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Pharmacokinetic and metabolomic analyses of the neuroprotective effects of salvianolic acid A in a rat ischemic stroke model.
Feng, Si-Qi; Aa, Nan; Geng, Jian-Liang; Huang, Jing-Qiu; Sun, Run-Bin; Ge, Chun; Yang, Zhi-Jian; Wang, Lian-Sheng; Aa, Ji-Ye; Wang, Guang-Ji.
Afiliação
  • Feng SQ; Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China.
  • Aa N; Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
  • Geng JL; Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China.
  • Huang JQ; Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China.
  • Sun RB; Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China.
  • Ge C; Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China.
  • Yang ZJ; Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
  • Wang LS; Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
  • Aa JY; Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China.
  • Wang GJ; Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China.
Acta Pharmacol Sin ; 38(11): 1435-1444, 2017 Nov.
Article em En | MEDLINE | ID: mdl-28836583
ABSTRACT
Salvianolic acid A (SAA), a water-soluble phenolic acid isolated from the root of Dan Shen, displays distinct antioxidant activity and effectiveness in protection against cerebral ischemia/reperfusion (I/R) damage. However, whether SAA can enter the central nervous system and exert its protective effects by directly targeting brain tissue remains unclear. In this study, we evaluated the cerebral protection of SAA in rats subjected to transient middle cerebral artery occlusion (tMCAO) followed by reperfusion. The rats were treated with SAA (5, 10 mg/kg, iv) when the reperfusion was performed. SAA administration significantly decreased cerebral infarct area and the brain water content, attenuated the neurological deficit and pathology, and enhanced the anti-inflammatory and antioxidant capacity in tMCAO rats. The concentration of SAA in the plasma and brain was detected using LC-MS/MS. A pharmacokinetic study revealed that the circulatory system exposure to SAA was equivalent in the sham controls and I/R rats, but the brain exposure to SAA was significantly higher in the I/R rats than in the sham controls (fold change of 9.17), suggesting that the enhanced exposure to SAA contributed to its cerebral protective effect. Using a GC/MS-based metabolomic platform, metabolites in the serum and brain tissue were extracted and profiled. According to the metabolomic pattern of the tissue data, SAA administration significantly modulated the I/R-caused perturbation of metabolism in the brain to a greater extent than that in the serum, demonstrating that SAA worked at the brain tissue level rather than the whole circulation system. In conclusion, a larger amount of SAA enters the central nervous system in ischemia/reperfusion rats to facilitate its protective and regulatory effects on the perturbed metabolism.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Encéfalo / Ácidos Cafeicos / Traumatismo por Reperfusão / Fármacos Neuroprotetores / Infarto da Artéria Cerebral Média / Metabolômica / Lactatos Limite: Animals Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Encéfalo / Ácidos Cafeicos / Traumatismo por Reperfusão / Fármacos Neuroprotetores / Infarto da Artéria Cerebral Média / Metabolômica / Lactatos Limite: Animals Idioma: En Ano de publicação: 2017 Tipo de documento: Article