Astilbin improves potassium oxonate-induced hyperuricemia and kidney injury through regulating oxidative stress and inflammation response in mice.

Abstract

Astilbin is a flavonoid compound derived from the rhizome of Smilax china L. The effects and possible molecular mechanisms of astilbin on potassium oxonate-induced hyperuricemia mice were investigated in this study. Different dosages of astilbin (5, 10, and 20mg/kg) were administered to induce hyperuricemic mice. The results demonstrated that the serum uric acid (Sur) level was significantly decreased by increasing the urinary uric acid (Uur) level and fractional excretion of urate (FEUA) with astilbin, related with suppressing role in meditation of Glucose transporter 9 (GLUT9), Human urate transporter 1 (URAT1) expression and up-regulation of ABCG2, Organic anion transporter 1/3 (OAT1/3) and Organic cation transporter 1 (OCT1). In addition, kidney function parameters, including serum creatinine (Scr) and blood urea nitrogen (BUN) were restored in astilbin-treated hyperuricemic rats. Further investigation indicated that astilbin prevented the renal damage against the expression of Thioredoxin-interacting protein (TXNIP) and its related inflammation signal pathway, including NLR pyrin domain-containing 3/Nuclear factor κB (NLRP3/NF-κB), which is associated with the up-regulation of interleukin-1β (IL-1β) and interleukin-18 (IL-18), and also presented a renal protective role by suppression oxidative stress. Moreover, astilbin inhibited activation of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) cascade and over-expression of suppressor of cytokine signaling 3 (SOCS3) in the kidneys of potassium oxonate-induced mice. These findings provide potent evidence and therapeutic strategy for astilbin as a safe and promising compound in the development of a disease-modifying drug due to its function against hyperuricaemia and renal injury induced by potassium oxonate.

• Authors: Ming Wang, Jing Zhao, Nan Zhang, Jianghua Chen
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 83 Pg. 975-988 (Oct 2016) ISSN: 1950-6007 [Electronic] France
• PMID: 27522260 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Chemical References

• Carrier Proteins
• Flavonols
• Inflammasomes
• Membrane Transport Proteins
• NF-kappa B
• NLR Family, Pyrin Domain-Containing 3 Protein
• Nlrp3 protein, mouse
• STAT3 Transcription Factor
• Txnip protein, mouse
• Uric Acid
• astilbin
• potassium oxonate
• Thioredoxins
• Oxonic Acid
• Janus Kinase 2

Topics

• Animals
• Carrier Proteins (metabolism)
• Flavonols (chemistry, pharmacology, therapeutic use)
• Hyperuricemia (blood, chemically induced, drug therapy, pathology)
• Inflammasomes (metabolism)
• Inflammation (blood, pathology)
• Janus Kinase 2 (metabolism)
• Kidney (drug effects, pathology, physiopathology)
• Male
• Membrane Transport Proteins (metabolism)
• Mice
• NF-kappa B (metabolism)
• NLR Family, Pyrin Domain-Containing 3 Protein (metabolism)
• Oxidative Stress (drug effects)
• Oxonic Acid
• Podocytes (drug effects, metabolism, pathology)
• STAT3 Transcription Factor (metabolism)
• Signal Transduction (drug effects)
• Thioredoxins (metabolism)
• Uric Acid (blood)