Interplay between metabolism and transport of resveratrol

Maier‐Salamon, Alexandra; Böhmdorfer, Michaela; Riha, Juliane; Thalhammer, Theresia; Szekeres, Thomas; Jaeger, Walter

doi:10.1111/nyas.12198

Cited by 46 publications

(33 citation statements)

References 31 publications

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“…Second, UDCA is an inducer of metabolizing enzymes in the gut and the liver (Hempfling et al, 2003). This is particularly important regarding RSV concerning the fact that RSV is extensively metabolized in the gut and the liver (Maier-Salamon et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Protective effect of ursodeoxycholic acid, resveratrol, andN-acetylcysteine on nonalcoholic fatty liver disease in rats

Ali

Messiha

Abdellatif

2015

Pharmaceutical Biology

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(2016) Protective effect of ursodeoxycholic acid, resveratrol, and Nacetylcysteine on nonalcoholic fatty liver disease in rats, Pharmaceutical Biology, 54:7, 1198-1208, DOI: 10.3109/13880209.2015 -a), glucose, albumin, renal functions (urea, creatinine), lipid profile (total cholesterol; TC, triglycerides, high density lipoproteins, low density lipoproteins; LDL-C, very low density lipoproteins, leptin), and oxidative stress markers (hepatic malondialdehyde; MDA, glutathione; GSH, glutathione-S-transferase; GST) were measured using automatic analyzer, colorimetric kits, and ELISA kits, supported by a liver histopathological study.Results: RSV and NAC administration significantly improved liver index (RSV only), alanine transaminase (52, 52%), TNF-a (70, 70%), glucose (69, 80%), albumin (122, 114%), MDA (55, 63%), GSH (160, 152%), GST (84, 84%), TC (86, 86%), LDL-C (83, 81%), and leptin (59, 70%) levels compared with steatosis control values. A combination of RSV or NAC with UDCA seems to ameliorate their effects. Discussion and conclusion: RSV and NAC are effective on NAFLD through antioxidant, antiinflammatory, and lipid-lowering potentials, where as RSV seems better than UDCA or NAC.

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Section: Discussionmentioning

confidence: 99%

Protective effect of ursodeoxycholic acid, resveratrol, andN-acetylcysteine on nonalcoholic fatty liver disease in rats

Ali

Messiha

Abdellatif

2015

Pharmaceutical Biology

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“…Indeed, the modifications just mentioned have been long recognized and studied for representative members of this huge family of natural compounds, including resveratrol, which is of specific interest here. Rapid glucuronidation and sulfation in enterocytes, hepatocytes, and other cells (e.g., [14][15][16][17][18][19][20][21]) and re-export to the intestinal lumen by MDR proteins [15,22,23], or possibly OATPs [24], are thought to limit the potential impact of this celebrated "natural drug" in vivo. This is a pity, given the pleiotropic effects this dietary compound is reported to have in important pathophysiological respects (for recent reviews see, e.g., [25][26][27][28][29][30]).…”

Section: Introductionmentioning

confidence: 99%

N-Monosubstituted Methoxy-oligo(ethylene glycol) Carbamate Ester Prodrugs of Resveratrol

et al. 2015

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Abstract:Resveratrol is a natural polyphenol with many interesting biological activities. Its pharmacological exploitation in vivo is, however, hindered by its rapid elimination via phase II conjugative metabolism at the intestinal and, most importantly, hepatic levels. One approach to bypass this problem relies on prodrugs. We report here the synthesis, characterization, hydrolysis, and in vivo pharmacokinetic behavior of resveratrol prodrugs in which the OH groups are engaged in an N-monosubstituted carbamate ester linkage. As promoiety, methoxy-oligo(ethylene glycol) groups (m-OEG) (CH3-[OCH2CH2]n-) of defined chain length (n = 3, 4, 6) were used. These are expected to modulate the chemico-physical properties of the resulting derivatives, much like longer poly(ethylene glycol) (PEG) chains, while retaining a relatively low MW and, thus, a favorable drug loading capacity. Intragastric administration to rats resulted in the appearance in the bloodstream of the prodrug and of the products of its partial hydrolysis, confirming protection from first-pass metabolism during absorption.

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“…XMEs as well as drug transporters share common regulatory pathways; for example, pregnane X receptor, constitutive androstane receptor, AhR/ARNT, and Nrf2-Keap mediated regulation of protein expression. Overlapping roles of metabolism and transport impact the overall disposition of RES and its conjugates (Maier-Salamon et al, 2013). It therefore becomes important to integrate metabolism and transport of RES across all eliminating organs to understand the target tissue concentrations of the active compound.…”

Section: Pulmonary Metabolism Of Resveratrol: In Vitro and In Vivomentioning

confidence: 99%

“Target-Site” Drug Metabolism and Transport

et al. 2015

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The recent symposium on "Target-Site" Drug Metabolism and Transport that was sponsored by the American Society for Pharmacology and Experimental Therapeutics at the 2014 Experimental Biology meeting in San Diego is summarized in this report. Emerging evidence has demonstrated that drug-metabolizing enzyme and transporter activity at the site of therapeutic action can affect the efficacy, safety, and metabolic properties of a given drug, with potential outcomes including altered dosing regimens, stricter exclusion criteria, or even the failure of a new chemical entity in clinical trials. Drug metabolism within the brain, for example, can contribute to metabolic activation of therapeutic drugs such as codeine as well as the elimination of potential neurotoxins in the brain. Similarly, the activity of oxidative and conjugative drug-metabolizing enzymes in the lung can have an effect on the efficacy of compounds such as resveratrol. In addition to metabolism, the active transport of compounds into or away from the site of action can also influence the outcome of a given therapeutic regimen or disease progression. For example, organic anion transporter 3 is involved in the initiation of pancreatic b-cell dysfunction and may have a role in how uremic toxins enter pancreatic b-cells and ultimately contribute to the pathogenesis of gestational diabetes. Finally, it is likely that a combination of target-specific metabolism and cellular internalization may have a significant role in determining the pharmacokinetics and efficacy of antibody-drug conjugates, a finding which has resulted in the development of a host of new analytical methods that are now used for characterizing the metabolism and disposition of antibody-drug conjugates. Taken together, the research summarized herein can provide for an increased understanding of potential barriers to drug efficacy and allow for a more rational approach for developing safe and effective therapeutics.

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Interplay between metabolism and transport of resveratrol

Cited by 46 publications

References 31 publications

Protective effect of ursodeoxycholic acid, resveratrol, andN-acetylcysteine on nonalcoholic fatty liver disease in rats

Protective effect of ursodeoxycholic acid, resveratrol, andN-acetylcysteine on nonalcoholic fatty liver disease in rats

N-Monosubstituted Methoxy-oligo(ethylene glycol) Carbamate Ester Prodrugs of Resveratrol

“Target-Site” Drug Metabolism and Transport

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