<i>In vitro</i> metabolism of obovatol and its effect on cytochrome P450 enzyme activities in human liver microsomes

Joo, Jeongmin; Lee, Doohyun; Wu, Zhexue; Shin, Jung-Hoon; Lee, Hye Suk; Kwon, Byoung‐Mog; Huh, Tae‐Lin; Kim, Yang-Weon; Lee, Su-Jun; Kim, Tae Wan; Lee, Tae‐Ho; Liu, Kwang-Hyeon

doi:10.1002/bdd.1837

Cited by 8 publications

(5 citation statements)

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“…While lignan exhibited noncompetitive inhibition toward CYP1A2, it proved to be a competitive inhibitor with respect to the other isoforms . In an alternative work, a biophenyl ether lignan obovatol was also shown to inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, and CYP2C19 in vitro , the IC 50 values being 4.4, 13.9, 11.1, 3.3, and 0.8 μM, respectively . The strong potential of lignans to inhibit the catalytic activity of CYP enzymes responsible for drug metabolism suggests the possibility for pharmacokinetic drug interactions.…”

Section: Interactions Between Polyphenols and Cyp: Direct Binding And...mentioning

confidence: 94%

“…137 In an alternative work, a biophenyl ether lignan obovatol was also shown to inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, and CYP2C19 in vitro, the IC 50 values being 4.4, 13.9, 11.1, 3.3, and 0.8 μM, respectively. 140 The strong potential of lignans to inhibit the catalytic activity of CYP enzymes responsible for drug metabolism suggests the possibility for pharmacokinetic drug interactions. The compounds exhibiting mechanism-based inactivation of CYP enzymes and their respective K I ad k inact values are summarized in Table 3.…”

Section: Interactions Between Polyphenols and Cyp: Direct Binding And...mentioning

confidence: 99%

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Effect of Natural Polyphenols on CYP Metabolism: Implications for Diseases

Korobkova

2015

Chem. Res. Toxicol.

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Cytochromes P450 (CYPs) are a large group of hemeproteins located on mitochondrial membranes or the endoplasmic reticulum. They play a crucial role in the metabolism of endogenous and exogenous molecules. The activity of CYP is associated with a number of factors including redox potential, protein conformation, the accessibility of the active site by substrates, and others. This activity may be potentially modulated by a variety of small molecules. Extensive experimental data collected over the past decade point at the active role of natural polyphenols in modulating the catalytic activity of CYP. Polyphenols are widespread micronutrients present in human diets of plant origin and in medicinal herbs. These compounds may alter the activity of CYP either via direct interactions with the enzymes or by affecting CYP gene expression. The polyphenol-CYP interactions may significantly alter the pharmacokinetics of drugs and thus influence the effectiveness of chemical therapies used in the treatment of different types of cancers, diabetes, obesity, and cardiovascular diseases (CVD). CYPs are involved in the oxidation and activation of external carcinogenic agents, in which case the inhibition of the CYP activity is beneficial for health. CYPs also support detoxification processes. In this case, it is the upregulation of CYP genes that would be favorable for the organism. A CYP enzyme aromatase catalyzes the formation of estrone and estradiol from their precursors. CYPs also catalyze multiple reactions leading to the oxidation of estrogen. Estrogen signaling and oxidative metabolism of estrogen are associated with the development of cancer. Thus, polyphenol-mediated modulation of the CYP's activity also plays a vital role in estrogen carcinogenesis. The aim of the present review is to summarize the data collected over the last five to six years on the following topics: (1) the mechanisms of the interactions of CYP with food constituents that occur via the direct binding of polyphenols to the enzymes and (2) the mechanisms of the regulation of CYP gene expression mediated by polyphenols. The structure-activity relationship relevant to the ability of polyphenols to affect the activity of CYP is analyzed. The application of polyphenol-CYP interactions to diseases is discussed.

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Section: Interactions Between Polyphenols and Cyp: Direct Binding And...mentioning

confidence: 94%

Section: Interactions Between Polyphenols and Cyp: Direct Binding And...mentioning

confidence: 99%

Effect of Natural Polyphenols on CYP Metabolism: Implications for Diseases

Korobkova

2015

Chem. Res. Toxicol.

