Your browser doesn't support javascript.
loading
Puerarin-7-O-glucuronide, a water-soluble puerarin metabolite, prevents angiotensin II-induced cardiomyocyte hypertrophy by reducing oxidative stress.
Hou, Ning; Cai, Bin; Ou, Cai-Wen; Zhang, Zhen-Hui; Liu, Xia-Wen; Yuan, Mu; Zhao, Gan-Jian; Liu, Shi-Ming; Xiong, Long-Gen; Luo, Jian-Dong; Luo, Cheng-Feng; Chen, Min-Sheng.
Afiliação
  • Hou N; Department of Pharmacology, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, China.
  • Cai B; Changsha Central Hospital, 161 Shaoshannan Road, Changsha, 410018, China.
  • Ou CW; Department of Cardiology, Guangdong Provincial Center of Biomedical Engineering for Cardiovascular Disease, Zhujiang Hospital of Southern Medical University, 253 Gongye Avenue, Guangzhou, 510280, China.
  • Zhang ZH; Department of Cardiology, Guangzhou Institute of Cardiovascular Disease, The Second Affiliated Hospital of Guangzhou Medical University, 250 Changgangdong Road, Guangzhou, 510260, China.
  • Liu XW; Department of Pharmacology, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, China.
  • Yuan M; Department of Pharmacology, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, China.
  • Zhao GJ; Department of Cardiology, Guangzhou Institute of Cardiovascular Disease, The Second Affiliated Hospital of Guangzhou Medical University, 250 Changgangdong Road, Guangzhou, 510260, China.
  • Liu SM; Department of Cardiology, Guangzhou Institute of Cardiovascular Disease, The Second Affiliated Hospital of Guangzhou Medical University, 250 Changgangdong Road, Guangzhou, 510260, China.
  • Xiong LG; Department of Cardiology, Guangzhou Institute of Cardiovascular Disease, The Second Affiliated Hospital of Guangzhou Medical University, 250 Changgangdong Road, Guangzhou, 510260, China.
  • Luo JD; Department of Pharmacology, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, China.
  • Luo CF; Department of Cardiology, Guangzhou Institute of Cardiovascular Disease, The Second Affiliated Hospital of Guangzhou Medical University, 250 Changgangdong Road, Guangzhou, 510260, China. rocenphone@gzhmu.edu.cn.
  • Chen MS; Department of Cardiology, Guangdong Provincial Center of Biomedical Engineering for Cardiovascular Disease, Zhujiang Hospital of Southern Medical University, 253 Gongye Avenue, Guangzhou, 510280, China. gzminsheng@vip.163.com.
Naunyn Schmiedebergs Arch Pharmacol ; 390(5): 535-545, 2017 May.
Article em En | MEDLINE | ID: mdl-28210753
ABSTRACT
This study aimed to investigate the anti-oxidant and anti-hypertrophic effects of puerarin-7-O-glucuronide, a water-soluble puerarin metabolite. The anti-oxidant effects of puerarin-7-O-glucuronide were assessed by measurement of intracellular superoxide levels, total superoxide dismutase (SOD) activity, total anti-oxidant capacity, and glutathione (GSH)/glutathione disulfide (GSSG) ratio in cultured neonatal rat cardiomyocytes (NRCMs) stimulated with the xanthine oxidase (XO)/xanthine (X) system or angiotensin II. The activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and expression of NADPH oxidase subunits p22phox and p47phox were determined. The anti-hypertrophic effects of puerarin-7-O-glucuronide in angiotensin II-challenged NRCMs were characterized by changes in cell morphology and expression of hypertrophic genes. In the pharmacokinetic study, the plasma concentration of puerarin-7-O-glucuronide was determined by rapid resolution-liquid chromatography-tandem mass spectrometry (RR-LC-MS/MS). Puerarin-7-O-glucuronide prevented XO/X-induced increase in intracellular superoxide production and decreases in total SOD activity, GSH/GSSG ratio, and total anti-oxidant capacity. Puerarin-7-O-glucuronide also reversed angiotensin II-induced increases in intracellular superoxide production and NADPH oxidase activity and decreases in total SOD activity. These anti-oxidant effects of puerarin-7-O-glucuronide were accompanied by downregulation of p22phox and p47phox. Furthermore, puerarin-7-O-glucuronide prevented angiotensin II-induced increases in cell surface area and perimeter, as well as changes in Nppa, Myh7, and Myh6. In the pharmacokinetic study, puerarin-7-O-glucuronide was cleared with a half-life of 0.94 h after intravenous administration. Puerarin could be detected in rat plasma, albeit in low concentration, as early as 5 min after intravenous administration of puerarin-7-O-glucuronide. These anti-oxidant and anti-hypertrophic properties of puerarin-7-O-glucuronide were similar to those of its parent compound puerarin. These results support the development of puerarin-7-O-glucuronide as a novel pharmaceutical agent for therapeutic application.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Solventes / Angiotensina II / Água / Cardiomegalia / Estresse Oxidativo / Glucuronídeos / Miócitos Cardíacos / Isoflavonas / Antioxidantes Idioma: En Revista: Naunyn Schmiedebergs Arch Pharmacol Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Solventes / Angiotensina II / Água / Cardiomegalia / Estresse Oxidativo / Glucuronídeos / Miócitos Cardíacos / Isoflavonas / Antioxidantes Idioma: En Revista: Naunyn Schmiedebergs Arch Pharmacol Ano de publicação: 2017 Tipo de documento: Article