Phytochemical and Over-The-Counter Drug Interactions: Involvement of Phase I and II Drug-Metabolizing Enzymes and Phase III Transporters

Truong, Van-Long; Jun, Mira; Jeong, Woo-Sik

doi:10.1089/jmf.2021.k.0003

Cited by 7 publications

(6 citation statements)

References 172 publications

(179 reference statements)

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“…Basically, phase II DMEs are enzyme superfamilies, consisting of families and subfamilies of genes encoding isoforms with different tissue expression and regulation, substrate specificities, and pattern of induction/inhibition by xenobiotics. Human UGTs, GSTs and SULTs are the main conjugative DMEs, participating in the metabolism of drugs most commonly used in therapy [ 4 , 175 , 176 ]. At present, limited information is available about SULT expression, regulation and catalytic activity [ 177 ], but phenol and 2-naphthol have already been used as probe substrates in ruminants [ 98 , 100 , 102 ].…”

Section: Discussionmentioning

confidence: 99%

Induction by Phenobarbital of Phase I and II Xenobiotic-Metabolizing Enzymes in Bovine Liver: An Overall Catalytic and Immunochemical Characterization

Cantiello

Carletti

Giantin

et al. 2022

IJMS

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In cattle, phenobarbital (PB) upregulates target drug-metabolizing enzyme (DME) mRNA levels. However, few data about PB’s post-transcriptional effects are actually available. This work provides the first, and an almost complete, characterization of PB-dependent changes in DME catalytic activities in bovine liver using common probe substrates and confirmatory immunoblotting investigations. As expected, PB increased the total cytochrome P450 (CYP) content and the extent of metyrapone binding; moreover, an augmentation of protein amounts and related enzyme activities was observed for known PB targets such as CYP2B, 2C, and 3A, but also CYP2E1. However, contradictory results were obtained for CYP1A, while a decreased catalytic activity was observed for flavin-containing monooxygenases 1 and 3. The barbiturate had no effect on the chosen hydrolytic and conjugative DMEs. For the first time, we also measured the 26S proteasome activity, and the increase observed in PB-treated cattle would suggest this post-translational event might contribute to cattle DME regulation. Overall, this study increased the knowledge of cattle hepatic drug metabolism, and further confirmed the presence of species differences in DME expression and activity between cattle, humans, and rodents. This reinforced the need for an extensive characterization and understanding of comparative molecular mechanisms involved in expression, regulation, and function of DMEs.

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Section: Discussionmentioning

confidence: 99%

Induction by Phenobarbital of Phase I and II Xenobiotic-Metabolizing Enzymes in Bovine Liver: An Overall Catalytic and Immunochemical Characterization

Cantiello

Carletti

Giantin

et al. 2022

IJMS

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“…The total or ultimate antioxidant capacity of a food is therefore a combined action of different antioxidants, through additive, synergistic, or antagonistic effects. ,, These interactions may also occur in the complex human environment, which are further complicated with other factors including interactions of food bioactives with drugs. This is an important area of research that warrants renewed efforts. , …”

Section: Phytochemical Antioxidantsmentioning

confidence: 99%

“…This is an important area of research that warrants renewed efforts. 61,62 ■ ANTI-INFLAMMATORY EFFECTS OF…”

Section: ■ Phytochemical Antioxidantsmentioning

confidence: 99%

Paradigm Shift in Phytochemicals Research: Evolution from Antioxidant Capacity to Anti-Inflammatory Effect and to Roles in Gut Health and Metabolic Syndrome

Liang

Sun

Tsao

2022

J. Agric. Food Chem.

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Food bioactive components, particularly phytochemicals with antioxidant capacity, have been extensively studied over the past two decades. However, as new analytical and molecular biological tools advance, antioxidants related research has undergone significant paradigm shifts. This review is a high-level overview of the evolution of phytochemical antioxidants research. Early research used chemical models to assess the antioxidant capacity of different phytochemicals, which provided important information about the health potential, but the results were overused and misinterpreted despite the lack of biological relevance (Antioxidants v1.0). This led to findings in the anti-inflammatory properties and modulatory effects of cell signaling of phytochemicals (Antioxidants v2.0). Recent advances in the role of diet in modulating gut microbiota have suggested a new phase of food bioactives research along the phytochemicals−gut microbiota−intestinal metabolites−low-grade inflammation−metabolic syndrome axis (Antioxidants v3.0). Polyphenols and carotenoids were discussed in-depth, and future research directions were also provided.

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“…Internalized anti-cancer drugs are metabolized by enzymes through phase I and phase II reactions. Phase I reactions include oxidation, reduction, and hydrolysis, which are mediated by cytochrome P450 enzymes (CYPs) and epoxide hydrolases [ 31 , 32 , 33 ]. Phase II reactions are conjugation reactions that include glucuronidation, sulfation, and glutathionylation.…”

Section: Multidrug Resistance In Cancer Chemotherapymentioning

confidence: 99%

Glycyrrhizin as a Nitric Oxide Regulator in Cancer Chemotherapy

Kim

Park

Lee

2021

Cancers

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Chemotherapy is used widely for cancer treatment; however, the evolution of multidrug resistance (MDR) in many patients limits the therapeutic benefits of chemotherapy. It is important to overcome MDR for enhanced chemotherapy. ATP-dependent efflux of drugs out of cells is the main mechanism of MDR. Recent studies have suggested that nitric oxide (NO) can be used to overcome MDR by inhibiting the ATPase function of ATP-dependent pumps. Several attempts have been made to deliver NO to the tumor microenvironment (TME), however there are limitations in delivery. Glycyrrhizin (GL), an active compound of licorice, has been reported to both reduce the MDR effect by inhibiting ATP-dependent pumps and function as a regulator of NO production in the TME. In this review, we describe the potential role of GL as an NO regulator and MDR inhibitor that efficiently reduces the MDR effect in cancer chemotherapy.

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Phytochemical and Over-The-Counter Drug Interactions: Involvement of Phase I and II Drug-Metabolizing Enzymes and Phase III Transporters

Cited by 7 publications

References 172 publications

Induction by Phenobarbital of Phase I and II Xenobiotic-Metabolizing Enzymes in Bovine Liver: An Overall Catalytic and Immunochemical Characterization

Induction by Phenobarbital of Phase I and II Xenobiotic-Metabolizing Enzymes in Bovine Liver: An Overall Catalytic and Immunochemical Characterization

Paradigm Shift in Phytochemicals Research: Evolution from Antioxidant Capacity to Anti-Inflammatory Effect and to Roles in Gut Health and Metabolic Syndrome

Glycyrrhizin as a Nitric Oxide Regulator in Cancer Chemotherapy

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