Effect and mechanism of dioscin from Dioscorea spongiosa on uric acid excretion in animal model of hyperuricemia

J Ethnopharmacol. 2018 Mar 25:214:29-36. doi: 10.1016/j.jep.2017.12.004. Epub 2017 Dec 9.


Ethnopharmacology relevance: Dioscin, a spirostane glycoside, the rhizoma of Dioscorea septemloba (Diocoreacea) is used for diuresis, rheumatism, and joints pain. Given the poor solubility and stability of Dioscin, we proposed a hypothesis that Dioscin's metabolite(s) are the active substance(s) in vivo to contribute to the reducing effects on serum uric acid levels.

Aim of the study: The aim of this study is to identify the active metabolite(s) of Dioscin in vivo and to explore the mechanism of its antihyperuricemic activity.

Materials and methods: After oral administration of Dioscin in potassium oxonate (PO) induced hyperuricemia rats and adenine-PO induced hyperuricemia mice models, serum uric acid and creatinine levels, clearance of uric acid and creatinine, fractional excretion of uric acid, and renal pathological lesions were determined were used to evaluate the antihyperuricemic effects. Renal glucose transporter-9 (GLUT-9) and organic anion transporter-1 (OAT-1) expressions were analyzed by western blotting method. Renal uric acid excretion was evaluated using stably urate transporter-1 (URAT-1) transfected human epithelial kidney cell line. Intestinal uric acid excretion was evaluated by measuring the transcellular transport of uric acid in HCT116 cells.

Results: In hyperuricemia rats, both 25 and 50mg/kg of oral Dioscin decreased serum uric acid levels over 4h. In the hyperuricemia mice, two weeks treatment of Dioscin significantly decreased serum uric acid and creatinine levels, increased clearance of uric acid and creatinine, increased fractional excretion of uric acid, and reduced renal pathological lesions caused by hyperuricemia. In addition, renal GLUT -9 was significantly down-regulated and OAT-1 was up-regulated in Dioscin treated hyperuricemia mice. Dioscin's metabolite Tigogenin significantly inhibited uric acid re-absorption via URAT1 from 10 to 100μM. Diosgenin and Tigogenin increased uric acid excretion via ATP binding cassette subfamily G member 2 (ABCG2).

Conclusion: Decreasing effect of Dioscin on serum uric acid level and enhancing effect on urate excretion were confirmed in hyperuricemia animal models. Tigogenin, a metabolite of Dioscin, was identified as an active substance with antihyperuricemic activity in vivo, through inhibition of URAT1 and promotion of ABCG2.

Keywords: ABCG2; Dioscin; Hyperuricemia; Tigogenin; URAT1; Uric acid excretion.

MeSH terms

  • Adenine
  • Animals
  • Biomarkers / blood
  • Creatinine / blood
  • Dioscorea* / chemistry
  • Diosgenin / analogs & derivatives*
  • Diosgenin / isolation & purification
  • Diosgenin / pharmacology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Glucose Transport Proteins, Facilitative / metabolism
  • HCT116 Cells
  • Humans
  • Hyperuricemia / blood
  • Hyperuricemia / chemically induced
  • Hyperuricemia / drug therapy*
  • Intestinal Elimination / drug effects
  • Intestinal Mucosa / metabolism
  • Intestines / drug effects
  • Male
  • Mice
  • Organic Anion Transport Protein 1 / metabolism
  • Organic Anion Transporters / genetics
  • Organic Anion Transporters / metabolism
  • Organic Cation Transport Proteins / genetics
  • Organic Cation Transport Proteins / metabolism
  • Oxonic Acid
  • Phytotherapy
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plants, Medicinal
  • Rats, Sprague-Dawley
  • Renal Elimination / drug effects*
  • Spirostans / isolation & purification
  • Spirostans / pharmacology*
  • Time Factors
  • Uric Acid / blood*
  • Uricosuric Agents / isolation & purification
  • Uricosuric Agents / pharmacology*


  • Biomarkers
  • Glucose Transport Proteins, Facilitative
  • Organic Anion Transport Protein 1
  • Organic Anion Transporters
  • Organic Cation Transport Proteins
  • Plant Extracts
  • SLC22A12 protein, human
  • Slc22a12 protein, mouse
  • Slc22a6 protein, mouse
  • Slc2a9 protein, mouse
  • Spirostans
  • Uricosuric Agents
  • Uric Acid
  • dioscin
  • potassium oxonate
  • Oxonic Acid
  • Creatinine
  • sarsasapogenin
  • Adenine
  • Diosgenin