Research on the pharmacodynamics and mechanism of Fraxini Cortex on hyperuricemia based on the regulation of URAT1 and GLUT9

Biomed Pharmacother. 2018 Oct:106:434-442. doi: 10.1016/j.biopha.2018.06.163. Epub 2018 Jul 11.

Abstract

Fraxini Cortex (also known as Qinpi, QP) has been used for the treatment of hyperuricemia with a significant difference on efficacy of QP from different regions. However, it`s still unknown whether proportion of components is the key and why same kind of herbs have different therapeutic effects. In this study, different sources of QP were collected from Shaanxi Qinpi extracts (SQPE), Henan Qinpi extracts (HQPE), Hebei Qinpi extracts (GQPE) provinces in China. Rat model of hyperuricemia with hypoxanthine combined with potassium oxonate were established to determine the levels of blood urea nitrogen (BUN), serum uric acid (SUA), urine uric acid (UUA) and creatinine (Cr). Hematoxylin-eosin staining (H&E) and Periodic Acid-Schiff staining (PAS) were performed for renal pathology while Western blot analysis and real-time PCR analysis for proteins and mRNA expression levels. High-performance liquid chromatograph (HPLC) was used for components and composition analysis. Our results demonstrated that QPE from different regions could alleviate hyperuricemia via increasing significantly the SCr and BUN levels whereas decreasing markedly UCr, SUA and UUA levels. Additionally, QPE could also improve the pathological changes of the kidneys. The protein and mRNA levels of urate reabsorption transporter 1 (URAT1) and glucose transporter 9 (GLUT9) were down-regulated by QPE treatment. SQPE hold a better activity on improving hyperuricemia and regulating URAT1 and GLUT9. HPLC analysis showed that the proportion of four components aesculin, aesculetin, fraxin, fraxetin were 9.002: 0.350: 8.980: 0.154 (SQPE); 0.526: 0.164: 7.938: 0.102 (HQPE); 12.022: 1.65: 0.878: 1.064 (GQPE). These data indicate that this proportion of effective components may be an important factor for efficacy of QP and had implications for the treatment of hyperuricemia.

Keywords: Fraxini Cortex; GLUT9; Hyperuricemia; Structural proportion of components; URAT1.

Publication types

  • Comparative Study

MeSH terms

  • Aesculus
  • Animals
  • Anion Transport Proteins / genetics
  • Anion Transport Proteins / metabolism*
  • Biomarkers / blood
  • Biomarkers / urine
  • Blood Urea Nitrogen
  • Coumarins / analysis
  • Coumarins / pharmacology
  • Creatinine / urine
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Drugs, Chinese Herbal / analysis
  • Drugs, Chinese Herbal / pharmacology*
  • Esculin / analysis
  • Esculin / pharmacology
  • Gout Suppressants / analysis
  • Gout Suppressants / pharmacology*
  • Hyperuricemia / drug therapy*
  • Hyperuricemia / genetics
  • Hyperuricemia / metabolism
  • Hyperuricemia / physiopathology
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / physiopathology
  • Male
  • Monosaccharide Transport Proteins / genetics
  • Monosaccharide Transport Proteins / metabolism*
  • Rats, Sprague-Dawley
  • Recovery of Function
  • Umbelliferones / analysis
  • Umbelliferones / pharmacology
  • Uric Acid / blood
  • Uric Acid / metabolism*
  • Uric Acid / urine

Substances

  • Anion Transport Proteins
  • Biomarkers
  • Coumarins
  • Drugs, Chinese Herbal
  • GLUT6 protein, rat
  • Gout Suppressants
  • Monosaccharide Transport Proteins
  • Slc22a12 protein, rat
  • Umbelliferones
  • Esculin
  • Uric Acid
  • horse chestnut seed
  • Creatinine
  • fraxetin
  • esculetin
  • fraxin