N Demethylase

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Julio Benitez - One of the best experts on this subject based on the ideXlab platform.

  • caffeiNe Demethylase activity iN humaN aNd dark agouti rat liver microsomes comparisoN with amiNopyriNe N Demethylase activity
    Drug Metabolism and Disposition, 1992
    Co-Authors: Jose A G Agundez, Antonio Luengo, Julio Benitez
    Abstract:

    HumaN aNd Dark Agouti rat liver microsomes were aNalyzed for caffeiNe metabolism focusiNg oN Demethylase activity by usiNg a simplified isocratic HPLC method. Results showed that, despite iNterspecies quaNtitative aNd qualitative differeNces oN caffeiNe metabolism, maiNly demethylated caffeiNe metabolites were detected iN both species. HumaNs showed iNteriNdividual quaNtitative differeNces iN caffeiNe Demethylase activity iN coNtrast to rats aNd, iN both cases, the proportioN of metabolites remaiNed coNstaNt. IN additioN, amiNopyriNe N-Demethylase activity was assayed, showiNg a direct correlatioN with caffeiNe Demethylase activity iN humaNs (r = 0.71) that is reported here for the first time, but Not iN rats (r = 0.21). These results iNdicate that, iN humaN liver microsomes, caffeiNe aNd amiNopyriNe could be demethylated by the same or by closely related eNzymes; whereas iN Dark Agouti rats, there is No appareNt relatioN betweeN caffeiNe aNd amiNopyriNe demethylatioN pathways.

  • sex aNd age related differeNces iN amiNopyriNe N Demethylase activity iN da aNd wistar straiN rat liver microsomes effect of ovariectomy
    Xenobiotica, 1991
    Co-Authors: Jose Augusto Garciaagundez, Julio Benitez
    Abstract:

    1. Liver microsomal mixed-fuNctioN oxidase compoNeNts were studied iN Wistar aNd Dark Agouti (DA) rats (4-45 weeks) with regard to sex- aNd age-related differeNces. Total cytochrome P-450 raNged from 0.29 to 1 Nmol/mg iN Wistar rats aNd from 0.21 to 1.27 Nmol/mg iN DA rats, males had higher levels thaN females (P<0.0025). Cytochrome b5 raNged betweeN 0.42-1.37 Nmol/mg aNd 0.42-1.56 Nmol/mg iN Wistar aNd DA straiNs, respectively, aNd NADPH-reductase activity raNged betweeN 14-43 aNd 11-46 Nmol/miN per mg (Wistar aNd DA respectively).2. SigNificaNt age-related differeNces were fouNd iN DA rats with four- to six-fold iNcrease iN N-Demethylase activity from youNg to adult rats. Sex-related differeNces were fouNd iN both Wistar- aNd DA-straiN rats, with males haviNg higher (about twice) metabolic activity thaN females. IN coNtrast, No sigNificaNt sex- or age-related differeNces iN cytochrome 5 coNteNt, or NADPH-reductase activity, were fouNd.3. Ovariectomy of 10-13-week-old females did Not affect N-Demethylase...

  • amiNopyriNe N Demethylase activity iN humaN liver microsomes
    Clinical Pharmacology & Therapeutics, 1990
    Co-Authors: Jose Augusto Garciaagundez, Antonio Luengo, Julio Benitez
    Abstract:

    AmiNopyriNe N-Demethylase activity aNd the coNteNts of cytochrome P-450, cytochrome b5, aNd NADPH-reductase activity iN humaN liver microsomes from 31 differeNt patieNts were studied. Our results show the existeNce of sigNificaNt iNteriNdividual, but Not sex- or age-related differeNces N-Demethylase activity (raNgiNg betweeN 0.52 aNd 4.42 Nmol/miN/mg proteiN), aNd that these differeNces are directly correlated with the coNteNt of cytochrome P-450 aNd NADPH-reductase activity, but Not with that of cytochrome b5 coNteNt, iN the samples. IN coNtrast, No differeNces were fouNd iN the Michaelis-MeNteN coNstaNt values for amiNopyriNe (meaN, 2.4 mmol/L) or NADPH (meaN, 69 μmol/L), stroNgly suggestiNg that iNteriNdividual differeNces could be due to the occurreNce of differeNt amouNts of the same eNzyme, rather thaN the preseNce of differeNt eNzymes, iN the populatioN studied. CliNical Pharmacology aNd Therapeutics (1990) 48, 490–495; doi:10.1038/clpt.1990.184

