Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/13190
Title: Effect of spices on P-gp and CYP3A function and expression
Authors: ZHANG WENXIA
Keywords: spices, P-gp, CYP3A, function, expression
Issue Date: 20-Mar-2008
Source: ZHANG WENXIA (2008-03-20). Effect of spices on P-gp and CYP3A function and expression. ScholarBank@NUS Repository.
Abstract: This project evaluated spice effects on the function and expression of the P-glycoprotein (P-gp) efflux transporter and CYP3A metabolic enzyme. Preliminary screening of spice components showed curcumin and 6-gingerol to inhibit [3H]-digoxin efflux transport in a manner consistent with P-gp inhibition, curcumin being the more potent inhibitor. Both components also affected CYP3A-mediated midazolam (MDZ) 1b 2-hydroxylation and 4-hydroxylation in the human liver microsomes. Intragastric gavage of rats with 60 mg/kg/day of curcumin for 4 consecutive days down-regulated the intestinal P-gp protein level, and up-regulated the hepatic P-gp protein, although the renal P-gp level was unaffected. Curcumin also attenuated CYP3A protein level in the small intestine, but induced CYP3A expression in the liver and kidney. These in turn increased the area under the concentration-time curve (AUC0-8 and total AUC) of peroral celiprolol (P-gp substrate, 30 mg/kg) and MDZ (20 mg/kg), and reduced the apparent oral clearance (CLoral) of the drugs.
URI: http://scholarbank.nus.edu.sg/handle/10635/13190
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01cover.pdf11.71 kBAdobe PDF

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02Proceedings.pdf155.75 kBAdobe PDF

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03Chapter 1 introduction.pdf467.66 kBAdobe PDF

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04Chapter 2 Pgp CYP3A function.pdf530.98 kBAdobe PDF

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05Chapter 3 curcumin 6-gingerol cell growth.pdf131.63 kBAdobe PDF

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06Chapter 4 Pgp expression in vitro.pdf406.93 kBAdobe PDF

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07Chapter 5 Pgp CYP3A expression PK in vivo.pdf499.73 kBAdobe PDF

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08Chapter 6 Final conclusion.pdf86.02 kBAdobe PDF

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09Chapter 7 Future directions.pdf19.76 kBAdobe PDF

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10references.pdf336.8 kBAdobe PDF

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11Appendix.pdf190.33 kBAdobe PDF

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