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“…Honokiol weakly inhibited CYP3A-mediated midazolam 1'-hydroxylation with IC 50 values of 97.3 μM. This was not an unusual finding, given that obovatol, a biphenyl ether lignan, also exhibits an inhibitory effect towards CYP1A2, CYP2B6, CYP2C8, CYP2C9, and CYP2C19 with IC 50 values of 4.4, 13.9, 11.1, 3.3, and 0.8 μM, respectively [37]. At 100 μM, honokiol produced negligible inhibition of CYP2A6-mediated coumarin 7-hydroxylation.…”

Section: Resultsmentioning

confidence: 94%

Effect of Honokiol on Cytochrome P450 and UDP-Glucuronosyltransferase Enzyme Activities in Human Liver Microsomes

et al. 2013

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Honokiol is a bioactive component isolated from the medicinal herbs Magnolia officinalis and Magnolia grandiflora that has antioxidative, anti-inflammatory, antithrombotic, and antitumor activities. The inhibitory potentials of honokiol on eight major human cytochrome P450 (CYP) enzymes 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, and 3A4, and four UDP-glucuronosyltransferases (UGTs) 1A1, 1A4, 1A9, and 2B7 in human liver microsomes were investigated using liquid chromatography-tandem mass spectrometry. Honokiol strongly inhibited CYP1A2-mediated phenacetin O-deethylation, CYP2C8-mediated amodiaquine N-deethylation, CYP2C9-mediated diclofenac 4-hydroxylation, CYP2C19-mediated [S]-mephenytoin 4-hydroxylation, and UGT1A9-mediated propofol glucuronidation with K i values of 1.2, 4.9, 0.54, 0.57, and 0.3 μM, respectively. Honokiol also moderately inhibited CYP2B6-mediated bupropion hydroxylation and CYP2D6-mediated bufuralol 1'-hydroxylation with K i values of 17.5 and 12.0 μM, respectively. These in vitro results indicate that honokiol has the potential to cause pharmacokinetic drug interactions with other co-administered drugs metabolized by CYP1A2, CYP2C8, CYP2C9, CYP2C19, and UGT1A9.

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“…The identification of magnolol and honokiol was performed by comparing the fragmentation of their mass spectra with the records in the METLIN online database. The mass spectrum of obovatol was not available from the METLIN database; however, this neolignan was identified based on data published in a paper [ 12 ], in which the fragmentation spectrum of obovatol was published.…”

Section: Resultsmentioning

confidence: 99%

Decorative Magnolia Plants: A Comparison of the Content of Their Biologically Active Components Showing Antimicrobial Effects

Lovecká

Svobodová

Macůrková

et al. 2020

Plants

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Magnolia plants are used both as food supplements and as cosmetic and medicinal products. The objectives of this work consisted of preparing extracts from leaves and flowers of eight Magnolia plants, and of determining concentrations of magnolol (1 to 100 mg·g−1), honokiol (0.11 to 250 mg·g−1), and obovatol (0.09 to 650 mg·g−1), typical neolignans for the genus Magnolia, in extracts made by using a methanol/water (80/20) mixture. The tested Magnolia plants, over sixty years old, were obtained from Průhonický Park (Prague area, Czech Republic): M. tripetala MTR 1531, M. obovata MOB 1511, and six hybrid plants Magnolia × pruhoniciana, results of a crossbreeding of M. tripetala MTR 1531 with M. obovata MOB 1511. The identification of neolignans was performed by HRMS after a reversed-phase high-performance liquid chromatography (RP-HPLC) fractionation of an extract from M. tripetala MTR 1531. The highest concentrations of neolignans were found in the flowers, most often in their reproductive parts, and obovatol was the most abundant in every tested plant. The highest concentrations of neolignans were detected in parent plants, and lower concentrations in hybrid magnolias. Flower extracts from the parent plants M. tripetala MTR 1531 and M. obovata MOB 1511, flower extracts from the hybrid plants Magnolia × pruhoniciana MPR 0271, MPR 0151, and MPR 1531, and leaf extract from the hybrid plant Magnolia × pruhoniciana MPR 0271 inhibited growth of Staphylococcus aureus.

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In vitro metabolism of obovatol and its effect on cytochrome P450 enzyme activities in human liver microsomes

Cited by 8 publications

References 28 publications

Effect of Natural Polyphenols on CYP Metabolism: Implications for Diseases

Effect of Natural Polyphenols on CYP Metabolism: Implications for Diseases

Effect of Honokiol on Cytochrome P450 and UDP-Glucuronosyltransferase Enzyme Activities in Human Liver Microsomes

Decorative Magnolia Plants: A Comparison of the Content of Their Biologically Active Components Showing Antimicrobial Effects

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