  • AmiNopyriNe NDemethylase activity iN humaN liver microsomes
    Clinical Pharmacology & Therapeutics, 1990
    Co-Authors: Jose Augusto García-agúndez, Antonio Luengo, Julio Benitez
    Abstract:

    AmiNopyriNe N-Demethylase activity aNd the coNteNts of cytochrome P-450, cytochrome b5, aNd NADPH-reductase activity iN humaN liver microsomes from 31 differeNt patieNts were studied. Our results show the existeNce of sigNificaNt iNteriNdividual, but Not sex- or age-related differeNces N-Demethylase activity (raNgiNg betweeN 0.52 aNd 4.42 Nmol/miN/mg proteiN), aNd that these differeNces are directly correlated with the coNteNt of cytochrome P-450 aNd NADPH-reductase activity, but Not with that of cytochrome b5 coNteNt, iN the samples. IN coNtrast, No differeNces were fouNd iN the Michaelis-MeNteN coNstaNt values for amiNopyriNe (meaN, 2.4 mmol/L) or NADPH (meaN, 69 μmol/L), stroNgly suggestiNg that iNteriNdividual differeNces could be due to the occurreNce of differeNt amouNts of the same eNzyme, rather thaN the preseNce of differeNt eNzymes, iN the populatioN studied. CliNical Pharmacology aNd Therapeutics (1990) 48, 490–495; doi:10.1038/clpt.1990.184

Sharif Mahsufi Mansor - One of the best experts on this subject based on the ideXlab platform.

  • IN vitro effect of mitragyNiNe oN activity of drug metaboliziNg eNzymes, N-Demethylase aNd glutathioNe s-traNsferase iN streptozotociN-iNduced diabetic rats
    2020
    Co-Authors: Rukhsana Anwar, Abas Hj Hussin, Sabariah Ismail, Sharif Mahsufi Mansor
    Abstract:

    MitragyNiNe is the major alkaloid of MitragyNa speciosa Korth. It is respoNsible for aNtiNociceptive, aNtidepressaNt like effects aNd used as substitute for morphiNe to treat opium withdrawal. MitragyNa speciosa plaNt beloNgs to Rubiaceae family. IN Malaysia, the leaves of MitragyNa speciosa are used to treat diarrhea, paiN aNd as cough suppressaNt. FollowiNg experimeNts were uNdertakeN to evaluate the effect of mitragyNiNe oN amiNopyriNe N-Demethylase aNd glutathioNe S-traNsferase activity iN diabetic Sprague-Dawley (SD) male aNd female rats. DiffereNt coNceNtratioNs of mitragyNiNe (0.0025µM-250µM) were used to evaluate activity of both eNzymes. CollageNase perfusioN techNique was used to isolate hepatocytes aNd amiNopyriNe NDemethylase activity was determiNed iN hepatocytes by measuriNg the quaNtity of formaldehyde formed. Rat livers were takeN out aNd cytosolic fractioN was prepared. GST activity was measured iN cytosolic fractioN by kiNetics of thioether product formatioN over time. Results showed that iN diabetic male aNd female SD rat hepatocytes, a sigNificaNt (p< 0.05) iNcrease iN amiNopyriNe N-Demethylase activity was observed oNly with 250µM mitragyNiNe. For phase II drug metaboliziNg eNzyme, mitragyNiNe (0.25µM -250µM) sigNificaNtly (p

  • MitragyNa speciosa Korth leaves extracts iNduced the CYP450 catalyzed amiNopyriNe-N-Demethylase (APND) aNd UDP-glucuroNosyl traNsferase (UGT) activities iN male Sprague-Dawley rat livers.
    Drug metabolism and drug interactions, 2013
    Co-Authors: Juzaili Azizi, Sabariah Ismail, Sharif Mahsufi Mansor
    Abstract:

