title: Quercetin glucosides promote ischemia-induced angiogenesis, but do not promote tumor growth.
abstract: OBJECTIVE
  Dietary flavonoid intake shows a significant inverse association with mortality from coronary heart disease, incidence of myocardial infarction and stroke. Quercetin is one of the most common flavonoids in our diet and has several favorable biological activities. Quercetin glucosides, which are enzymatically trans-glycosylated isoquercitrin, have high water-solubility and bioavailability compared with quercetin. Here, we investigated the effects of quercetin glucosides on collateral development in a murine hindlimb ischemia model.
  
  
  METHODS
  We induced hindlimb ischemia in 24- to 32-week-old male C3H/HeJ mice by resecting the right femoral artery. Then, 0.5% carboxymethyl cellulose (control) or quercetin glucosides (100mg/kg/day) were administered daily by gavage. Blood flow was monitored weekly by laser Doppler imaging.
  
  
  RESULTS
  Recovery of blood flow to the ischemic leg was significantly enhanced by quercetin glucosides (blood flow ratio at 4 weeks: control, 0.57 ± 0.11; quercetin glucosides, 0.95 ± 0.10, p<0.05). Furthermore, anti-CD31 immunostaining revealed that quercetin glucosides increased capillary density in the ischemic muscle (control, 200 ± 24/mm(2); quercetin glucosides, 364 ± 41/mm(2), p<0.01). Quercetin glucosides did not promote tumor growth. The beneficial effect of quercetin glucosides was abrogated in eNOS-deficient mice.
  
  
  CONCLUSIONS
  These results suggest that quercetin glucosides may have therapeutic potential to promote angiogenesis in ischemic tissue.
authors.affiliation: Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan; Department of Surgery, Jikei University School of Medicine, Tokyo 105-8471, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Sumi
authors.forename: Norifumi
authors.initials: N
authors.lastname: Tateishi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shibata
authors.forename: Takao
authors.initials: T
authors.lastname: Ohki
authors.forename: Masataka
authors.initials: M
authors.lastname: Sata
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002196:Capillaries / Q000503:physiopathology; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D005960:Glucosides / Q000737:chemistry / Q000494:pharmacology*; D006614:Hindlimb / Q000098:blood supply / Q000187:drug effects; D007511:Ischemia / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009369:Neoplasms / Q000139:chemically induced; D009389:Neovascularization, Pathologic / Q000139:chemically induced; D018919:Neovascularization, Physiologic / Q000187:drug effects; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D011794:Quercetin / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D043925:Angiogenesis Inducing Agents; D000975:Antioxidants; D016207:Cytokines; D005960:Glucosides; C016527:isoquercitrin; D011794:Quercetin; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse
keywords: Angiogenesis; Collateral; Flavonoids; NO; Quercetin glucosides