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

Abstract

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): þ 7·0 % in OVX rats treated with Hp (HpOVX) and þ 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.Bioavailability: Bone mineral density: Hesperidin: Flavanones: Rats Nutrition plays an important role in the dietary management and prevention of osteoporosis, a major public health problem. While it is established that Ca, vitamin D and micronutrients are essential for bone health, other compounds such as polyphenols, found abundantly in fruit and vegetables, show potential for bone-protective effects. For example, rodent studies have shown that quercetin and quercetin-3-rhamnoglucoside (rutin) from onions (1,2) , resveratrol from red wine (3) and isoflavones from soya (4) inhibit ovariectomised (OVX)-induced bone loss. Until now, most of the human intervention studies have been carried out with high levels of soya isoflavones (80-90 mg), some studies showing prevention of bone loss in postmenopausal women (5,6) , while others not (7,8) . The level of consumption of soya products is rather low in Western countries compared with Asian ones, whose daily intakes average 20 -40 mg (9) . Therefore, it would be of interest to identify commonly consumed polyphenols with bone-protective effects, as soya is not used as a staple in the Western diet.Hesperidin (Hp), a monomethoxylated flavanone found abundantly in citrus fruits such as oranges (10) , is highly consumed in Western countries. Indeed, in Finland, Hp consumption was estimated to be 28 mg/d, contributing to 50 % of total flavonoid intake (11) . Hp and metabolites show promising health benefit...

Enzymatic bioconversion of citrus hesperidin by Aspergillus sojae naringinase: Enhanced solubility of hesperetin-7-O-glucoside with in vitro inhibition of human intestinal maltase, HMG-CoA reductase, and growth of Helicobacter pylori

“…Hes-7-G and hesperetin aglycone, produced by the hydrolysis of enzymatic treatments, are better absorbed from the small intestine compared to hesperidin glycoside with rhamnose (Nielsen et al, 2006). The bioavailability of the flavonoid has been demonstrated to increase when hesperidin is enzymatically transformed into Hes-7-G (Bredsdorff et al, 2010;Day et al, 2000;Habauzit et al, 2009;Manach, Morand, Gil-Izquierdo, BouteloupDemange, & Rémésy, 2003;Németh et al, 2003). However, it is not clearly explained why Hes-7-G is more bioavailable than native hesperidin.…”

Evaluation of the inhibition of mushroom tyrosinase and cellular tyrosinase activities of oxyresveratrol: comparison with mulberroside A

“…Flavonoids generally occur as glycosides; removal of the glycone results in the enhancement of antioxidant, anticancer, and antimicrobial activity, and bone-loss prevention functions [4][5][6] . Many anticancer agents are activated by enzyme catalysis 7 .…”

Biotransformation of mulberroside A from Morus alba results in enhancement of tyrosinase inhibition

“…Biotransformation has been conducted to improve bioavailability of flavonoids [7,8,23]. Flavonoids generally contain glycosides; however, flavonoids with glycosides removed have shown improved antioxidant, anticancer, and antimicrobial activities and have also more effectively prevented bone loss.…”