    BACKGROUND: MitragyNa speciosa leaves have beeN abused by drug addicts as some of the alkaloids (maiNly mitragyNiNe) from the plaNt possess opiate aNd cocaiNe-like effects. These briNg to its prohibitioN iN Malaysia iN 2004 as coNsumptioN of M. speciosa leaves has beeN perceived to lead to the abuse of other drugs such as caNNabis aNd heroiN. METHODS: IN the curreNt study, the iN vitro aNd iN vivo effects of M. speciosa methaNolic, aqueous aNd total alkaloid leaves extracts oN drug metaboliziNg eNzymes, Namely, cytochrome P450s (CYP450s) aNd UDP-glucuroNosyl traNsferase (UGT) had beeN evaluated iN rat liver cytosolic fractioN aNd microsomes. AmiNopyriNe aNd p-NitropheNol (pNP) were employed as probe substrates iN amiNopyriNe N-Demethylase (APND) aNd UGT eNzyme assays, respectively. Furthermore, mitragyNiNe was also tested iN vitro for its likelihood to iNhibit APND aNd UGT activity. The assessmeNt of the eNzyme activity was coNducted usiNg spectrophotometric methods. RESULTS: IN vitro, the IC50 value could oNly be obtaiNed for the methaNolic extract iN APND study (595.30±30.78 µg/mL) aNd Not iN other studies due to the eNzyme perceNtage iNhibitioNs beiNg

  • mitragyNa speciosa korth leaves extracts iNduced the cyp450 catalyzed amiNopyriNe N Demethylase apNd aNd udp glucuroNosyl traNsferase ugt activities iN male sprague dawley rat livers
    Drug metabolism and drug interactions, 2013
    Co-Authors: Juzaili Azizi, Sabariah Ismail, Sharif Mahsufi Mansor
    Abstract:

    BACKGROUND: MitragyNa speciosa leaves have beeN abused by drug addicts as some of the alkaloids (maiNly mitragyNiNe) from the plaNt possess opiate aNd cocaiNe-like effects. These briNg to its prohibitioN iN Malaysia iN 2004 as coNsumptioN of M. speciosa leaves has beeN perceived to lead to the abuse of other drugs such as caNNabis aNd heroiN. METHODS: IN the curreNt study, the iN vitro aNd iN vivo effects of M. speciosa methaNolic, aqueous aNd total alkaloid leaves extracts oN drug metaboliziNg eNzymes, Namely, cytochrome P450s (CYP450s) aNd UDP-glucuroNosyl traNsferase (UGT) had beeN evaluated iN rat liver cytosolic fractioN aNd microsomes. AmiNopyriNe aNd p-NitropheNol (pNP) were employed as probe substrates iN amiNopyriNe N-Demethylase (APND) aNd UGT eNzyme assays, respectively. Furthermore, mitragyNiNe was also tested iN vitro for its likelihood to iNhibit APND aNd UGT activity. The assessmeNt of the eNzyme activity was coNducted usiNg spectrophotometric methods. RESULTS: IN vitro, the IC50 value could oNly be obtaiNed for the methaNolic extract iN APND study (595.30±30.78 µg/mL) aNd Not iN other studies due to the eNzyme perceNtage iNhibitioNs beiNg <70%. IN coNtrast to the iN vitro study, the oral treatmeNt of male Sprague-Dawley rats for 14 days with 50, 100 aNd 200 mg/kg of methaNolic aNd aqueous extracts aNd with 5, 10 aNd 20 mg/kg of total alkaloid extract showed a profouNd iNcremeNt oN the APND aNd UGT activities. CONCLUSIONS: The curreNt fiNdiNgs showed that possibilities exist for herb-drug iNteractioN with iNcreased clearaNce of drugs, which are primarily metabolized by CYP450s aNd UGT1A6 amoNg M. speciosa leaves extract users.

  • iN vitro effect of mitragyNiNe oN activity of drug metaboliziNg eNzymes N Demethylase aNd glutathioNe s traNsferase iN streptozotociN iNduced diabetic rats
    2012
    Co-Authors: Rukhsana Anwar, Abas Hj Hussin, Sabariah Ismail, Sharif Mahsufi Mansor
    Abstract:

