title: Hesperidin metabolite hesperetin-7-O-glucuronide, but not hesperetin-3'-O-glucuronide, exerts hypotensive, vasodilatory, and anti-inflammatory activities.
abstract: Orally ingested hesperidin (HES) is hydrolyzed into hesperetin in the gastrointestinal tract and conjugated during absorption. Hesperetin conjugates are the main circulating metabolites in human and rat plasma. We previously reported that glucosyl hesperidin (GHES), a water-soluble HES derivative, prevents hypertension via improvement of endothelial dysfunction in spontaneously hypertensive rats (SHRs). Although these hesperetin conjugates seem to be responsible for hypotensive and endothelium-dependent vasodilatory activities of dietary GHES, little is known about the mechanisms of action of these conjugated metabolites. Therefore, the aim of the present study was to investigate the effects of hesperetin-7-O-β-d-glucuronide (HPT7G) and hesperetin-3'-O-β-d-glucuronide (HPT3'G), which are the predominant HES metabolites in rat plasma, on blood pressure and endothelial function. Intravenous administration of HPT7G (5 mg kg(-1)) decreased blood pressure in anesthetized SHRs. HPT7G enhanced endothelium-dependent vasodilation in response to acetylcholine, but had no effect on endothelium-independent vasodilation in response to sodium nitroprusside (SNP) in aortas isolated from SHRs. HPT7G decreased hydrogen peroxide-induced intracellular adhesion molecule-1 and monocyte chemoattractant protein-1 mRNA expression in rat aortic endothelial cells. In contrast, HPT3'G had little effect on these parameters. In conclusion, HPT7G exerted hypotensive, vasodilatory and anti-inflammatory activities, similar to hesperetin and these effects are associated, in part, with the activity of GHES and HES to improve hypertension and endothelial dysfunction.
authors.affiliation: Biological Science Laboratories, Kao Corporation, 2606 Akabane Ichikai-machi, Haga-Gun Tochigi 321-3497, Japan. yamamoto.masaki@kao.co.jp
authors.forename: Masaki
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Hiroko
authors.initials: H
authors.lastname: Jokura
authors.forename: Koujiro
authors.initials: K
authors.lastname: Hashizume
authors.forename: Hideo
authors.initials: H
authors.lastname: Ominami
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Shibuya
authors.forename: Atsushi
authors.initials: A
authors.lastname: Suzuki
authors.forename: Tadashi
authors.initials: T
authors.lastname: Hase
authors.forename: Akira
authors.initials: A
authors.lastname: Shimotoyodome
mesh_terms: D000109:Acetylcholine; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005960:Glucosides / Q000494:pharmacology; D020719:Glucuronides / Q000494:pharmacology; D006569:Hesperidin / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D000959:Antihypertensive Agents; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D005960:Glucosides; D020719:Glucuronides; D012333:RNA, Messenger; D014665:Vasodilator Agents; C587870:hesperetin-7-O-glucuronide; D018799:Intercellular Adhesion Molecule-1; C487382:glucosyl hesperidin; D006861:Hydrogen Peroxide; D006569:Hesperidin; D000109:Acetylcholine