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result sql = Effects of spice constituents on P-glycoprotein-mediated transport and CYP3A4-mediated metabolism in vitro.
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result sql = The effects of eight components from six commonly consumed spices on P-glycoprotein (P-gp) transport and CYP3A4 metabolism were evaluated in vitro. P-gp-mediated [(3)H]digoxin fluxes across the L-MDR1 (LLC-PK1 cells transfected with human MDR1 gene) and Caco-2 (human colon carcinoma) cell monolayers showed a marked asymmetry compared with that in the LLC-PK1 (porcine kidney epithelial cells) cell monolayers. Curcumin (from turmeric) at 30 to 60 microM and 6-gingerol (from ginger) at 100 to 500 microM were observed to inhibit P-gp-mediated [(3)H]digoxin transport in L-MDR1 and Caco-2 cells. Effects of spices on midazolam (MDZ) 1'-hydroxylation and 4-hydroxylation of CYP3A4 activity were determined in pooled human liver microsomes (HLM). The following IC(50) values for effects of spices on MDZ 1'-hydroxylation in HLM were obtained: 29 microM for curcumin, 1.17 mM for allyl methyl disulfide (AMD) (from Chinese chive), 1.02 mM for 1,8-cineole (from coriander), and 1.28 mM for beta-caryophyllene (from curry leaf). CYP3A4-mediated 4-hydroxylation of MDZ was inhibited by curcumin at 30, 45, and 60 microM (4-hydroxy-MDZ formation was decreased to 52, 30, and 29%, respectively, compared with control), by 6-gingerol at 60, 100, and 500 microM (71, 68, and 38%), by AMD at 1 and 4 mM (29 and 14%), by d-limonene (from coriander) at 4 mM (65%), by 1,8-cineole at 0.5, 1, and 4 mM (74, 64, and 59%), and by citral (from lemongrass) at 1 mM (59%). Among the spices that showed inhibitory effect on MDZ metabolism in HLM, only AMD showed a preincubation time-dependent inhibitory effect on MDZ metabolism in HLM, suggesting the AMD as an irreversible CYP3A4 inhibitor.
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char = C;code = 67
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char = v;code = 118
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char = o;code = 111
char = .;code = 46
result sql = Effects of spice constituents on P-glycoprotein-mediated transport and CYP3A4-mediated metabolism in vitro.
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char = e;code = 101
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char = ;code = 32
char = i;code = 105
char = n;code = 110
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char = v;code = 118
char = i;code = 105
char = t;code = 116
char = r;code = 114
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char = .;code = 46
char = ;code = 32
char = P;code = 80
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char = g;code = 103
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char = m;code = 109
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char = [;code = 91
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char = H;code = 72
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char = L;code = 76
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char = R;code = 82
char = 1;code = 49
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char = (;code = 40
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char = L;code = 76
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char = K;code = 75
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char = f;code = 102
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char = h;code = 104
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char = a;code = 97
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char = M;code = 77
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char = 1;code = 49
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char = s;code = 115
char = h;code = 104
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char = m;code = 109
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char = m;code = 109
char = e;code = 101
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char = t;code = 116
char = h;code = 104
char = a;code = 97
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char = h;code = 104
char = e;code = 101
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char = L;code = 76
char = L;code = 76
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char = o;code = 111
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char = a;code = 97
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char = s;code = 115
char = .;code = 46
char = ;code = 32
char = C;code = 67
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char = r;code = 114
char = c;code = 99
char = u;code = 117
char = m;code = 109
char = i;code = 105
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char = ;code = 32
char = (;code = 40
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char = ;code = 32
char = H;code = 72