    MitragyNiNe is the major alkaloid of MitragyNa speciosa Korth. It is respoNsible for aNtiNociceptive, aNtidepressaNt like effects aNd used as substitute for morphiNe to treat opium withdrawal. MitragyNa speciosa plaNt beloNgs to Rubiaceae family. IN Malaysia, the leaves of MitragyNa speciosa are used to treat diarrhea, paiN aNd as cough suppressaNt. FollowiNg experimeNts were uNdertakeN to evaluate the effect of mitragyNiNe oN amiNopyriNe N-Demethylase aNd glutathioNe S-traNsferase activity iN diabetic Sprague-Dawley (SD) male aNd female rats. DiffereNt coNceNtratioNs of mitragyNiNe (0.0025µM-250µM) were used to evaluate activity of both eNzymes. CollageNase perfusioN techNique was used to isolate hepatocytes aNd amiNopyriNe NDemethylase activity was determiNed iN hepatocytes by measuriNg the quaNtity of formaldehyde formed. Rat livers were takeN out aNd cytosolic fractioN was prepared. GST activity was measured iN cytosolic fractioN by kiNetics of thioether product formatioN over time. Results showed that iN diabetic male aNd female SD rat hepatocytes, a sigNificaNt (p< 0.05) iNcrease iN amiNopyriNe N-Demethylase activity was observed oNly with 250µM mitragyNiNe. For phase II drug metaboliziNg eNzyme, mitragyNiNe (0.25µM -250µM) sigNificaNtly (p<0.05) iNhibited the GST specific activity iN both diabetic male aNd female rats. IN coNclusioN this study iNdicates that the amiNopyriNe N-Demethylase eNzyme iNductioN aNd GST activity iNhibitioN by mitragyNiNe is Not iNflueNced by sex. AmiNopyriNe N-Demethylase activity iNcreases oNly oN high coNceNtratioN of mitragyNiNe aNd lower coNceNtratioNs caNNot be able to chaNge it. However GST activity iNhibitioN is dosedepeNdeNt.

Jose Augusto Garciaagundez - One of the best experts on this subject based on the ideXlab platform.

  • sex aNd age related differeNces iN amiNopyriNe N Demethylase activity iN da aNd wistar straiN rat liver microsomes effect of ovariectomy
    Xenobiotica, 1991
    Co-Authors: Jose Augusto Garciaagundez, Julio Benitez
    Abstract:

    1. Liver microsomal mixed-fuNctioN oxidase compoNeNts were studied iN Wistar aNd Dark Agouti (DA) rats (4-45 weeks) with regard to sex- aNd age-related differeNces. Total cytochrome P-450 raNged from 0.29 to 1 Nmol/mg iN Wistar rats aNd from 0.21 to 1.27 Nmol/mg iN DA rats, males had higher levels thaN females (P<0.0025). Cytochrome b5 raNged betweeN 0.42-1.37 Nmol/mg aNd 0.42-1.56 Nmol/mg iN Wistar aNd DA straiNs, respectively, aNd NADPH-reductase activity raNged betweeN 14-43 aNd 11-46 Nmol/miN per mg (Wistar aNd DA respectively).2. SigNificaNt age-related differeNces were fouNd iN DA rats with four- to six-fold iNcrease iN N-Demethylase activity from youNg to adult rats. Sex-related differeNces were fouNd iN both Wistar- aNd DA-straiN rats, with males haviNg higher (about twice) metabolic activity thaN females. IN coNtrast, No sigNificaNt sex- or age-related differeNces iN cytochrome 5 coNteNt, or NADPH-reductase activity, were fouNd.3. Ovariectomy of 10-13-week-old females did Not affect N-Demethylase...

  • amiNopyriNe N Demethylase activity iN humaN liver microsomes
    Clinical Pharmacology & Therapeutics, 1990
    Co-Authors: Jose Augusto Garciaagundez, Antonio Luengo, Julio Benitez
    Abstract:

    AmiNopyriNe N-Demethylase activity aNd the coNteNts of cytochrome P-450, cytochrome b5, aNd NADPH-reductase activity iN humaN liver microsomes from 31 differeNt patieNts were studied. Our results show the existeNce of sigNificaNt iNteriNdividual, but Not sex- or age-related differeNces N-Demethylase activity (raNgiNg betweeN 0.52 aNd 4.42 Nmol/miN/mg proteiN), aNd that these differeNces are directly correlated with the coNteNt of cytochrome P-450 aNd NADPH-reductase activity, but Not with that of cytochrome b5 coNteNt, iN the samples. IN coNtrast, No differeNces were fouNd iN the Michaelis-MeNteN coNstaNt values for amiNopyriNe (meaN, 2.4 mmol/L) or NADPH (meaN, 69 μmol/L), stroNgly suggestiNg that iNteriNdividual differeNces could be due to the occurreNce of differeNt amouNts of the same eNzyme, rather thaN the preseNce of differeNt eNzymes, iN the populatioN studied. CliNical Pharmacology aNd Therapeutics (1990) 48, 490–495; doi:10.1038/clpt.1990.184

Sabariah Ismail - One of the best experts on this subject based on the ideXlab platform.

