Administration of Piceatannol Complexed with α-Cyclodextrin Improves Its Absorption in Rats.

Piceatannol is polyphenolic antioxidant found in passion fruit (Passiflora edulis) seeds. The aim of this study was to improve the absorption of piceatannol using α-cyclodextrin (αCD). The solubility of piceatannol in neutral and acidic solutions increased in an αCD concentration-dependent manner. The maximum plasma concentration of intact piceatannol and the time-to-maximum plasma concentration of O-methylated piceatannol metabolites increased in rats administered αCD-piceatannol inclusion complexes (PICs). Administering the αCD inclusion complexes significantly increased the area under the concentration-time curve of total stilbene derivatives (0-3 h) in terms of the total amount of intact piceatannol, O-methylated piceatannol, conjugated piceatannol, and isorhapontigenin. Gastrointestinal ligation experiments demonstrated that substantially higher levels of piceatannol metabolites were present in the lower intestine (the ileum) at 1 h postintragastric αCD-PICs administration as compared to those observed following piceatannol administration only. These results suggested that αCD enhanced piceatannol movement and absorption in the small intestine.

Enhanced glucose tolerance by intravascularly administered piceatannol in freely moving healthy rats.

Piceatannol is a phytochemical in the seeds of passion fruit that has a hypoglycemic effect when orally administered. To elucidate the contribution of intact and metabolites of piceatannol after gastro-intestinal absorption to hypoglycemic effect, we examined the influence of piceatannol and isorhapontigenin on blood glucose concentrations during fasting and glucose tolerance tests by administering them intravascularly to freely moving healthy rats. We found that intravascularly administered piceatannol reduced the blood glucose concentrations during both fasting and glucose tolerance tests, but isorhapontigenin did not during either of them. Furthermore, we found that piceatannol increased the insulinogenic index during glucose tolerance tests and that piceatannol had no influence on insulin sensitivity by performing hyperinsulinemic euglycemic clamping tests. These results suggest that piceatannol orally intaken may enhance glucose tolerance by the effect of intact piceatannol through enhanced early-phase secretion of insulin. Therefore, oral intake of piceatannol might contribute to proper control of postprandial glycemic excursions in healthy subjects.

Absorption and metabolism of piceatannol in rats.

Piceatannol (trans-3,3',4,5'-tetrahydroxystilbene), a natural analogue of resveratrol, has multiple biological functions. Nevertheless, piceatannol's biological fate is yet to be determined. In this study, we evaluated the absorption and metabolism of piceatannol in rats. Furthermore, the area under the plasma concentration curves (AUC) and metabolic pathway of piceatannol were compared with those of resveratrol. We determined the plasma concentrations of piceatannol, resveratrol, and their respective metabolites following their intragastric administration. Resveratrol metabolites were only conjugates, whereas piceatannol metabolites were piceatannol conjugates, O-methyl piceatannol, and its conjugates. The AUC for piceatannol, resveratrol, and their metabolites increased in a dose-dependent manner (90-360 µmol/kg). The AUC for total piceatannol was less than that for total resveratrol, whereas the AUC for piceatannol (8.6 µmol·h/L) after piceatannol and resveratrol coadministration was 2.1 times greater than that for resveratrol (4.1 µmol·h/L). The greater AUC for piceatannol was a result of its higher metabolic stability.

Comparison of (-)-epigallocatechin-3-O-gallate (EGCG) and O-methyl EGCG bioavailability in rats.

(-)-Epigallocatechin-3-O-(3-O-methyl)gallate (EGCG3″Me) and (-)-epigallocatechin-3-O-(4-O-methyl)gallate (EGCG4″Me) are O-methyl derivatives of (-)-epigallocatechin-3-O-gallate (EGCG) present in tea cultivars such as Benifuuki. Although O-methyl EGCGs have various bioactivities, their bioavailabilities have not been determined. In this study, we compared the bioavailability of EGCG and O-methyl EGCGs in rats, and clarified the pharmacokinetics of O-methyl EGCGs. Following oral administration (100 mg/kg), the areas under the concentration-time curves (AUCs) for EGCG, EGCG3″Me, and EGCG4″Me were 39.6 ± 14.2 µg·h/L, 317.2 ± 43.7 µg·h/L, and 51.9 ± 11.0 µg·h/L, respectively. The AUC after intravenous administration (10 mg/kg) was 2772 ± 480 µg·h/L for EGCG, 8209 ± 549 µg·h/L for EGCG3″Me, and 2465 ± 262 µg·h/L for EGCG4″Me. The bioavailability of EGCG3″Me (0.38%) was the highest (EGCG: 0.14% and EGCG4″Me: 0.21%). The distribution volume of EGCG3″Me (0.26 ± 0.02 L/kg) was the lowest (EGCG: 0.94 ± 0.16 L/kg and EGCG4″Me: 0.93 ± 0.14 L/kg). These results suggested that the higher AUC of EGCG3″Me after oral administration was related to its high bioavailability and low distribution volume. These findings supported the stronger bioactivity of EGCG3″Me in vivo.