title: Effect of Curcuma longa on CYP2D6- and CYP3A4-mediated metabolism of dextromethorphan in human liver microsomes and healthy human subjects.
abstract: Effect of Curcuma longa rhizome powder and its ethanolic extract on CYP2D6 and CYP3A4 metabolic activity was investigated in vitro using human liver microsomes and clinically in healthy human subjects. Dextromethorphan (DEX) was used as common probe for CYP2D6 and CYP3A4 enzymes. Metabolic activity of CYP2D6 and CYP3A4 was evaluated through in vitro study; where microsomes were incubated with NADPH in presence and absence of Curcuma extract. In clinical study phase-I, six healthy human subjects received a single dose (30 mg) of DEX syrup, and in phase-II DEX syrup was administered with Curcuma powder. The enzyme CYP2D6 and CYP3A4 mediated O- and N-demethylation of dextromethorphan into dextrorphan (DOR) and 3-methoxymorphinan (3-MM), respectively. Curcuma extract significantly inhibited the formation of DOR and 3-MM, in a dose-dependent and linear fashion. The 100 μg/ml dose of curcuma extract produced highest inhibition, which was about 70 % for DOR and 80 % for 3-MM. Curcuma significantly increases the urine metabolic ratio of DEX/DOR but the change in DEX/3-MM ratio was statistically insignificant. Present findings suggested that curcuma significantly inhibits the activity of CYP2D6 in in vitro as well as in vivo; which indicates that curcuma has potential to interact with CYP2D6 substrates.
authors: Department of Pharmaceutics, College of Pharmacy, King Saud University, PO Box 2457, Riyadh, 11451, Kingdom of Saudi Arabia, aljenobi@ksu.edu.sa.
authors: Fahad Ibrahim
authors: FI
authors: Al-Jenoobi
authors: Areej A
authors: AA
authors: Al-Thukair
authors: Mohd Aftab
authors: MA
authors: Alam
authors: Fawkeya A
authors: FA
authors: Abbas
authors: Abdullah M
authors: AM
authors: Al-Mohizea
authors: Khalid M
authors: KM
authors: Alkharfy
authors: Saleh A
authors: SA
authors: Al-Suwayeh
mesh_terms: D000293:Adolescent; D000328:Adult; D001711:Biotransformation; D030024:Curcuma / Q000737:chemistry; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism*; D065690:Cytochrome P-450 CYP2D6 Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D003640:Dealkylation; D003915:Dextromethorphan / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D003917:Dextrorphan / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000737:chemistry; D064368:Healthy Volunteers; D041743:Herb-Drug Interactions; D006801:Humans; D016014:Linear Models; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D011208:Powders; D027343:Rhizome; D012529:Saudi Arabia; D012997:Solvents / Q000737:chemistry; D013379:Substrate Specificity; D055815:Young Adult
chemical_list: D065690:Cytochrome P-450 CYP2D6 Inhibitors; D010936:Plant Extracts; D011208:Powders; D012997:Solvents; D003917:Dextrorphan; D000431:Ethanol; C028657:3-methoxymorphinan; D003915:Dextromethorphan; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human