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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.JE

Abstract

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.

Authors+Show Affiliations

Tianjin State Key Laboratory of Modern Chinese Medicine, 312 Anshanxi Road, Nankai District, Tianjin 300193, China.Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 312 Anshanxi Road, Nankai District, Tianjin 300193, China.Tianjin State Key Laboratory of Modern Chinese Medicine, 312 Anshanxi Road, Nankai District, Tianjin 300193, China.Houston Methodist Hospital, 6565 Fannin Street, Houston, TX 77030, USA.Tianjin State Key Laboratory of Modern Chinese Medicine, 312 Anshanxi Road, Nankai District, Tianjin 300193, China.Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 312 Anshanxi Road, Nankai District, Tianjin 300193, China.Tianjin State Key Laboratory of Modern Chinese Medicine, 312 Anshanxi Road, Nankai District, Tianjin 300193, China.Tianjin State Key Laboratory of Modern Chinese Medicine, 312 Anshanxi Road, Nankai District, Tianjin 300193, China. Electronic address: wangt@263.net.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29233733

Citation

Zhang, Yi, et al. "Effect and Mechanism of Dioscin From Dioscorea Spongiosa On Uric Acid Excretion in Animal Model of Hyperuricemia." Journal of Ethnopharmacology, vol. 214, 2018, pp. 29-36.
Zhang Y, Jin L, Liu J, et al. Effect and mechanism of dioscin from Dioscorea spongiosa on uric acid excretion in animal model of hyperuricemia. J Ethnopharmacol. 2018;214:29-36.
Zhang, Y., Jin, L., Liu, J., Wang, W., Yu, H., Li, J., Chen, Q., & Wang, T. (2018). Effect and mechanism of dioscin from Dioscorea spongiosa on uric acid excretion in animal model of hyperuricemia. Journal of Ethnopharmacology, 214, 29-36. https://doi.org/10.1016/j.jep.2017.12.004
Zhang Y, et al. 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. PubMed PMID: 29233733.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect and mechanism of dioscin from Dioscorea spongiosa on uric acid excretion in animal model of hyperuricemia. AU - Zhang,Yi, AU - Jin,Lijun, AU - Liu,Jinchang, AU - Wang,Wei, AU - Yu,Haiyang, AU - Li,Jian, AU - Chen,Qian, AU - Wang,Tao, Y1 - 2017/12/09/ PY - 2017/06/15/received PY - 2017/12/03/revised PY - 2017/12/05/accepted PY - 2017/12/14/pubmed PY - 2018/8/14/medline PY - 2017/12/14/entrez KW - ABCG2 KW - Dioscin KW - Hyperuricemia KW - Tigogenin KW - URAT1 KW - Uric acid excretion SP - 29 EP - 36 JF - Journal of ethnopharmacology JO - J Ethnopharmacol VL - 214 N2 - 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. SN - 1872-7573 UR - https://www.unboundmedicine.com/medline/citation/29233733/Effect_and_mechanism_of_dioscin_from_Dioscorea_spongiosa_on_uric_acid_excretion_in_animal_model_of_hyperuricemia_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-8741(17)32279-1 DB - PRIME DP - Unbound Medicine ER -