title: Apigenin and naringenin ameliorate PKCβII-associated endothelial dysfunction via regulating ROS/caspase-3 and NO pathway in endothelial cells exposed to high glucose.
abstract: Endothelial dysfunction is a key event in the progression of atherosclerosis with diabetes. Increasing cell apoptosis may lead to endothelial dysfunction. Apigenin and naringenin are two kinds of widely used flavones. In the present study, we investigated whether and how apigenin and naringenin reduced endothelial dysfunction induced by high glucose in endothelial cells. We showed that apigenin and naringenin protected against endothelial dysfunction via inhibiting phosphorylation of protein kinase C βII (PKCβII) expression and downstream reactive oxygen species (ROS) production in endothelial cells exposed to high glucose. Furthermore, we demonstrated that apigenin and naringenin reduced high glucose-increased apoptosis, Bax expression, caspase-3 activity and phosphorylation of NF-κB in endothelial cells. Moreover, apigenin and naringenin effectively restored high glucose-reduced Bcl-2 expression and Akt phosphorylation. Importantly, apigenin and naringenin significantly increased NO production in endothelial cells subjected to high glucose challenge. Consistently, high glucose stimulation impaired acetylcholine (ACh)-mediated vasodilation in the rat aorta, apigenin and naringenin treatment restored the impaired endothelium-dependent vasodilation via dramatically increasing eNOS activity and nitric oxide (NO) level. Taken together, our results manifest that apigenin and naringenin can ameliorate endothelial dysfunction via regulating ROS/caspase-3 and NO pathway.
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, PR China; Jiangsu Key Laboratory of TCM Evaluation and Translational Research, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, PR 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, Nanjing 211198, PR China; Taiyuan Institute For Food And Drug Control, 85 Longcheng Avenue, Taiyuan 030000, PR 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, Nanjing 211198, PR China; Jiangsu Key Laboratory of TCM Evaluation and Translational Research, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, PR 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, Nanjing 211198, PR China; Jiangsu Key Laboratory of TCM Evaluation and Translational Research, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, PR China.
authors.forename: Shujun
authors.initials: S
authors.lastname: Liang
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, PR China; Jiangsu Key Laboratory of TCM Evaluation and Translational Research, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, PR China.
authors.forename: Baiqiu
authors.initials: B
authors.lastname: He
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, PR China; Jiangsu Key Laboratory of TCM Evaluation and Translational Research, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, PR China.
authors.forename: Xiaoji
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, PR China; Jiangsu Key Laboratory of TCM Evaluation and Translational Research, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, PR China.
authors.forename: Liying
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, PR China.
authors.forename: Jingyu
authors.initials: J
authors.lastname: Liang
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, PR China; Jiangsu Key Laboratory of TCM Evaluation and Translational Research, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, PR China. Electronic address: fhwu2000@sina.com.
authors.forename: Feihua
authors.initials: F
authors.lastname: Wu
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology; D047310:Apigenin / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D044950:Flavanones / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D064546:Protein Kinase C beta / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects
chemical_list: D044950:Flavanones; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D047310:Apigenin; D052250:Nitric Oxide Synthase Type III; D064546:Protein Kinase C beta; D053148:Caspase 3; C005273:naringenin; D005947:Glucose
keywords: Acetylcholine (PubChem CID: 75271); Apigenin; Apigenin (PubChem CID: 5280443); Apoptosis; Endothelial dysfunction; High glucose; Naringenin; Naringenin (PubChem CID: 932); Phenylephrine (PubChem CID: 5284443)