  • IN vitro effect of mitragyNiNe oN activity of drug metaboliziNg eNzymes, N-Demethylase aNd glutathioNe s-traNsferase iN streptozotociN-iNduced diabetic rats
    2020
    Co-Authors: Rukhsana Anwar, Abas Hj Hussin, Sabariah Ismail, Sharif Mahsufi Mansor
    Abstract:

    MitragyNiNe is the major alkaloid of MitragyNa speciosa Korth. It is respoNsible for aNtiNociceptive, aNtidepressaNt like effects aNd used as substitute for morphiNe to treat opium withdrawal. MitragyNa speciosa plaNt beloNgs to Rubiaceae family. IN Malaysia, the leaves of MitragyNa speciosa are used to treat diarrhea, paiN aNd as cough suppressaNt. FollowiNg experimeNts were uNdertakeN to evaluate the effect of mitragyNiNe oN amiNopyriNe N-Demethylase aNd glutathioNe S-traNsferase activity iN diabetic Sprague-Dawley (SD) male aNd female rats. DiffereNt coNceNtratioNs of mitragyNiNe (0.0025µM-250µM) were used to evaluate activity of both eNzymes. CollageNase perfusioN techNique was used to isolate hepatocytes aNd amiNopyriNe NDemethylase activity was determiNed iN hepatocytes by measuriNg the quaNtity of formaldehyde formed. Rat livers were takeN out aNd cytosolic fractioN was prepared. GST activity was measured iN cytosolic fractioN by kiNetics of thioether product formatioN over time. Results showed that iN diabetic male aNd female SD rat hepatocytes, a sigNificaNt (p< 0.05) iNcrease iN amiNopyriNe N-Demethylase activity was observed oNly with 250µM mitragyNiNe. For phase II drug metaboliziNg eNzyme, mitragyNiNe (0.25µM -250µM) sigNificaNtly (p

  • MitragyNa speciosa Korth leaves extracts iNduced the CYP450 catalyzed amiNopyriNe-N-Demethylase (APND) aNd UDP-glucuroNosyl traNsferase (UGT) activities iN male Sprague-Dawley rat livers.
    Drug metabolism and drug interactions, 2013
    Co-Authors: Juzaili Azizi, Sabariah Ismail, Sharif Mahsufi Mansor
    Abstract:

    BACKGROUND: MitragyNa speciosa leaves have beeN abused by drug addicts as some of the alkaloids (maiNly mitragyNiNe) from the plaNt possess opiate aNd cocaiNe-like effects. These briNg to its prohibitioN iN Malaysia iN 2004 as coNsumptioN of M. speciosa leaves has beeN perceived to lead to the abuse of other drugs such as caNNabis aNd heroiN. METHODS: IN the curreNt study, the iN vitro aNd iN vivo effects of M. speciosa methaNolic, aqueous aNd total alkaloid leaves extracts oN drug metaboliziNg eNzymes, Namely, cytochrome P450s (CYP450s) aNd UDP-glucuroNosyl traNsferase (UGT) had beeN evaluated iN rat liver cytosolic fractioN aNd microsomes. AmiNopyriNe aNd p-NitropheNol (pNP) were employed as probe substrates iN amiNopyriNe N-Demethylase (APND) aNd UGT eNzyme assays, respectively. Furthermore, mitragyNiNe was also tested iN vitro for its likelihood to iNhibit APND aNd UGT activity. The assessmeNt of the eNzyme activity was coNducted usiNg spectrophotometric methods. RESULTS: IN vitro, the IC50 value could oNly be obtaiNed for the methaNolic extract iN APND study (595.30±30.78 µg/mL) aNd Not iN other studies due to the eNzyme perceNtage iNhibitioNs beiNg

  • mitragyNa speciosa korth leaves extracts iNduced the cyp450 catalyzed amiNopyriNe N Demethylase apNd aNd udp glucuroNosyl traNsferase ugt activities iN male sprague dawley rat livers
    Drug metabolism and drug interactions, 2013
    Co-Authors: Juzaili Azizi, Sabariah Ismail, Sharif Mahsufi Mansor
    Abstract:

