Cytochrome P3A4 Inhibitors and Other Constituents of <i>Fibraurea tinctoria</i>

Su, Chung‐Ren; Ueng, Yune-Fang; Dũng, Nguyên Xuân; Reddy, Mopur Vijaya Bhaskar; Wu, Tong

doi:10.1021/np0704248

Cited by 30 publications

(19 citation statements)

References 13 publications

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“…Our results on berberine in the study are in accordance with these previous results, and verify them. Palmatine and jateorrhizine showed an inhibitory effect against CYP3A4 with IC 50 values of 0.9 µ m and 2.1 µ m (Su et al , ). The two values were markedly lower than our values, the difference was likely to have something to do with the origin of human CYP3A4.…”

Section: Discussionmentioning

confidence: 99%

In Vitro Inhibition of Huanglian [Rhizoma coptidis (L.)] and its Six Active Alkaloids on Six Cytochrome P450 Isoforms in Human Liver Microsomes

Han

et al. 2011

Phytotherapy Research

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Huanglian (Rhizoma Coptidis) as a popular herb has been used for the treatment of various diseases such as diarrhea, eye inflammation and women's abdominal ailments. Alkaloids are considered to be responsible for its pharmacological effects. In this investigation, Huanglian and its six alkaloids (coptisine, epiberberine, berberine, jateorrhizine, palmatine and magnoflorine) were systematically evaluated for their inhibition of six cytochrome P450 isoforms (CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4) in human liver microsomes by the LC-MS/MS method. Huanglian showed the strongest inhibition of CYP2D6, followed by CYP1A2 and CYP3A4_T. The IC₅₀ values were 5.8 µg/mL, 36.8 µg/mL and 59.2 µg/mL, respectively. Of the constituents tested, coptisine and epiberberine showed strong inhibition of CYP2D6 with IC₅₀ values of 4.4 µM and 7.7 µM; berberine, jateorrhizine and palmatine showed weak inhibition of CYP2D6 with IC₅₀ values of 45.5 µM, 49.4 µM and 92.6 µM, respectively; jateorrhizine showed moderate inhibition of CYP3A4_T with an IC₅₀ value of 13.3 µM; coptisine showed weak inhibition of CYP1A2 with an IC₅₀ value of 37.3 µM. In addition, activation was observed in coptisine/CYP2C9 and palmatine/CYP2C9/CYP2C19. Other CYP450 isoforms were not affected markedly by the six alkaloids. In conclusion, Huanglian showed in vitro inhibition of CYP2D6, the inhibition might be contributed mostly by protoberberine alkaloids, especially coptisine and epiberberine. Herb-drug interactions may occur through the CYP2D6 inhibition.

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Section: Discussionmentioning

confidence: 99%

In Vitro Inhibition of Huanglian [Rhizoma coptidis (L.)] and its Six Active Alkaloids on Six Cytochrome P450 Isoforms in Human Liver Microsomes

Han

et al. 2011

Phytotherapy Research

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“…254 Compound 647 , a stereoisomer of 8-hydroxycolumbin at the C-12 position, contains the same C-1(18)-lactone ring as 641 rather than the C-2(18)-lactone ring of compounds 648 and 649 . 258 Compounds 650–653 are novel furano-clerodanes from Dioscorea antaly and D. bulbifera with a second δ-lactone ring bridging carbonyl C-19 to C-2.…”

Section: Structure Classifications and Sources Of Clerodane Diterpmentioning

confidence: 99%

“…254,357 Compounds 970–972 , isolated from Tinospora sinensis , were subjected to an α-glucosidase inhibition assay, and exhibited IC 50 values of 2.9, 3.8, 3.3, and 1.9 mM, respectively. Meanwhile, the positive control, acarbose, demonstrated an IC 50 value of 0.84 μM.…”

Section: Structure Classifications and Sources Of Clerodane Diterpmentioning

confidence: 99%

Clerodane diterpenes: sources, structures, and biological activities

2016

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The clerodane diterpenoids are a widespread class of secondary metabolites and have been found in several hundreds of plant species from various families and in organisms from other taxonomic groups. These substances have attracted interest in recent years due to their notable biological activities, particularly insect antifeedant properties. In addition, the major active clerodanes of Salvia divinorum can be used as novel opioid receptor probes, allowing greater insight into opioid receptor-mediated phenomena, as well as opening additional areas for chemical investigation. This article provides extensive coverage of naturally occurring clerodane diterpenes discovered from 1990 until 2015, and follows up on the 1992 review by Merritt and Ley in this same journal. The distribution, chemotaxonomic significance, chemical structures, and biological activities of clerodane diterpenes are summarized. In the cases where sufficient information is available, structure activity relationship (SAR) correlations and mode of action of active clerodanes have been presented.

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“…Berberine chloride, glucose-6-phosphate, glucose-6-phosphate dehydrogenase (yeast), and b-NADP + sodium salt were purchased from Sigma-Aldrich (St. Louis, MO). Palmatine and jatrorrhizine were isolated and purified from Fibraurea tinctoria by T. S. Wu (Department of Chemistry, National Chung-Kung University, Tainan, Taiwan, ROC) following the method as previously described (Su et al, 2007). Berberrubine, demethyleneberberine, and thalifendine were synthesized by C. C. Sheng (Division of Chinese Medicinal Chemistry, National Research Institute of Chinese Medicine, Taipei, Taiwan, ROC) following the methods reported by Liu et al (2009Liu et al ( , 2010.…”

Section: Methodsmentioning

confidence: 99%

“…Berberrubine, demethyleneberberine, and thalifendine were synthesized by C. C. Sheng (Division of Chinese Medicinal Chemistry, National Research Institute of Chinese Medicine, Taipei, Taiwan, ROC) following the methods reported by Liu et al (2009Liu et al ( , 2010. The structures of isolated natural products and synthetic metabolites were identified by 1 H-NMR and 13 C-NMR analyses (Su et al, 2007;Bodiwala et al, 2011). The purities of synthetic metabolites were $98% based on the NMR and high-performance liquid chromatography (HPLC) analyses.…”

Section: Methodsmentioning

confidence: 99%

The Effect of Oxidation on Berberine-Mediated CYP1 Inhibition: Oxidation Behavior and Metabolite-Mediated Inhibition

Shen

Chang

et al. 2015

Drug Metab Dispos

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The protoberberine alkaloid berberine carries methylenedioxy moiety and exerts a variety of pharmacological effects, such as anti-inflammation 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 metabolite-mediated 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 (V max) 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 K m values, but it had V max values less than 8% of those of CYP1A1. The dissociation constants generated from the binding spectrum and fluorescence quenching suggested that the low K m 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.

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Cytochrome P3A4 Inhibitors and Other Constituents of Fibraurea tinctoria

Cited by 30 publications

References 13 publications

In Vitro Inhibition of Huanglian [Rhizoma coptidis (L.)] and its Six Active Alkaloids on Six Cytochrome P450 Isoforms in Human Liver Microsomes

In Vitro Inhibition of Huanglian [Rhizoma coptidis (L.)] and its Six Active Alkaloids on Six Cytochrome P450 Isoforms in Human Liver Microsomes

Clerodane diterpenes: sources, structures, and biological activities

The Effect of Oxidation on Berberine-Mediated CYP1 Inhibition: Oxidation Behavior and Metabolite-Mediated Inhibition

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