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).
Highlights
Citrus fruits are a rich source of flavanones and many polymethoxylated flavones, which are very rare in other plants [1]
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)
Our findings indicate that the antioxidant activities of these compounds prevented conversion of nitric oxide (NO) into peroxynitrite (ONOO−) and increased the levels bioavailable NO, mediating an increase in vasorelaxation and leading to a decrease in blood pressure
Summary
Citrus fruits are a rich source of flavanones and many polymethoxylated flavones, which are very rare in other plants [1]. Citrus flavonoids are generally categorized into two groups, flavanone glycosides (hesperidin, naringin and neohesperidin) and polymethoxylated flavones (nobiletin, tangeretin and sinensetin) [2]. They have a broad spectrum of biological activity, including antioxidant activities [2,3,4,5], anti-inflammatory [3,6,7], neuroprotective properties [8,9,10] and anticarcinogenic and antitumor activities [6,11,12,13].
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