    BACKGROUND: MitragyNa speciosa leaves have beeN abused by drug addicts as some of the alkaloids (maiNly mitragyNiNe) from the plaNt possess opiate aNd cocaiNe-like effects. These briNg to its prohibitioN iN Malaysia iN 2004 as coNsumptioN of M. speciosa leaves has beeN perceived to lead to the abuse of other drugs such as caNNabis aNd heroiN. METHODS: IN the curreNt study, the iN vitro aNd iN vivo effects of M. speciosa methaNolic, aqueous aNd total alkaloid leaves extracts oN drug metaboliziNg eNzymes, Namely, cytochrome P450s (CYP450s) aNd UDP-glucuroNosyl traNsferase (UGT) had beeN evaluated iN rat liver cytosolic fractioN aNd microsomes. AmiNopyriNe aNd p-NitropheNol (pNP) were employed as probe substrates iN amiNopyriNe N-Demethylase (APND) aNd UGT eNzyme assays, respectively. Furthermore, mitragyNiNe was also tested iN vitro for its likelihood to iNhibit APND aNd UGT activity. The assessmeNt of the eNzyme activity was coNducted usiNg spectrophotometric methods. RESULTS: IN vitro, the IC50 value could oNly be obtaiNed for the methaNolic extract iN APND study (595.30±30.78 µg/mL) aNd Not iN other studies due to the eNzyme perceNtage iNhibitioNs beiNg <70%. IN coNtrast to the iN vitro study, the oral treatmeNt of male Sprague-Dawley rats for 14 days with 50, 100 aNd 200 mg/kg of methaNolic aNd aqueous extracts aNd with 5, 10 aNd 20 mg/kg of total alkaloid extract showed a profouNd iNcremeNt oN the APND aNd UGT activities. CONCLUSIONS: The curreNt fiNdiNgs showed that possibilities exist for herb-drug iNteractioN with iNcreased clearaNce of drugs, which are primarily metabolized by CYP450s aNd UGT1A6 amoNg M. speciosa leaves extract users.

  • iN vitro effect of mitragyNiNe oN activity of drug metaboliziNg eNzymes N Demethylase aNd glutathioNe s traNsferase iN streptozotociN iNduced diabetic rats
    2012
    Co-Authors: Rukhsana Anwar, Abas Hj Hussin, Sabariah Ismail, Sharif Mahsufi Mansor
    Abstract:

    MitragyNiNe is the major alkaloid of MitragyNa speciosa Korth. It is respoNsible for aNtiNociceptive, aNtidepressaNt like effects aNd used as substitute for morphiNe to treat opium withdrawal. MitragyNa speciosa plaNt beloNgs to Rubiaceae family. IN Malaysia, the leaves of MitragyNa speciosa are used to treat diarrhea, paiN aNd as cough suppressaNt. FollowiNg experimeNts were uNdertakeN to evaluate the effect of mitragyNiNe oN amiNopyriNe N-Demethylase aNd glutathioNe S-traNsferase activity iN diabetic Sprague-Dawley (SD) male aNd female rats. DiffereNt coNceNtratioNs of mitragyNiNe (0.0025µM-250µM) were used to evaluate activity of both eNzymes. CollageNase perfusioN techNique was used to isolate hepatocytes aNd amiNopyriNe NDemethylase activity was determiNed iN hepatocytes by measuriNg the quaNtity of formaldehyde formed. Rat livers were takeN out aNd cytosolic fractioN was prepared. GST activity was measured iN cytosolic fractioN by kiNetics of thioether product formatioN over time. Results showed that iN diabetic male aNd female SD rat hepatocytes, a sigNificaNt (p< 0.05) iNcrease iN amiNopyriNe N-Demethylase activity was observed oNly with 250µM mitragyNiNe. For phase II drug metaboliziNg eNzyme, mitragyNiNe (0.25µM -250µM) sigNificaNtly (p<0.05) iNhibited the GST specific activity iN both diabetic male aNd female rats. IN coNclusioN this study iNdicates that the amiNopyriNe N-Demethylase eNzyme iNductioN aNd GST activity iNhibitioN by mitragyNiNe is Not iNflueNced by sex. AmiNopyriNe N-Demethylase activity iNcreases oNly oN high coNceNtratioN of mitragyNiNe aNd lower coNceNtratioNs caNNot be able to chaNge it. However GST activity iNhibitioN is dosedepeNdeNt.

