Inhibition of human cytochromes P450 2A6 and 2A13 by flavonoids, acetylenic thiophenes and sesquiterpene lactones from <i>Pluchea indica</i> and <i>Vernonia cinerea</i>

Boonruang, Supattra; Prakobsri, Khanistha; Pouyfung, Phisit; Srisook, Ekaruth; Prasopthum, Aruna; Rongnoparut, Pornpimol; Sarapusit, Songklod

doi:10.1080/14756366.2017.1363741

Cited by 17 publications

(14 citation statements)

References 23 publications

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“…Apigenin was reported to inhibit CYP2A6 activity in the metabolism dependent inhibition assay, as well as the direct inhibition assay of CYP2A6. Boonruanga et al [31] reported similar IC 50 values in metabolism dependent and direct inhibition assays of 0.77 ± 0.16 µM and 0.90 ± 0.07 µM, respectively. Likewise, under the similar experimental conditions and 1 µM concentration of apigenin, we observed comparable values of residual CYP2A6 enzyme activity: 47 ± 7% ( p = 0.037) and 48 ± 1% ( p = 0.018).…”

Section: Resultsmentioning

confidence: 87%

The Effect of Flavonoid Aglycones on the CYP1A2, CYP2A6, CYP2C8 and CYP2D6 Enzymes Activity

et al. 2019

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Cytochromes P450 are major metabolic enzymes involved in the biotransformation of xenobiotics. The majority of xenobiotics are metabolized in the liver, in which the highest levels of cytochromes P450 are expressed. Flavonoids are natural compounds to which humans are exposed through everyday diet. In the previous study, selected flavonoid aglycones showed inhibition of CYP3A4 enzyme. Thus, the objective of this study was to determine if these flavonoids inhibit metabolic activity of CYP1A2, CYP2A6, CYP2C8, and CYP2D6 enzymes. For this purpose, the O-deethylation reaction of phenacetin was used for monitoring CYP1A2 enzyme activity, coumarin 7-hydroxylation for CYP2A6 enzyme activity, 6-α-hydroxylation of paclitaxel for CYP2C8 enzyme activity, and dextromethorphan O-demethylation for CYP2D6 enzyme activity. The generated metabolites were monitored by high-performance liquid chromatography coupled with diode array detection. Hesperetin, pinocembrin, chrysin, isorhamnetin, and morin inhibited CYP1A2 activity; apigenin, tangeretin, galangin, and isorhamnetin inhibited CYP2A6 activity; and chrysin, chrysin-dimethylether, and galangin inhibited CYP2C8. None of the analyzed flavonoids showed inhibition of CYP2D6. The flavonoids in this study were mainly reversible inhibitors of CYP1A2 and CYP2A6, while the inhibition of CYP2C8 was of mixed type (reversible and irreversible). The most prominent reversible inhibitor of CYP1A2 was chrysin, and this was confirmed by the docking study.

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Section: Resultsmentioning

confidence: 87%

The Effect of Flavonoid Aglycones on the CYP1A2, CYP2A6, CYP2C8 and CYP2D6 Enzymes Activity

et al. 2019

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“…Previous studies showed that P. Indica leaf extract contained acetylenic thiophenes, caffeoylquinic acid derivatives, and flavonoids including apigenin, luteolin, and quercetin [13,14,37]. Notably, quercetin inhibited ICAM-1 expression in PMA-and TNF-α-induced ECV304 human endothelial cells by inhibiting the JNK pathway [38].…”

Section: Involvement Of Ho-1 Activation In the Anti-inflammatory Effect Of Pie On Human Endothelial Cellsmentioning

confidence: 98%

Anti-inflammatory and Antioxidant Effects of Pluchea indica Leaf Extract in TNF-α-Induced Human Endothelial Cells

