Comparative pharmacokinetic study on phenolic acids and flavonoids in spinal cord injury rats plasma by UPLC-MS/MS after single and combined oral administration of danshen and huangqin extract

J Pharm Biomed Anal. 2019 Aug 5:172:103-112. doi: 10.1016/j.jpba.2019.04.024. Epub 2019 Apr 20.

Abstract

Chinese medicinal herbs danshen and huangqin have attracted attention in spinal cord injury (SCI) treatment. Purpose of this study was to investigate and compare the pharmacokinetic characteristics of 4 phenolic acids and 4 flavonoids in SCI rat plasma after orally administrate danshen, huangqin and combined extract of these two herbs (CDH). Thus, a rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for simultaneously quantitative determination of tanshinol, protocatechualdehyde, protocatechuic acid, salvianolic acid A, baicalein, baicalin, wogonin and wogonoside. After inducing a contusion injury by a weight-drop device, SCI rats were orally administrated a single dose (12.5 g/kg) of danshen, huangqin and CDH extracts, respectively. Then, blood samples at different time points were collected and analyzed. In CDH group, Cmax and AUC of tanshinol, protocatechualdehyde and protocatechuic acid significantly declined, while those of salvianolic acid A enhanced. These changes were beneficial for danshen to treat SCI. As for flavonoids, double peaks were observed in huangqin group, while this phenomenon disappeared in CDH group. Concomitantly, Cmax and AUC declined after administrated CDH. These alterations were due to influence of danshen active constituents on absorption and transportation process of flavonoids. Therefore, danshen and huangqin significantly influenced pharmacokinetic profile and parameters of each other, thus exert synergistic therapeutic effect in SCI treatment.

Keywords: Flavonoids; Pharmacokinetics; Phenolic acids; Spinal cord injury; UPLC-MS/MS.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Animals
  • Area Under Curve
  • Chromatography, High Pressure Liquid
  • Disease Models, Animal
  • Drug Combinations
  • Drug Synergism
  • Drugs, Chinese Herbal / administration & dosage
  • Drugs, Chinese Herbal / pharmacokinetics*
  • Flavonoids / blood
  • Humans
  • Hydroxybenzoates / blood
  • Rats
  • Rats, Sprague-Dawley
  • Salvia miltiorrhiza / chemistry*
  • Scutellaria baicalensis / chemistry*
  • Spinal Cord Injuries / blood
  • Spinal Cord Injuries / drug therapy*
  • Spinal Cord Injuries / etiology
  • Tandem Mass Spectrometry

Substances

  • Drug Combinations
  • Drugs, Chinese Herbal
  • Flavonoids
  • Hydroxybenzoates
  • dan-shen root extract
  • phenolic acid