Juzaili Azizi - One of the best experts on this subject based on the ideXlab platform.

  • MitragyNa speciosa Korth leaves extracts iNduced the CYP450 catalyzed amiNopyriNe-N-Demethylase (APND) aNd UDP-glucuroNosyl traNsferase (UGT) activities iN male Sprague-Dawley rat livers.
    Drug metabolism and drug interactions, 2013
    Co-Authors: Juzaili Azizi, Sabariah Ismail, Sharif Mahsufi Mansor
    Abstract:

    BACKGROUND: MitragyNa speciosa leaves have beeN abused by drug addicts as some of the alkaloids (maiNly mitragyNiNe) from the plaNt possess opiate aNd cocaiNe-like effects. These briNg to its prohibitioN iN Malaysia iN 2004 as coNsumptioN of M. speciosa leaves has beeN perceived to lead to the abuse of other drugs such as caNNabis aNd heroiN. METHODS: IN the curreNt study, the iN vitro aNd iN vivo effects of M. speciosa methaNolic, aqueous aNd total alkaloid leaves extracts oN drug metaboliziNg eNzymes, Namely, cytochrome P450s (CYP450s) aNd UDP-glucuroNosyl traNsferase (UGT) had beeN evaluated iN rat liver cytosolic fractioN aNd microsomes. AmiNopyriNe aNd p-NitropheNol (pNP) were employed as probe substrates iN amiNopyriNe N-Demethylase (APND) aNd UGT eNzyme assays, respectively. Furthermore, mitragyNiNe was also tested iN vitro for its likelihood to iNhibit APND aNd UGT activity. The assessmeNt of the eNzyme activity was coNducted usiNg spectrophotometric methods. RESULTS: IN vitro, the IC50 value could oNly be obtaiNed for the methaNolic extract iN APND study (595.30±30.78 µg/mL) aNd Not iN other studies due to the eNzyme perceNtage iNhibitioNs beiNg

  • mitragyNa speciosa korth leaves extracts iNduced the cyp450 catalyzed amiNopyriNe N Demethylase apNd aNd udp glucuroNosyl traNsferase ugt activities iN male sprague dawley rat livers
    Drug metabolism and drug interactions, 2013
    Co-Authors: Juzaili Azizi, Sabariah Ismail, Sharif Mahsufi Mansor
    Abstract:

    BACKGROUND: MitragyNa speciosa leaves have beeN abused by drug addicts as some of the alkaloids (maiNly mitragyNiNe) from the plaNt possess opiate aNd cocaiNe-like effects. These briNg to its prohibitioN iN Malaysia iN 2004 as coNsumptioN of M. speciosa leaves has beeN perceived to lead to the abuse of other drugs such as caNNabis aNd heroiN. METHODS: IN the curreNt study, the iN vitro aNd iN vivo effects of M. speciosa methaNolic, aqueous aNd total alkaloid leaves extracts oN drug metaboliziNg eNzymes, Namely, cytochrome P450s (CYP450s) aNd UDP-glucuroNosyl traNsferase (UGT) had beeN evaluated iN rat liver cytosolic fractioN aNd microsomes. AmiNopyriNe aNd p-NitropheNol (pNP) were employed as probe substrates iN amiNopyriNe N-Demethylase (APND) aNd UGT eNzyme assays, respectively. Furthermore, mitragyNiNe was also tested iN vitro for its likelihood to iNhibit APND aNd UGT activity. The assessmeNt of the eNzyme activity was coNducted usiNg spectrophotometric methods. RESULTS: IN vitro, the IC50 value could oNly be obtaiNed for the methaNolic extract iN APND study (595.30±30.78 µg/mL) aNd Not iN other studies due to the eNzyme perceNtage iNhibitioNs beiNg <70%. IN coNtrast to the iN vitro study, the oral treatmeNt of male Sprague-Dawley rats for 14 days with 50, 100 aNd 200 mg/kg of methaNolic aNd aqueous extracts aNd with 5, 10 aNd 20 mg/kg of total alkaloid extract showed a profouNd iNcremeNt oN the APND aNd UGT activities. CONCLUSIONS: The curreNt fiNdiNgs showed that possibilities exist for herb-drug iNteractioN with iNcreased clearaNce of drugs, which are primarily metabolized by CYP450s aNd UGT1A6 amoNg M. speciosa leaves extract users.