title: Apigenin and naringenin regulate glucose and lipid metabolism, and ameliorate vascular dysfunction in type 2 diabetic rats.
abstract: Vascular endothelial dysfunction is regarded as the initial step of vascular complications in diabetes mellitus. This study investigated the amelioration of apigenin and naringenin in type 2 diabetic (T2D) rats induced by high-fat diet and streptozotocin and explored the underlying mechanism. Apigenin or naringenin was intragastrically administered at 50 or 100mg/kg once a day for 6 weeks. Biochemical parameters including blood glucose, glycated serum protein, serum lipid, insulin, superoxide dismutase (SOD), malonaldehyde and intercellular adhesion molecule-1 (ICAM-1) were measured. Vascular reactivity in isolated thoracic aortic rings was examined. Pathological features of the thoracic aorta were further observed through optical microscopy and transmission electron microscopy. Lastly, we evaluated their effects on insulin resistance of palmitic acid (PA)-induced endothelial cells. Compared with diabetic control group, apigenin and naringenin significantly decreased the levels of blood glucose, serum lipid, malonaldehyde, ICAM-1 and insulin resistance index, increased SOD activity and improved impaired glucose tolerance. Apigenin and naringenin restored phenylephrine-mediated contractions and acetylcholine or insulin-induced relaxations in aortic tissues. Furthermore, pathological damage in the thoracic aorta of apigenin and naringenin groups was more remissive than diabetic control group. In vitro, apigenin and naringenin inhibited NF-κB activation and ICAM-1 mRNA expression in PA-treated endothelial cells and improved nitric oxide production in the presence of insulin. In conclusion, both apigenin and naringenin can ameliorate glucose and lipid metabolism, as well as endothelial dysfunction in T2D rats at least in part by down-regulating oxidative stress and inflammation. In general, apigenin showed greater potency than naringenin equivalent.
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 639 Longmian Avenue, Jiangning District, Nanjing 211198, Jiangsu, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Ren
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 639 Longmian Avenue, Jiangning District, Nanjing 211198, Jiangsu, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Qin
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 639 Longmian Avenue, Jiangning District, Nanjing 211198, Jiangsu, China. Electronic address: fhwu2000@sina.com.
authors.forename: Feihua
authors.initials: F
authors.lastname: Wu
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 639 Longmian Avenue, Jiangning District, Nanjing 211198, Jiangsu, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 639 Longmian Avenue, Jiangning District, Nanjing 211198, Jiangsu, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Pan
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 639 Longmian Avenue, Jiangning District, Nanjing 211198, Jiangsu, China.
authors.forename: Liying
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, 639 Longmian Avenue, Jiangning District, Nanjing 211198, Jiangsu, China.
authors.forename: Biao
authors.initials: B
authors.lastname: Zeng
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 639 Longmian Avenue, Jiangning District, Nanjing 211198, Jiangsu, China.
authors.forename: Shiping
authors.initials: S
authors.lastname: Ma
authors.affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, 639 Longmian Avenue, Jiangning District, Nanjing 211198, Jiangsu, China.
authors.forename: Jingyu
authors.initials: J
authors.lastname: Liang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000503:physiopathology*; D047310:Apigenin / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology; D005215:Fasting / Q000097:blood; D044950:Flavanones / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D050356:Lipid Metabolism / Q000187:drug effects*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D010656:Phenylephrine / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D001786:Blood Glucose; D044950:Flavanones; D016328:NF-kappa B; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D010656:Phenylephrine; D009569:Nitric Oxide; D047310:Apigenin; C005273:naringenin
keywords: Acetylcholine (PubChem CID: 75271); Apigenin; Apigenin (PubChem CID: 5280443); Insulin (PubChem CID: 70678557); Metformin (PubChem CID: 14219); Naringenin; Naringenin (PubChem CID: 932); Palmitic acid; Palmitic acid (PubChem CID: 985); Phenylephrine (PubChem CID: 5284443); Streptozotocin; Type 2 diabetic rats; Vascular dysfunction