Pharmacokinetics, oral bioavailability, and metabolic profile of resveratrol and its dimethylether analog, pterostilbene, in rats - PubMed (original) (raw)
Pharmacokinetics, oral bioavailability, and metabolic profile of resveratrol and its dimethylether analog, pterostilbene, in rats
Izet M Kapetanovic et al. Cancer Chemother Pharmacol. 2011 Sep.
Abstract
Purpose: Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a naturally occurring polyphenol with a broad range of possible health benefits, including anti-cancer activity. However, the biological activity of resveratrol may be limited by poor absorption and first-pass metabolism: only low plasma concentrations of resveratrol are seen following oral administration, and metabolism to glucuronide and sulfate conjugates is rapid. Methylated polyphenol analogs (such as pterostilbene [3,5-dimethoxy-4'-hydroxy-trans-stilbene], the dimethylether analog of resveratrol) may overcome these limitations to pharmacologic efficacy. The present study was designed to compare the bioavailability, pharmacokinetics, and metabolism of resveratrol and pterostilbene following equimolar oral dosing in rats.
Methods: The agents were administered orally via gavage for 14 consecutive days at 50 or 150 mg/kg/day for resveratrol and 56 or 168 mg/kg/day for pterostilbene. Two additional groups were dosed once intravenously with 10 and 11.2 mg/kg for resveratrol and pterostilbene, respectively. Plasma concentrations of agents and metabolites were measured using a high-pressure liquid chromatograph-tandem mass spectrometer system. Noncompartmental analysis was used to derive pharmacokinetic parameters.
Results: Resveratrol and pterostilbene were approximately 20 and 80% bioavailable, respectively. Following oral dosing, plasma levels of pterostilbene and pterostilbene sulfate were markedly greater than were plasma levels of resveratrol and resveratrol sulfate. Although plasma levels of resveratrol glucuronide exceeded those of pterostilbene glucuronide, those differences were smaller than those of the parent drugs and sulfate metabolites.
Conclusions: When administered orally, pterostilbene demonstrates greater bioavailability and total plasma levels of both the parent compound and metabolites than does resveratrol. These differences in agent pharmacokinetics suggest that the in vivo biological activity of equimolar doses of pterostilbene may be greater than that of resveratrol.
Figures
Fig. 1
Chemical structure of resveratrol (a) and pterostilbene (b)
Fig. 2
Plasma concentration–time curves for resveratrol and pterostilbene. Animals were orally dosed daily for 14 days, and pharmacokinetic profiles were obtained after the last dose. Symbols represent mean ± SD for n = 3
Similar articles
- Metabolism and pharmacokinetics of resveratrol and pterostilbene.
Wang P, Sang S. Wang P, et al. Biofactors. 2018 Jan;44(1):16-25. doi: 10.1002/biof.1410. Epub 2018 Jan 8. Biofactors. 2018. PMID: 29315886 Review. - Determination of resveratrol and its sulfate and glucuronide metabolites in plasma by LC-MS/MS and their pharmacokinetics in dogs.
Muzzio M, Huang Z, Hu SC, Johnson WD, McCormick DL, Kapetanovic IM. Muzzio M, et al. J Pharm Biomed Anal. 2012 Feb 5;59:201-8. doi: 10.1016/j.jpba.2011.10.023. Epub 2011 Oct 25. J Pharm Biomed Anal. 2012. PMID: 22079044 Free PMC article. - Determination of pterostilbene in rat plasma by a simple HPLC-UV method and its application in pre-clinical pharmacokinetic study.
Lin HS, Yue BD, Ho PC. Lin HS, et al. Biomed Chromatogr. 2009 Dec;23(12):1308-15. doi: 10.1002/bmc.1254. Biomed Chromatogr. 2009. PMID: 19488981 - Oral delivery system enhanced the bioavailability of stilbenes: Resveratrol and pterostilbene.
Peng RM, Lin GR, Ting Y, Hu JY. Peng RM, et al. Biofactors. 2018 Jan;44(1):5-15. doi: 10.1002/biof.1405. Epub 2018 Jan 11. Biofactors. 2018. PMID: 29322567 Review.
Cited by
- Dietary supplementation with pterostilbene activates the PI3K-AKT-mTOR signalling pathway to alleviate progressive oxidative stress and promote placental nutrient transport.
Cao M, Bai L, Wei H, Guo Y, Sun G, Sun H, Shi B. Cao M, et al. J Anim Sci Biotechnol. 2024 Oct 6;15(1):133. doi: 10.1186/s40104-024-01090-9. J Anim Sci Biotechnol. 2024. PMID: 39369257 Free PMC article. - The Aryl Hydrocarbon Receptor and Its Crosstalk: A Chemopreventive Target of Naturally Occurring and Modified Phytochemicals.
Szaefer H, Licznerska B, Baer-Dubowska W. Szaefer H, et al. Molecules. 2024 Sep 10;29(18):4283. doi: 10.3390/molecules29184283. Molecules. 2024. PMID: 39339278 Free PMC article. Review. - Pterostilbene, a Dimethyl Derivative of Resveratrol, Exerts Cytotoxic Effects on Melanin-Producing Cells through Metabolic Activation by Tyrosinase.
Tanaka H, Nishimaki-Mogami T, Tamehiro N, Shibata N, Mandai H, Ito S, Wakamatsu K. Tanaka H, et al. Int J Mol Sci. 2024 Sep 17;25(18):9990. doi: 10.3390/ijms25189990. Int J Mol Sci. 2024. PMID: 39337478 Free PMC article. - Targeting Cancer Hallmarks Using Selected Food Bioactive Compounds: Potentials for Preventive and Therapeutic Strategies.
Talib WH, Abed I, Raad D, Alomari RK, Jamal A, Jabbar R, Alhasan EOA, Alshaeri HK, Alasmari MM, Law D. Talib WH, et al. Foods. 2024 Aug 26;13(17):2687. doi: 10.3390/foods13172687. Foods. 2024. PMID: 39272454 Free PMC article. Review. - Pterostilbene, a Resveratrol Derivative, Improves Ovary Function by Upregulating Antioxidant Defenses in the Aging Chickens via Increased SIRT1/Nrf2 Expression.
Wang X, Yuan Q, Xiao Y, Cai X, Yang Z, Zeng W, Mi Y, Zhang C. Wang X, et al. Antioxidants (Basel). 2024 Aug 1;13(8):935. doi: 10.3390/antiox13080935. Antioxidants (Basel). 2024. PMID: 39199181 Free PMC article.
References
- Abd El-Mohsen M, Bayele H, Kuhnle G, Gibson G, Debnam E, Kaila Srai S, Rice-Evans C, Spencer JP. Distribution of [3H]trans-resveratrol in rat tissues following oral administration. Br J Nutr. 2006;96:62–70. - PubMed
- Baur JA, Sinclair DA. Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov. 2006;5:493–506. - PubMed
- Bishayee A. Cancer prevention and treatment with resveratrol: from rodent studies to clinical trials. Cancer Prev Res. 2009;2:409–418. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical