Effect of Standardized Cranberry Extract on the Activity and Expression of Selected Biotransformation Enzymes in Rat Liver and Intestine

Bártíková, Hana; Boušová, Iva; Jedličková, Pavla; Lněničková, Kateřina; Skálová, Lenka; Szotáková, Barbora

doi:10.3390/molecules190914948

Cited by 9 publications

(3 citation statements)

References 38 publications

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“…Notably, orally ingested GFJ did not seem to affect hepatic CYP3A4 expression or activity, while decreasing small-intestinal CYP3A4 protein levels by >60% 64 . In contrast, the consumption of cranberry extract, which caused moderate increases in hepatic CYP3A and CYP1A1 activities, did not influence intestinal CYP1A1, CYP1A2, CYP2B and CYP3A expression in rats 65 . GFJ has been employed as a tool to modulate intestinal drug metabolism in numerous studies.…”

Section: Regulation Of Intestinal Cyp Expression and Functionmentioning

confidence: 68%

An update on the role of intestinal cytochrome P450 enzymes in drug disposition

Xie

Ding

Zhang

2016

Acta Pharmaceutica Sinica B

111

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Oral administration is the most commonly used route for drug treatment. Intestinal cytochrome P450 (CYP)-mediated metabolism can eliminate a large proportion of some orally administered drugs before they reach systemic circulation, while leaving the passage of other drugs unimpeded. A better understanding of the ability of intestinal P450 enzymes to metabolize various clinical drugs in both humans and preclinical animal species, including the identification of the CYP enzymes expressed, their regulation, and the relative importance of intestinal metabolism compared to hepatic metabolism, is important for improving bioavailability of current drugs and new drugs in development. Here, we briefly review the expression of drug-metabolizing P450 enzymes in the small intestine of humans and several preclinical animal species, and provide an update of the various factors or events that regulate intestinal P450 expression, including a cross talk between the liver and the intestine. We further compare various clinical and preclinical approaches for assessing the impact of intestinal drug metabolism on bioavailability, and discuss the utility of the intestinal epithelium–specific NADPH-cytochrome P450 reductase-null (IECN) mouse as a useful model for studying in vivo roles of intestinal P450 in the disposition of orally administered drugs.

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Section: Regulation Of Intestinal Cyp Expression and Functionmentioning

confidence: 68%

An update on the role of intestinal cytochrome P450 enzymes in drug disposition

Xie

Ding

Zhang

2016

Acta Pharmaceutica Sinica B

111

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“…PCs are highly efficient natural antioxidants, their antioxidant activity is 50 times higher than that of vitamin E and 20 times that of vitamin C, and their effects have been reported in a wide range of studies [12,27,43,44,45,46,47]. The results of the meta-analysis by Li et al [47] indicated that PCs could effectively improve the activity of anti-oxidative enzymes and reduce lipid peroxidation products.…”

Section: Discussionmentioning

confidence: 99%

Proanthocyanidins Attenuation of Chronic Lead-Induced Liver Oxidative Damage in Kunming Mice via the Nrf2/ARE Pathway

et al. 2016

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Lead is harmful for human health and animals. Proanthocyanidins (PCs), a natural antioxidant, possess a broad spectrum of pharmacological and medicinal properties. However, its protective effects against lead-induced liver damage have not been clarified. This study was aimed to evaluate the protective effect of PCs on the hepatotoxicity of male Kunming mice induced by chronic lead exposure. A total of 70 healthy male Kunming mice were averagely divided into four groups: control group, i.e., the group exposed to lead, the group treated with PCs, and the group co-treated with lead and PCs. The mice exposed to lead were given water containing 0.2% lead acetate. Mice treated in the PCs and PCs lead co-treated groups were given PC (100 mg/kg) in 0.9% saline by oral gavage. Lead exposure caused a significant elevation in the liver function parameters, lead level, lipid peroxidation, and inhibition of antioxidant enzyme activities. The induction of oxidative stress and histological alterations in the liver were minimized by co-treatment with PCs. Meanwhile, the number of Transferase-Mediated Deoxyuridine Triphosphate-Biotin Nick End Labeling (TUNEL)-positive cells was significantly reduced in the PCs/lead co-treated group compared to the lead group. In addition, the lead group showed an increase in the expression level of Bax, while the expression of Bcl-2 was decreased. Furthermore, the lead group showed an increase in the expression level of endoplasmic reticulum (ER) stress-related genes and protein (GRP78 and CHOP). Co-treated with PCs significantly reversed these expressions in the liver. PCs were, therefore, demonstrated to have protective, antioxidant, and anti-ER stress and anti-apoptotic activities in liver damage caused by chronic lead exposure in the Kunming mouse. This may be due to the ability of PCs to enhance the ability of liver tissue to protect against oxidative stress via the Nrf2/ARE signaling pathway, resulting in decreasing ER stress and apoptosis of liver tissue.

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“…Metabolism refers to the chemical structural transformation of drugs [439]. After entering the body, plant polyphenols are metabolized by various enzymes, such as cytochrome P450 [440] and catechol-O-methyltransferase (COMT) [441]. After oral administration of curcumin, its glucuronide conjugates or sulfate conjugates could be detected in the blood [442].…”

Section: Bioavailability Of Plant Polyphenolsmentioning

confidence: 99%

Dietary Plant Polyphenols as the Potential Drugs in Neurodegenerative Diseases: Current Evidence, Advances, and Opportunities

Guo

Zhang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD), are characterized by the progressive degeneration of neurons. Although the etiology and pathogenesis of neurodegenerative diseases have been studied intensively, the mechanism is still in its infancy. In general, most neurodegenerative diseases share common molecular mechanisms, and multiple risks interact and promote the pathologic process of neurogenerative diseases. At present, most of the approved drugs only alleviate the clinical symptoms but fail to cure neurodegenerative diseases. Numerous studies indicate that dietary plant polyphenols are safe and exhibit potent neuroprotective effects in various neurodegenerative diseases. However, low bioavailability is the biggest obstacle for polyphenol that largely limits its adoption from evidence into clinical practice. In this review, we summarized the widely recognized mechanisms associated with neurodegenerative diseases, such as misfolded proteins, mitochondrial dysfunction, oxidative damage, and neuroinflammatory responses. In addition, we summarized the research advances about the neuroprotective effect of the most widely reported dietary plant polyphenols. Moreover, we discussed the current clinical study and application of polyphenols and the factors that result in low bioavailability, such as poor stability and low permeability across the blood-brain barrier (BBB). In the future, the improvement of absorption and stability, modification of structure and formulation, and the combination therapy will provide more opportunities from the laboratory into the clinic for polyphenols. Lastly, we hope that the present review will encourage further researches on natural dietary polyphenols in the treatment of neurodegenerative diseases.

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Effect of Standardized Cranberry Extract on the Activity and Expression of Selected Biotransformation Enzymes in Rat Liver and Intestine

Cited by 9 publications

References 38 publications

An update on the role of intestinal cytochrome P450 enzymes in drug disposition

An update on the role of intestinal cytochrome P450 enzymes in drug disposition

Proanthocyanidins Attenuation of Chronic Lead-Induced Liver Oxidative Damage in Kunming Mice via the Nrf2/ARE Pathway

Dietary Plant Polyphenols as the Potential Drugs in Neurodegenerative Diseases: Current Evidence, Advances, and Opportunities

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