char = L;code = 76
char = M;code = 77
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = b;code = 98
char = t;code = 116
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = d;code = 100
char = :;code = 58
char = ;code = 32
char = 2;code = 50
char = 9;code = 57
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = r;code = 114
char = o;code = 111
char = M;code = 77
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = c;code = 99
char = u;code = 117
char = r;code = 114
char = c;code = 99
char = u;code = 117
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = 1;code = 49
char = .;code = 46
char = 1;code = 49
char = 7;code = 55
char = ;code = 32
char = m;code = 109
char = M;code = 77
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = y;code = 121
char = l;code = 108
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = t;code = 116
char = h;code = 104
char = y;code = 121
char = l;code = 108
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = s;code = 115
char = u;code = 117
char = l;code = 108
char = f;code = 102
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = ;code = 32
char = (;code = 40
char = A;code = 65
char = M;code = 77
char = D;code = 68
char = );code = 41
char = ;code = 32
char = (;code = 40
char = f;code = 102
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = ;code = 32
char = C;code = 67
char = h;code = 104
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = );code = 41
char = ,;code = 44
char = ;code = 32
char = 1;code = 49
char = .;code = 46
char = 0;code = 48
char = 2;code = 50
char = ;code = 32
char = m;code = 109
char = M;code = 77
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = 1;code = 49
char = ,;code = 44
char = 8;code = 56
char = -;code = 45
char = c;code = 99
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = o;code = 111
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = (;code = 40
char = f;code = 102
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = r;code = 114
char = i;code = 105
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = e;code = 101
char = r;code = 114
char = );code = 41
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 1;code = 49
char = .;code = 46
char = 2;code = 50
char = 8;code = 56
char = ;code = 32
char = m;code = 109
char = M;code = 77
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = -;code = 45
char = c;code = 99
char = a;code = 97
char = r;code = 114
char = y;code = 121
char = o;code = 111
char = p;code = 112
char = h;code = 104
char = y;code = 121
char = l;code = 108
char = l;code = 108
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = (;code = 40
char = f;code = 102
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = ;code = 32
char = c;code = 99
char = u;code = 117
char = r;code = 114
char = r;code = 114
char = y;code = 121
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = a;code = 97
char = f;code = 102
char = );code = 41
char = .;code = 46
char = ;code = 32
char = C;code = 67
char = Y;code = 89
char = P;code = 80
char = 3;code = 51
char = A;code = 65
char = 4;code = 52
char = -;code = 45
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = 4;code = 52
char = -;code = 45
char = h;code = 104
char = y;code = 121
char = d;code = 100
char = r;code = 114
char = o;code = 111
char = x;code = 120
char = y;code = 121
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = M;code = 77
char = D;code = 68
char = Z;code = 90
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = c;code = 99
char = u;code = 117
char = r;code = 114
char = c;code = 99
char = u;code = 117
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = 3;code = 51
char = 0;code = 48
char = ,;code = 44
char = ;code = 32
char = 4;code = 52
char = 5;code = 53
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 6;code = 54
char = 0;code = 48
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = r;code = 114
char = o;code = 111
char = M;code = 77
char = ;code = 32
char = (;code = 40
char = 4;code = 52
char = -;code = 45
char = h;code = 104
char = y;code = 121
char = d;code = 100
char = r;code = 114
char = o;code = 111
char = x;code = 120
char = y;code = 121
char = -;code = 45
char = M;code = 77
char = D;code = 68
char = Z;code = 90
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = 5;code = 53
char = 2;code = 50
char = ,;code = 44
char = ;code = 32
char = 3;code = 51
char = 0;code = 48
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 2;code = 50
char = 9;code = 57
char = %;code = 37
char = ,;code = 44
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = p;code = 112
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = y;code = 121
char = ,;code = 44
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = );code = 41
char = ,;code = 44
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = 6;code = 54
char = -;code = 45
char = g;code = 103
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = e;code = 101
