so yes, probably

    Int J Pharm. 2006 Apr 26;313(1-2):144-9. Epub 2006 Mar 3. Links
    Enhanced bioavailability of tamoxifen after oral administration of tamoxifen with quercetin in rats.Shin SC, Choi JS, Li X.
    College of Pharmacy, Chonnam National University, Bukgu, Gwangju 500-757, Republic of Korea.

    Orally administered tamoxifen undergoes a first-pass metabolism and substrates for multidrug resistance (MDR) transporters efflux in the liver and intestines, which obstructs its systemic exposure. This study investigated the effect of quercetin, a dual inhibitor of CYP3A4 and P-gp, on the bioavailability and pharmacokinetics of tamoxifen and one of its metabolites, 4-hydroxytamoxifen, in rats. The pharmacokinetic parameters of tamoxifen and 4-hydroxytamoxifen in plasma were determined after orally administering tamoxifen (10 mg/kg) with or without quercetin (2.5, 7.5 and 15 mg/kg). The coadministration of quercetin (2.5 and 7.5 mg/kg) significantly (p < 0.05) increased the absorption rate constant (K(a)), peak concentration (C(max)) and the areas under the plasma concentration-time curve (AUC) of tamoxifen. The absolute bioavailability (AB%) of tamoxifen with 2.5 and 7.5 mg/kg quercetin ranged from 18.0% to 24.1%, which was significantly higher than the control group, 15.0% (p < 0.05). The relative bioavailability (RB%) of tamoxifen coadministered with quercetin was 1.20-1.61 times higher than the control group. The coadministration of quercetin caused no significant changes in the terminal half-life (t(1/2)) and the time to reach the peak concentration (T(max)) of tamoxifen. Compared with the control group, the coadministration of 7.5 mg/kg quercetin significantly (p < 0.05) increased the AUC of 4-hydroxytamoxifen. However, the metabolite ratios (MR; AUC of 4-hydroxytamoxifen to tamoxifen) were significantly lower (p < 0.05). This suggests that quercetin inhibits the both MDR transporters efflux and first-pass metabolism of tamoxifen. The enhanced bioavailability of tamoxifen as a result of its coadministration with quercetin might be due to the effect of quercetin promoting the intestinal absorption and reducing the first-pass metabolism of tamoxifen. If the results are further confirmed in the clinical trials, the tamoxifen dosage should be adjusted when tamoxifen is administered with quercetin or quercetin-containing dietary supplements in order to avoid potential drug interactions.
  15. Vitruvian's Avatar
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    You got mail, D $
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    Quote Originally Posted by Lanbane View Post
    You got mail, D $
    Back at ya- tried to explain it as best I could
  17. Outside Backer's Avatar
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    ahhh good news to see.

    shipment of grapfruit should be here lol
    toes-on-the-nose.blogspot.com Deployed blogging
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    Quote Originally Posted by Outside Backer View Post
    ahhh good news to see.

    shipment of grapfruit should be here lol
    Good stuff- I drink grapefruit juice every morning
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    HAHA Backer will you share? They told me they wont get another shipment for a month you bought so much! LOL
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    this may have already been covered -

    but was wondering about:

    Naringenin + Methly Designer Steroid/Prohormone = GOOD/BAD?

    in theory, shouldn't it allow you to take less hormone and get the same results? or would it help exagerate the negative sides?
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    never mind -

    found the answer on another thread: RPM on Cycle??
  22. rms80's Avatar
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    Quote Originally Posted by Hank Vangut View Post
    never mind -

    found the answer on another thread: RPM on Cycle??
    No worries!!
    Dirk Tanis, BA, MSci
    Chief Operating Officer, Applied Nutriceuticals
  

  
 

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