Regioselective Glucuronidation of Oxyresveratrol, a Natural Hydroxystilbene, by Human Liver and Intestinal Microsomes and Recombinant UGTs

Hu, Nan; Mei, Mei; Ruan, Jianqing; Wu, Wenjin; Wang, Ying; Yan, Ru

doi:10.2133/dmpk.dmpk-13-rg-102

Cited by 10 publications

(11 citation statements)

References 30 publications

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“…However, this compound poses a challenge for development into a phytopharmaceutical product due to its poor pharmacokinetic profile. This problem is a common phenomenon of lead compounds from natural resources, especially low oral bioavailability due to extensive metabolism in the gastrointestinal tract [11, 14, 24]. The goal of this study was to determine whether the pharmacokinetic profile of oxyresveratrol could be improved by combination with piperine, which acts as a bioenhancer in rats.…”

Section: Discussionmentioning

confidence: 99%

Comparative pharmacokinetics of oxyresveratrol alone and in combination with piperine as a bioenhancer in rats

Junsaeng

Anukunwithaya

Songvut

et al. 2019

BMC Complement Altern Med

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Background Oxyresveratrol is a major bioactive component derived from the heartwood of Artocarpus lacucha . This compound exerts several biological activities, including neuroprotective effects in vitro and in vivo. However, there is limited pharmacokinetic information on this compound, especially its distribution in neuronal tissue and its route of excretion. The aim of this study was to investigate the pharmacokinetic profiles of oxyresveratrol alone and in combination with piperine as a bioenhancer in rats. Methods Male Wistar rats were administered with oxyresveratrol 10 mg/kg, oxyresveratrol 10 mg/kg plus piperine 1 mg/kg via intravenous or oxyresveratrol 100 mg/kg, oxyresveratrol 100 mg/kg plus piperine 10 mg/kg via oral gavage. Plasma, internal organs, urine, and feces were collected. Determination of the oxyresveratrol concentration in biological samples was performed by liquid chromatography tandem mass spectrometry. Results The combination with piperine had shown a significantly higher maximum concentration in plasma approximately 1500 μg/L within 1–2 h after oral dosing, and could increase oral bioavailability of oxyresveratrol approximately 2–fold. Oxyresveratrol could widely distributed most of the internal organs with a tissue to plasma ratio of 10–100 fold within 5 min after dosing. Urinary excretion of oxyresveratrol glucuronide was the major route of excretion after administration of oxyresveratrol alone and in combination with piperine. Conclusion The addition of piperine could enhance some of the pharmacokinetic properties of oxyresveratrol via both intravenous and oral administration. This pharmacokinetic information will be useful for appropriate strategies to develop oxyresveratrol as a phytopharmaceutical product. Electronic supplementary material The online version of this article (10.1186/s12906-019-2653-y) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Comparative pharmacokinetics of oxyresveratrol alone and in combination with piperine as a bioenhancer in rats

Junsaeng

Anukunwithaya

Songvut

et al. 2019

BMC Complement Altern Med

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“…ORV is then quickly absorbed and undergoes hepatic conjugation to provide ORV 2- O -β-D-glucuronide and ORV sulfate. A further study using human liver and intestinal microsomes revealed that 2- O -β-D-glucuronide is the major metabolite, and UDP-glucuronosyltransferases (UGTs) are the enzymes involved in the transformation [ 282 ].…”

Section: Pharmacokinetic Profilementioning

confidence: 99%

Oxyresveratrol: Sources, Productions, Biological Activities, Pharmacokinetics, and Delivery Systems

Likhitwitayawuid

2021

Molecules

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Oxyresveratrol has recently attracted much research attention due to its simple chemical structure and diverse therapeutic potentials. Previous reviews describe the chemistry and biological activities of this phytoalexin, but additional coverage and greater accessibility are still needed. The current review provides a more comprehensive summary, covering research from 1955 to the present year. Oxyresveratrol occurs in both gymnosperms and angiosperms. However, it has never been reported in plants in the subclass Sympetalae, and this point might be of both chemotaxonomic and biosynthetic importance. Oxyresveratrol can be easily obtained from plant materials by conventional methods, and several systems for both qualitative and quantitative analysis of oxyresveratrol contents in plant materials and plant products are available. Oxyresveratrol possesses diverse biological and pharmacological activities such as the inhibition of tyrosinase and melanogenesis, antioxidant and anti-inflammatory activities, and protective effects against neurological disorders and digestive ailments. However, the unfavorable pharmacokinetic properties of oxyresveratrol, including low water solubility and poor oral availability and stability, have posed challenges to its development as a useful therapeutic agent. Recently, several delivery systems have emerged, with promising outcomes that may improve chances for the clinical study of oxyresveratrol.

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“…However, the therapeutic effect of OXY administered via the oral route is limited due to its poor intestinal permeability and efflux pump transport involving P-glycoprotein and multidrug resistance proteins [14]. In addition, OXY undergoes first-pass metabolism and rapid elimination in both intestine and liver resulting in very low oral bioavailability [15][16]. The extensive metabolism of OXY leads to the formation of glucuronide and sulfate conjugates and subsequent loss of biological activity [17].…”

Section: A Self-microemulsifying Formulation Of Oxyresveratrol Prevenmentioning

confidence: 99%

A Self-Microemulsifying Formulation of Oxyresveratrol Prevents Amyloid Beta Protein-Induced Neurodegeneration in Mice

et al. 2018

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The polyphenol compound, oxyresveratrol (OXY) possesses potent antioxidant and neuroprotective properties of potential utility in the treatment of Alzheimer's disease. However, the low oral bioavailability limits its neuroprotective effect and clinical application. The neuroprotective effect of orally administered OXY-loaded self-microemulsifying drug delivery system (OXY-SMEDDS) was compared with free OXY . Mice were orally administered either free OXY or OXY-SMEDDS once daily at a dose of 90, 180, or 360 mg/kg for 14 d. Mice received a single intracerebroventricular injection of the neurotoxic amyloid (A) peptide at day 8 during oral treatment. The OXY-SMEDDS formulation resulted in four-times reduction of the free OXY dose required for prevention of neurotoxicity effects due to A peptide as demonstrated by a significant decline in behavior impairments, lipid oxidation levels, and neuronal cell loss in all hippocampal subfields (p < 0.0001). These results indicate the potential of OXY-SMEDDS by oral delivery to improve the efficacy of this compound in the treatment of Alzheimer's disease.

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Regioselective Glucuronidation of Oxyresveratrol, a Natural Hydroxystilbene, by Human Liver and Intestinal Microsomes and Recombinant UGTs

Cited by 10 publications

References 30 publications

Comparative pharmacokinetics of oxyresveratrol alone and in combination with piperine as a bioenhancer in rats

Comparative pharmacokinetics of oxyresveratrol alone and in combination with piperine as a bioenhancer in rats

Oxyresveratrol: Sources, Productions, Biological Activities, Pharmacokinetics, and Delivery Systems

A Self-Microemulsifying Formulation of Oxyresveratrol Prevents Amyloid Beta Protein-Induced Neurodegeneration in Mice

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