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = ;code = 32
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = 6;code = 54
char = 0;code = 48
char = ,;code = 44
char = ;code = 32
char = 1;code = 49
char = 0;code = 48
char = 0;code = 48
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 5;code = 53
char = 0;code = 48
char = 0;code = 48
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = r;code = 114
char = o;code = 111
char = M;code = 77
char = ;code = 32
char = (;code = 40
char = 7;code = 55
char = 1;code = 49
char = ,;code = 44
char = ;code = 32
char = 6;code = 54
char = 8;code = 56
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 3;code = 51
char = 8;code = 56
char = %;code = 37
char = );code = 41
char = ,;code = 44
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = A;code = 65
char = M;code = 77
char = D;code = 68
char = ;code = 32
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = 1;code = 49
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 4;code = 52
char = ;code = 32
char = m;code = 109
char = M;code = 77
char = ;code = 32
char = (;code = 40
char = 2;code = 50
char = 9;code = 57
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 1;code = 49
char = 4;code = 52
char = %;code = 37
char = );code = 41
char = ,;code = 44
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = d;code = 100
char = -;code = 45
char = l;code = 108
char = i;code = 105
char = m;code = 109
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = (;code = 40
char = f;code = 102
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = r;code = 114
char = i;code = 105
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = e;code = 101
char = r;code = 114
char = );code = 41
char = ;code = 32
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = 4;code = 52
char = ;code = 32
char = m;code = 109
char = M;code = 77
char = ;code = 32
char = (;code = 40
char = 6;code = 54
char = 5;code = 53
char = %;code = 37
char = );code = 41
char = ,;code = 44
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = 1;code = 49
char = ,;code = 44
char = 8;code = 56
char = -;code = 45
char = c;code = 99
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = o;code = 111
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = 0;code = 48
char = .;code = 46
char = 5;code = 53
char = ,;code = 44
char = ;code = 32
char = 1;code = 49
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 4;code = 52
char = ;code = 32
char = m;code = 109
char = M;code = 77
char = ;code = 32
char = (;code = 40
char = 7;code = 55
char = 4;code = 52
char = ,;code = 44
char = ;code = 32
char = 6;code = 54
char = 4;code = 52
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 5;code = 53
char = 9;code = 57
char = %;code = 37
char = );code = 41
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = c;code = 99
char = i;code = 105
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = (;code = 40
char = f;code = 102
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = m;code = 109
char = o;code = 111
char = n;code = 110
char = g;code = 103
char = r;code = 114
char = a;code = 97
char = s;code = 115
char = s;code = 115
char = );code = 41
char = ;code = 32
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = 1;code = 49
char = ;code = 32
char = m;code = 109
char = M;code = 77
char = ;code = 32
char = (;code = 40
char = 5;code = 53
char = 9;code = 57
char = %;code = 37
char = );code = 41
char = .;code = 46
char = ;code = 32
char = A;code = 65
char = m;code = 109
char = o;code = 111
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = p;code = 112
char = i;code = 105
char = c;code = 99
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = s;code = 115
char = h;code = 104
char = o;code = 111
char = w;code = 119
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = y;code = 121
char = ;code = 32
char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = M;code = 77
char = D;code = 68
char = Z;code = 90
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = b;code = 98
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = s;code = 115
char = m;code = 109
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = H;code = 72
char = L;code = 76
char = M;code = 77
char = ,;code = 44
char = ;code = 32
char = o;code = 111
char = n;code = 110
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = A;code = 65
char = M;code = 77
char = D;code = 68
char = ;code = 32
char = s;code = 115
char = h;code = 104
char = o;code = 111
char = w;code = 119
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = u;code = 117
char = b;code = 98
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = i;code = 105
char = m;code = 109
char = e;code = 101
char = -;code = 45
char = d;code = 100
char = e;code = 101
char = p;code = 112
char = e;code = 101
char = n;code = 110
char = d;code = 100
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = y;code = 121
