3,4-Dihydroxyphenethyl nitrate with nitric oxide releasing,antioxidant, hypoglycemic and hypolipidemic effects |
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| Affiliation: | 1. Laboratory of Toxicological Genetics, Lutheran University of Brazil (ULBRA), Farroupilha Avenue, 8001, CEP 92425-900 Canoas, RS, Brazil;2. Laboratory of Neuropharmacology and Preclinical Toxicology, Federal University of Rio Grande do Sul (UFRGS), Sarmento Leite Street, 500/305, CEP 90050-170 Porto Alegre, RS, Brazil;3. Laboratory of Clinical Pathology, Veterinary Hospital, Lutheran University of Brazil (ULBRA), Farroupilha Avenue, 8001, CEP 92425-900 Canoas, RS, Brazil;4. Laboratory of Oxidative Stress and Antioxidants, Lutheran University of Brazil (ULBRA), Farroupilha Avenue, 8001, CEP 92425-900 Canoas, RS, Brazil;5. Laboratory of Pharmacognosis and Phytochemistry, Lutheran University of Brazil (ULBRA), Farroupilha Avenue, 8001, CEP 92425-900 Canoas, RS, Brazil |
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| Abstract: | ![]()
Nitric oxide (NO) dysfunction, oxidative stress, and dyslipidemia are main risk factors associated with the pathophysiology of diabetic complications. In this study, 3,4-dihydroxyphenethyl nitrate (HT-ONO2) was designed, synthesized and evaluated, which incorporated hydroxytyrosol (HT) and nitrate. HT-ONO2 significantly exhibited hypoglycemic activity after oral administration to diabetic mice induced by streptozocin (STZ). HT-ONO2 also potently decreased plasma triglyceride (TG), total cholesterol (TC) in hyperlipidemia mice induced by Triton WR 1339. Meanwhile, HT-ONO2 displayed NO-releasing and antioxidant activity both in diabetic and hyperlipidemia mice and in vitro. Moreover, HT-ONO2 shown definite vasodilation and α-glucosidase inhibition activity in vitro. The results suggested that the hybrid hydroxytyrosol-based nitrate with NO supplement, antioxidant, hypoglycemia and hypolipidemia provided a potential multi-target agent to ameliorate the diabetes mellitus and its complications. |
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| Keywords: | 3,4-Dihydroxyphenethyl nitrate NO releasing Antioxidant Hypoglycemia Hypolipidemia Vasodilatation |
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