Increased bioavailability of hesperetin-7-glucoside compared with hesperidin results in more efficient prevention of bone loss in adult ovariectomised rats

Hesperidin (Hp), a citrus flavonoid predominantly found in oranges, shows bone-sparing effects in ovariectomised (OVX) animals. In human subjects, the bioavailability of Hp can be improved by the removal of the rhamnose group to yield hesperetin-7-glucoside (H-7-glc). The aim of the present work was to test whether H-7-glc was more bioavailable and therefore more effective than Hp in the prevention of bone loss in the OVX rat. Adult 6-month-old female Wistar rats were sham operated or OVX, then pair fed for 90 d a casein-based diet supplemented or not with freeze-dried orange juice enriched with Hp or H-7-glc at two dose equivalents of the hesperetin aglycone (0-25 and 0-5%). In the rats fed 0-5%, a reduction in OVX-induced bone loss was observed regarding total bone mineral density (BMD): + 7.0% in OVX rats treated with Hp (HpOVX) and + 6.6% in OVX rats treated with H-7-glc (H-7-glcOVX) v. OVX controls (P<0.05). In the rats fed 0.25% hesperetin equivalents, the H-7-glcOVX group showed a 6-6% improvement in total femoral BMD v. the OVX controls (P<0.05), whereas the Hp diet had no effect at this dose. The BMD of rats fed 0.25% H-7-glc was equal to that of those given 0.5% Hp, but was not further increased at 0.5% H-7-glc. Plasma hesperetin levels and relative urinary excretion were significantly enhanced in the H-7-glc v. Hp groups, and the metabolite profile showed the absence of eriodictyol metabolites and increased levels of hesperetin sulphates. Taken together, improved bioavailability of H-7-glc may explain the more efficient bone protection of this compound.