Abstract
Background: Isorhapontigenin (trans–3,5,4′-trihydroxy–3′–methoxystilbene, ISO), a dietary resveratrol (trans–3,5,4′–trihydroxystilbene) derivative, possesses various health-promoting activities. To further evaluate its medicinal potentials, the pharmacokinetic and metabolomic profiles of ISO were examined in Sprague-Dawley rats.Methods: The plasma pharmacokinetics and metabolomics were monitored by liquid chromatography–tandem mass spectrometry (LC–MS/MS) and gas chromatography–tandem mass spectrometry (GC–MS/MS), respectively.Results: Upon intravenous injection (90 μmol/kg), ISO exhibited a fairly rapid clearance (CL) and short mean residence time (MRT). After a single oral administration (100 μmol/kg), ISO was rapidly absorbed and showed a long residence in the systemic circulation. Dose escalation to 200 μmol/kg resulted in higher dose-normalized maximal plasma concentrations (Cmax/Dose), dose-normalized plasma exposures (AUC/Dose), and oral bioavailability (F). One-week repeated daily dosing of ISO did not alter its major oral pharmacokinetic parameters. Pharmacokinetic comparisons clearly indicated that ISO displayed pharmacokinetic profiles superior to resveratrol as its Cmax/Dose, AUC/Dose, and F were approximately two to three folds greater than resveratrol. Metabolomic investigation revealed that 1-week ISO administration significantly reduced plasma concentrations of arachidonic acid, cholesterol, fructose, allantoin, and cadaverine but increased tryptamine levels, indicating its impact on metabolic pathways related to health-promoting effects.Conclusion: ISO displayed favorable pharmacokinetic profiles and may be a promising nutraceutical in view of its health-promoting properties.
Highlights
IntroductionResveratrol (trans-3,4 ,5-trihydroxystilbene; Figure 1) is a phytoalexin present in a variety of fruits and plants such as grapevines, blueberry, and peanuts (Baur and Sinclair, 2006)
Resveratrol is a phytoalexin present in a variety of fruits and plants such as grapevines, blueberry, and peanuts (Baur and Sinclair, 2006)
The potency of ISO was much higher than resveratrol and its anti-inflammatory activities were mediated through a mechanistic pathway that is distinct from corticosteroids, which indicates its potential in tackling the corticosteroid-resistant inflammation in chronic obstructive pulmonary disease (COPD) (Yeo et al, 2017)
Summary
Resveratrol (trans-3,4 ,5-trihydroxystilbene; Figure 1) is a phytoalexin present in a variety of fruits and plants such as grapevines, blueberry, and peanuts (Baur and Sinclair, 2006). Its anti-cancer, anti-oxidation, and cardio-protective activities have been observed in various pre-clinical studies (Wang et al, 2001; Liu and Liu, 2004; Li et al, 2005; Fang et al, 2012, 2013; Zeng et al, 2016; Jiang et al, 2018). The antiinflammatory effects of ISO were assessed in in vitro models for chronic obstructive pulmonary disease (COPD) using resveratrol as a comparator (Yeo et al, 2017). The potency of ISO was much higher than resveratrol and its anti-inflammatory activities were mediated through a mechanistic pathway that is distinct from corticosteroids, which indicates its potential in tackling the corticosteroid-resistant inflammation in COPD (Yeo et al, 2017). To further evaluate its medicinal potentials, the pharmacokinetic and metabolomic profiles of ISO were examined in Sprague-Dawley rats
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
