Institute of Biopharmaceutical science

Tainan, Taiwan

Institute of Biopharmaceutical science

Tainan, Taiwan
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Lo S.-N.,National Research Institute of Chinese Medicine | Lo S.-N.,Institute of Biopharmaceutical science | Shen C.-C.,National Research Institute of Chinese Medicine | Chang C.-Y.,National Research Institute of Chinese Medicine | And 8 more authors.
Drug Metabolism and Disposition | Year: 2015

The protoberberine alkaloid berberine carries methylenedioxy moiety and exerts a variety of pharmacological effects, such as antiinflammation and lipid-lowering effects. Berberine causes potent CYP1B1 inhibition, whereas CYP1A2 shows resistance to the inhibition. To reveal the influence of oxidative metabolism on CYP1 inhibition by berberine, berberine oxidation and the metabolitemediated inhibition were determined. After NADPH-fortified preincubation of berberine with P450, the inhibition of CYP1A1 and CYP1B1 variants (CYP1B1.1, CYP1B1.3, and CYP1B1.4) by berberine was not enhanced, and CYP1A2 remained resistant. Demethyleneberberine was identified as the most abundant metabolite of CYP1A1- and CYP1B1-catalyzed oxidations, and thalifendine was generated at a relatively low rate. CYP1A1-catalyzed berberine oxidation had the highest maximal velocity (Vmax) and exhibited positive cooperativity, suggesting the assistance of substrate binding when the first substrate was present. In contrast, the demethylenation by CYP1B1 showed the property of substrate inhibition. CYP1B1- catalyzed berberine oxidation had low Km values, but it had Vmax values less than 8% of those of CYP1A1. The dissociation constants generated from the binding spectrum and fluorescence quenching suggested that the low Km values of CYP1B1-catalyzed oxidation might include more than the rate constants describing berberine binding. The natural protoberberine/berberine fmetabolites with methylenedioxy ring-opening (palmatine, jatrorrhizine, and demethyleneberberine) and the demethylation (thalifendine and berberrubine) caused weak CYP1 inhibition. These results demonstrated that berberine was not efficiently oxidized by CYP1B1, and metabolism-dependent irreversible inactivation was minimal. Metabolites of berberine caused a relatively weak inhibition of CYP1. © 2015 by The American Society for Pharmacology and Experimental Therapeutics.


Yeh Y.-C.,National Cheng Kung University | Wu H.-J.,National Cheng Kung University | Huang W.-S.,U.S. Food and Drug Administration | Lin C.-C.,U.S. Food and Drug Administration | And 4 more authors.
Journal of AOAC International | Year: 2011

An isocratic HPLC method routinely used in the National Laboratory for Food and Drug Analysis of Taiwan was validated for the simultaneous determination of six aminophenols and phenylenediamines in commercial hair dyes. After extraction of the commercial hair dye product, the dye intermediates were determined by HPLC. Recoveries from the extraction were between 91.6 and 96.5%. The method was then evaluated in an interlaboratory collaborative study according to AOAC guidelines. Five laboratories in Taiwan participated in the study that analyzed the test product, which was preanalyzed by two laboratories to ensure acceptable homogeneity. The RSDr and RSDR values of the measurements obtained for the dye intermediates in the product were ≤3.75 and ≤5.95%, respectively. The method demonstrated acceptable reproducibility, as evidenced by HorRat values of 0.82-0.97. The applicability of the method to the determination of oxidative hair dye components was further demonstrated in analyses of two different products. The method is thus proposed to be used by manufacturers and laboratories to evaluate the quality of commercial hair dyes containing the six aminophenols and phenylenediamines.

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