Analysis of ginger root essential oil and hydrosol: CYP450 inhibition
- UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
- Xiao Tan (Creator)
- Institution
- The University of North Carolina at Greensboro (UNCG )
- Web Site: http://library.uncg.edu/
- Advisor
- Gregory Raner
Abstract: Former researches showed ginger extracts could contribute to hepatic protection. Two species of cytochrome P450 enzymes, CYP2E1 and CYP2A6, are both important heme-containing liver enzymes for hepatictoxicology via metabolizing small organic molecules into toxic metabolites. CYP2E1 metabolizes more than 2% of all the oral drugs and is closely associated with liver toxicity. CYP2A6 metabolizes fewer than 5% of all the oral drugs and activates some tobacco procarcinogens. Therefore, inhibitors from natural extracts might be able to provide with preventative therapy to liver toxicity and cancer.CYP2E1 inhibitors may be used to inhibit liver toxicity of CYP2E1 in metabolizing the pain killer acetaminophen into toxic N-acetyl-p-quinoimine (NAPQI) to prevent liver cell necrosis. In addition, CYP2A6 inhibitors may be used to suppress the metabolism of certain pro-carcinogensthat are inhaled from smoking. In this research, two extracts from steam distillation of ginger root, ginger essential oil and ginger hydrosol, were collected. CYP2E1 and CYP2A6 were assayed with presence of the two extracts at a series of concentrations to test the ginger extracts’ dose-dependent effects. The results showed both of the two extractsas CYP2E1 inhibitors but as poor inhibitors to CYP2A6. The major organic contents of ginger essential oil and ginger hydrosol were identified by GC-MS. The results showed both of them contained citral. The major organic components of ginger hydrosol were determined as citral (neral and geranial), 2-heptanol and eucalyptol. The Michaelis-Menten kinetic analysis showed that ginger essential oil, citral, and ginger hydrosol were all competitive inhibitors to CYP2E1 from human liver S9 fraction. The KI for Brazilian ginger essential oil was 27.3mg/L and the KI for Costa Rican ginger essential oil was 29.9 mg/L.The inhibitory constant of citral was KI of 43.0µM. Meanwhile, the KI for Brazilian ginger hydrosol was 4.6% of its original concentration, which corresponded to 45.5 µM citral (neral: geranial=1:1.4).The KI for the Brazilian ginger hydrosol was 3.6% of its original concentration, which corresponded to 44.3µM citral (neral: geranial=1:1.4). Citral was implicated to be the most potent inhibitor from ginger hydrosol to human liver CYP2E1.Ginger hydrosol and citral were shown to be inhibitors to purified human liver CYP2E1 in the metabolism of acetaminophen to NAPQI by analysis with LC-MS. In the presence of the substrate acetaminophen at 800µM, the concentration close to its toxic concentration, Brazilian ginger hydrosol exhibited a 50% inhibition of enzyme activity at the concentration over 25%. This concentration of Brazilian ginger hydrosol corresponds to a dose of citral of around 158 µM. This result implicated that ginger hydrosol and citral could be used as a natural therapeutic for toxicity of acetaminophen.
Analysis of ginger root essential oil and hydrosol: CYP450 inhibition
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Created on 12/1/2015
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Additional Information
- Publication
- Thesis
- Language: English
- Date: 2015
- Keywords
- Acetaminophen, CYP2E1, Essential Oil, Ginger Root, Hydrosol, Liver Toxicity
- Subjects
- Cytochrome P-450 $x Inhibitors
- Cytochrome P-450 CYP2E1 $x Inhibitors
- Enzyme inhibitors
- Ginger $x Physiological effect
- Essences and essential oils $x Physiological effect
- Acetaminophen $x Toxicology
- Hepatotoxicology