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

Abstract

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.

Biotransformation of Piceatannol, a Dietary Resveratrol Derivative: Promises to Human Health

“…However, the brain distribution of PIC and its metabolites remain unclear although previous studies found that hydroxystilbenes including RES and OXY could penetrate through the bloodbrain barrier. [43][44][45] Moreover, our previous study confirmed that pterostilbene (trans-3,5-dimethoxy-4′-hydroxystilbene), the partially methylated RES displayed very abundant brain exposure. [8] As RHA and ISO also possess methoxy group, they might possess favorable brain distribution as well.…”

“…As a substrate inhibitor of COMT with moderate K i values (<15 µ m ), the concentration for PIC to suppress COMT appears to be achievable in human liver after single oral dosing. However, the brain distribution of PIC and its metabolites remain unclear although previous studies found that hydroxystilbenes including RES and OXY could penetrate through the blood–brain barrier . Moreover, our previous study confirmed that pterostilbene ( trans ‐3,5‐dimethoxy‐4′‐hydroxystilbene), the partially methylated RES displayed very abundant brain exposure .…”

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

“…A study of the effect of piperine on the pharmacokinetic profile of oral ORV was conducted [ 283 ]. The oral availability of ORV was enhanced twofold when given in a combination with piperine.…”

“…As mentioned earlier, a novel approach to improve the pharmacokinetic profile of ORV was studied in rats using piperine as the bioenhancer. The oral bioavailability of ORV was increased twofold when ORV was co-administered with piperine [ 283 ].…”

Glycosylation of Stilbene Compounds by Cultured Plant Cells

“…Oxyresveratrol (3,5,2 ,4 -tetrahydroxystilbene) and gnetol (3,5,2 ,6 -tetrahydroxystilbene) are the major bioactive stilbenoids. These compounds are contained in plants such as Artocarpus lacucha Buch.-Ham and Gnetum gnemon, which have been used as folk medicines [1]. They have many pharmacological activities such as anti-oxidant, anti-inflammatory, analgesic, antidiabetic, anti-adipogenesis, anticancer, antileukaemic, and antiviral effects [2][3][4][5][6][7][8][9][10][11][12][13][14][15].…”