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Y. Iwase, Y. Takemura, M. Ju-Ichi, M. Yano, C. Ito, H. Furukawa, T. Mukainaka, M. Kuchide, H. Tokuda and H. Nishino, “Cancer Chemopreventive Activity of 3,5,6,7,8,3’,4’-Heptamethoxyflavone from the Peel of Citrus Plants,” Cancer Letters, Vol. 163, No. 1, 2001, pp. 7-9. doi:10.1016/S0304-3835(00)00691-1

has been cited by the following article:

• TITLE: Protective Effects of Nobiletin on Hypertension and Cerebral Thrombosis in Stroke-Prone Spontaneously Hypertensive Rats (SHRSP)

  AUTHORS: Miyako Ikemura, Yasuto Sasaki, John C. Giddings, Junichiro Yamamoto

  KEYWORDS: Nitric Oxide (NO); Nobiletin; Reactive Oxygen Species (ROS); Stroke-Prone Spontaneously Hypertensive Rat (SHRSP); Thrombosis

  JOURNAL NAME: Food and Nutrition Sciences, Vol.3 No.11, November 20, 2012

  ABSTRACT: Some citrus flavonoids have been reported to possess antioxidant activities that moderate endothelial dysfunction and show protective effects on cardiovascular disease. We have investigated the protective effects of nobiletin (5,6,7,8,3’,4’-hexamethoxy flavone) derived from the peel of Citrus depressa Hayata (Shiikuwasha), a citrus fruit produced in Okinawa prefecture in Japan on hypertension and thrombogenicity in cerebral vessels of stroke-prone spontaneously hypertensive rats (SHRSP). Nobiletin was added to the diet of male SHRSP (7 weeks old) for 4 weeks. The age-related increase in systolic blood pressure usually observed in SHRSP was significantly suppressed in the treated animals. Thrombogenesis in pial blood vessels, determined using a He-Ne laser technique, and antioxidant activity, assessed by measuring urinary 8-hydroxy-2’-deoxyguanosine (8-OHdG), were significantly reduced after treatment. Urinary nitric oxide (NO) metabolites and acetylcholine-induced endothelial relaxation were increased after dietary intervention. These results strongly suggested that antihypertensive and antithrombotic effects of nobiletin may be related to an increase in bioavailable NO, possibly mediated by the scavenging of reactive oxygen species (ROS).