Nuciferine restores potassium oxonate-induced hyperuricemia and kidney inflammation in mice.

Abstract

Nuciferine, a major aporphine alkaloid of the leaves of Nelumbo nucifera, was found to decrease serum urate levels and improved kidney function, as well as inhibited system and renal interleukin-1β (IL-1β) secretion in potassium oxonate-induced hyperuricemic mice. Furthermore, nuciferine reversed expression alteration of renal urate transporter 1 (URAT1), glucose transporter 9 (GLUT9), ATP-binding cassette, subfamily G, membrane 2 (ABCG2), organic anion transporter 1 (OAT1), organic cation transporter 1 (OCT1), and organic cation/carnitine transporters 1/2 (OCTN1/2) in hyperuricemic mice. More importantly, nuciferine suppressed renal activation of Toll-like receptor 4/myeloid differentiation factor 88/NF-kappaB (TLR4/MyD88/NF-κB) signaling and NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome to reduce serum and renal IL-1β levels in hyperuricemic mice with renal inflammation reduction. The anti-inflammatroy effect of nuciferine was also confirmed in human proximal renal tubular epithelial cells (HK-2 cells) incubated with 4mg/dl uric acid for 24h. This study firstly reported the anti-hyperuricemic and anti-inflammatory effects of nuciferine by regulating renal organic ion transporters and inflammatory signaling in hyperuricemia. These results suggest that a dietary supplement of nuciferine rich in lotus leaf may be potential for the prevention and treatment of hyperuricemia with kidney inflammation.

• Authors: Ming-Xing Wang, Yang-Liu Liu, Ying Yang, Dong-Mei Zhang, Ling-Dong Kong
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 747 Pg. 59-70 (Jan 15 2015) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 25499818 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Aporphines
• Carrier Proteins
• Inflammasomes
• Interleukin-1beta
• Myeloid Differentiation Factor 88
• NF-kappa B
• NLR Family, Pyrin Domain-Containing 3 Protein
• Nlrp3 protein, mouse
• Organic Anion Transporters
• Tlr4 protein, mouse
• Toll-Like Receptor 4
• urate transporter
• Uric Acid
• potassium oxonate
• Oxonic Acid
• nuciferine

Topics

• Animals
• Aporphines (pharmacology, therapeutic use)
• Carrier Proteins (metabolism)
• Cell Line
• Humans
• Hyperuricemia (chemically induced, drug therapy, metabolism, physiopathology)
• Inflammasomes (metabolism)
• Inflammation (chemically induced, drug therapy, metabolism, physiopathology)
• Interleukin-1beta (metabolism)
• Intestinal Mucosa (metabolism)
• Intestines (drug effects)
• Kidney (drug effects, metabolism, pathology, physiopathology)
• Male
• Mice
• Myeloid Differentiation Factor 88 (metabolism)
• NF-kappa B (metabolism)
• NLR Family, Pyrin Domain-Containing 3 Protein
• Organic Anion Transporters (metabolism)
• Oxonic Acid (adverse effects)
• Signal Transduction (drug effects)
• Toll-Like Receptor 4 (metabolism)
• Uric Acid (blood, metabolism)