Srisook

Jinda

Srisook

2021

Walailak J Sci & Tech

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Pluchea indica is a shrub plant found in mangrove forests. The leaves are consumed as food and herbal tea and exhibit various biological effects, such as antioxidant and anti-inflammatory activities, in macrophages and animal models. However, the inhibitory activity of P. indica leaf extract on vascular inflammation remains unknown. Therefore, this study investigated the effect of an ethanol extract from P. indica herbal tea leaves (PIE) on tumor necrosis factor-α (TNF-α)-induced human vascular endothelial EA.hy926 cells. The cytotoxic effect of PIE was determined by thiazolyl blue tetrazolium bromide assays. PIE at concentrations of 12.5 - 50 µg/mL did not show significant cytotoxicity, whereas PIE at concentrations ≥ 100 µg/mL decreased cell viability. PIE inhibited the production of reactive oxygen species (ROS) in TNF-α-stimulated endothelial cells. To evaluate the PIE’s anti-vascular inflammatory activity, the protein expression of cell adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), was determined by western blot. PIE significantly decreased TNF-α-induced ICAM-1 and VCAM-1 expression in a concentration-dependent manner. Furthermore, PIE upregulated heme oxygenase-1 (HO-1) in a concentration- and time-dependent manner. Inhibiting the activity of HO-1 by tin protoporphyrin IX significantly blocked the suppressive effect of PIE on ICAM-1 but not VCAM-1 expression. Therefore, PIE exerts anti-inflammatory activity on vascular endothelial cells, at least in part, by suppressing ROS production and the induction of HO-1. The obtained data suggest that PIE is a promising substance for developing therapeutic agents or as an ingredient of functional food. HIGHLIGHTS Pluchea indica leaf extract (PIE) at non-toxic doses inhibited ICAM-1 and VCAM-1 in TNF-α-induced human vascular endothelial cells PIE suppressed the production of ROS in TNF-α-stimulated endothelial cells PIE exerts anti-inflammatory activity on vascular endothelial cells mediated partly through the upregulation of HO-1

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“…[ 13 – 18 ] CYP2A13 can efficiently metabolize and activate aflatoxin B1, generate a variety of metabolites including epoxide, and then combine with DNA, RNA, protein, and other biological macromolecules in the body to form DNA, RNA, and protein adducts to cause cytotoxicity, Inflammation, DNA damage, and other toxic effects, which may cause cell malignant transformation and cause body tumors. [ 19 – 25 ] At present, there is no consistent conclusion on the genetic polymorphism of CYP2A13 and lung cancer susceptibility. Therefore, in this study, the meta-analysis method was used to systematically evaluate the relationship between CYP2A13 gene polymorphism and lung cancer susceptibility, in order to provide a basis for exploring clinical drug targets and cancer prevention.…”

Section: Introductionmentioning

confidence: 99%

Association between CYP2A13 polymorphisms and lung cancer

Jin

Yang

et al. 2020

Medicine

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Background: Recently, lung cancer has become the most common cause of cancer-related death, several studies indicate that the cytochrome P450 2A13 (CYP2A13) polymorphisms may be correlated with lung cancer susceptibility, but the results have been inconsistent and inconclusive. Therefore, the aim of this meta-analysis is to provide a precise conclusion on the potential association between CYP2A13 polymorphisms and the risk of lung cancer based on case-control studies. Methods: The PubMed, Embase, Cochrane Library, Web of Science, and China National Knowledge Infrastructure (CNKI) databases will be searched for case-control studies published up to September 2020. Odds ratio (OR) and 95% confidence interval (95% CI) were used to determine the effects of the CYP2A13 polymorphism on lung cancer risk, respectively. Results: The results of this meta-analysis will be submitted to a peer-reviewed journal for publication. Conclusion: This meta-analysis will summarize the association between CYP2A13 polymorphisms and the risk of lung cancer. INPLASY registration number: INPLASY202090102

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Inhibition of human cytochromes P450 2A6 and 2A13 by flavonoids, acetylenic thiophenes and sesquiterpene lactones from Pluchea indica and Vernonia cinerea

Cited by 17 publications

References 23 publications

The Effect of Flavonoid Aglycones on the CYP1A2, CYP2A6, CYP2C8 and CYP2D6 Enzymes Activity

The Effect of Flavonoid Aglycones on the CYP1A2, CYP2A6, CYP2C8 and CYP2D6 Enzymes Activity

Anti-inflammatory and Antioxidant Effects of Pluchea indica Leaf Extract in TNF-α-Induced Human Endothelial Cells

Association between CYP2A13 polymorphisms and lung cancer

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