title: 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.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, People׳s Republic of China.
authors.forename: Ming-Xing
authors.initials: MX
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, People׳s Republic of China.
authors.forename: Yang-Liu
authors.initials: YL
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, People׳s Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, People׳s Republic of China.
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, People׳s Republic of China. Electronic address: kongld@nju.edu.cn.
authors.forename: Ling-Dong
authors.initials: LD
authors.lastname: Kong
mesh_terms: D000818:Animals; D001060:Aporphines / Q000494:pharmacology* / Q000627:therapeutic use; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D033461:Hyperuricemia / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D058847:Inflammasomes / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D053583:Interleukin-1beta / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D027361:Organic Anion Transporters / Q000378:metabolism; D010094:Oxonic Acid / Q000009:adverse effects*; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014527:Uric Acid / Q000097:blood / Q000378:metabolism
chemical_list: D001060:Aporphines; D002352:Carrier Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D027361:Organic Anion Transporters; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; C103862:urate transporter; D014527:Uric Acid; C489337:potassium oxonate; D010094:Oxonic Acid; C008692:nuciferine
keywords: Hyperuricemia; NF-κB; NLRP3 inflammasome; Nuciferine; Organic ion transporters; TLR signaling