Distribution kinetics of puerarin in rat hippocampus after acute local cerebral ischemia

J Pharm Biomed Anal. 2019 Feb 5:164:196-201. doi: 10.1016/j.jpba.2018.10.038. Epub 2018 Oct 25.

Abstract

Puerarin, isolated from the roots of Pueraria lobata, is widely used for treating cerebral ischemia in China. The time- and dose-dependent distribution characteristics of puerarin in the ischemic hippocampus are unknown. In this study, puerarin concentration was determined by an indirect competitive ELISA using anti-puerarin monoclonal antibody. Area under the curve (AUC0-120 min) of puerarin (80 mg/kg) in the embolic hippocampus was higher than that in the normal hippocampus; the increase was significant only at 40 and 20 mg/kg. The maximum concentration (Cmax) of puerarin in the embolic hippocampus was higher than that in the normal hippocampus at all doses. The increase in both AUC0-120 min and Cmax was dose-dependent. Time to reach the maximum concentration (Tmax) of puerarin in the embolic and normal hippocampus was similar. Although the mean residence time in the embolic hippocampus differed from that in the normal hippocampus at 40 and 80 mg/kg, it was higher in the embolic hippocampus than in the normal hippocampus at 20 mg/kg. This is the first study to report that the time- and dose-dependent distribution characteristics of puerarin in the normal and embolic hippocampus after middle cerebral artery occlusion in rats dictate puerarin dose and duration to treat stroke.

Keywords: Acute local cerebral ischemia; Hippocampus; Indirect competitive enzyme-linked immunosorbent assay; Pharmacokinetics; Puerarin; Tissue distribution.

MeSH terms

  • Acute Disease / therapy
  • Animals
  • Area Under Curve
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / etiology
  • Brain Ischemia / pathology
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay / methods
  • Hippocampus / blood supply
  • Hippocampus / chemistry*
  • Hippocampus / pathology
  • Infarction, Middle Cerebral Artery / complications
  • Injections, Intraperitoneal
  • Isoflavones / administration & dosage
  • Isoflavones / pharmacokinetics*
  • Plant Roots / chemistry
  • Pueraria / chemistry*
  • Rats
  • Time Factors
  • Tissue Distribution
  • Vasodilator Agents / administration & dosage
  • Vasodilator Agents / pharmacokinetics*

Substances

  • Isoflavones
  • Vasodilator Agents
  • puerarin