char = ;code = 32
char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = M;code = 77
char = D;code = 68
char = Z;code = 90
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = b;code = 98
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = s;code = 115
char = m;code = 109
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = H;code = 72
char = L;code = 76
char = M;code = 77
char = ,;code = 44
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = g;code = 103
char = g;code = 103
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = A;code = 65
char = M;code = 77
char = D;code = 68
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = r;code = 114
char = r;code = 114
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = s;code = 115
char = i;code = 105
char = b;code = 98
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = C;code = 67
char = Y;code = 89
char = P;code = 80
char = 3;code = 51
char = A;code = 65
char = 4;code = 52
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
result sql = The effects of eight components from six commonly consumed spices on P-glycoprotein (P-gp) transport and CYP3A4 metabolism were evaluated in vitro. P-gp-mediated [(3)H]digoxin fluxes across the L-MDR1 (LLC-PK1 cells transfected with human MDR1 gene) and Caco-2 (human colon carcinoma) cell monolayers showed a marked asymmetry compared with that in the LLC-PK1 (porcine kidney epithelial cells) cell monolayers. Curcumin (from turmeric) at 30 to 60 microM and 6-gingerol (from ginger) at 100 to 500 microM were observed to inhibit P-gp-mediated [(3)H]digoxin transport in L-MDR1 and Caco-2 cells. Effects of spices on midazolam (MDZ) 1'-hydroxylation and 4-hydroxylation of CYP3A4 activity were determined in pooled human liver microsomes (HLM). The following IC(50) values for effects of spices on MDZ 1'-hydroxylation in HLM were obtained: 29 microM for curcumin, 1.17 mM for allyl methyl disulfide (AMD) (from Chinese chive), 1.02 mM for 1,8-cineole (from coriander), and 1.28 mM for beta-caryophyllene (from curry leaf). CYP3A4-mediated 4-hydroxylation of MDZ was inhibited by curcumin at 30, 45, and 60 microM (4-hydroxy-MDZ formation was decreased to 52, 30, and 29%, respectively, compared with control), by 6-gingerol at 60, 100, and 500 microM (71, 68, and 38%), by AMD at 1 and 4 mM (29 and 14%), by d-limonene (from coriander) at 4 mM (65%), by 1,8-cineole at 0.5, 1, and 4 mM (74, 64, and 59%), and by citral (from lemongrass) at 1 mM (59%). Among the spices that showed inhibitory effect on MDZ metabolism in HLM, only AMD showed a preincubation time-dependent inhibitory effect on MDZ metabolism in HLM, suggesting the AMD as an irreversible CYP3A4 inhibitor.
Publication: Drug Metab. Dispos. 2008 Jul ;36(7)::1283-90. :doi: 10.1124/dmd.107.019737.
Publication Date: 2008 Jul
Study Author(s): Zhang, Wenxia;Lim, Lee-Yong;
Institution: Department of Pharmacy, National University of Singapore, Singapore.
Shortcut link to this study:
Publication Date: 2008 Jul
Study Author(s): Zhang, Wenxia;Lim, Lee-Yong;
Institution: Department of Pharmacy, National University of Singapore, Singapore.
Shortcut link to this study:
The effects of eight components from six commonly consumed spices on P-glycoprotein (P-gp) transport and CYP3A4 metabolism were evaluated in vitro. P-gp-mediated [(3)H]digoxin fluxes across the L-MDR1 (LLC-PK1 cells transfected with human MDR1 gene) and Caco-2 (human colon carcinoma) cell monolayers showed a marked asymmetry compared with that in the LLC-PK1 (porcine kidney epithelial cells) cell monolayers. Curcumin (from turmeric) at 30 to 60 microM and 6-gingerol (from ginger) at 100 to 500 microM were observed to inhibit P-gp-mediated [(3)H]digoxin transport in L-MDR1 and Caco-2 cells. Effects of spices on midazolam (MDZ) 1'-hydroxylation and 4-hydroxylation of CYP3A4 activity were determined in pooled human liver microsomes (HLM). The following IC(50) values for effects of spices on MDZ 1'-hydroxylation in HLM were obtained: 29 microM for curcumin, 1.17 mM for allyl methyl disulfide (AMD) (from Chinese chive), 1.02 mM for 1,8-cineole (from coriander), and 1.28 mM for beta-caryophyllene (from curry leaf). CYP3A4-mediated 4-hydroxylation of MDZ was inhibited by curcumin at 30, 45, and 60 microM (4-hydroxy-MDZ formation was decreased to 52, 30, and 29%, respectively, compared with control), by 6-gingerol at 60, 100, and 500 microM (71, 68, and 38%), by AMD at 1 and 4 mM (29 and 14%), by d-limonene (from coriander) at 4 mM (65%), by 1,8-cineole at 0.5, 1, and 4 mM (74, 64, and 59%), and by citral (from lemongrass) at 1 mM (59%). Among the spices that showed inhibitory effect on MDZ metabolism in HLM, only AMD showed a preincubation time-dependent inhibitory effect on MDZ metabolism in HLM, suggesting the AMD as an irreversible CYP3A4 inhibitor.
PMID: 18385293
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