title: Nuciferine Alleviates Renal Injury by Inhibiting Inflammatory Responses in Fructose-Fed Rats.
abstract: Nuciferine is a major active component from the lotus leaf. This study examines the effects of nuciferine on fructose-induced renal injury and explores its possible mechanism. Rats consumed drinking water or 10% fructose for 12 weeks. Fructose-fed rats were orally treated with water or 7, 14, or 28 mg/kg of nuciferine for the last 6 weeks. HK-2 cells were exposed to 5 mM fructose alone or in combination with nuciferine (2.5-40 μM) for 24 h. Nuciferine significantly attenuated fructose-induced hyperuricemia, dyslipidemia, and systemic inflammation in rats. More importantly, it alleviated renal pathological injury with proteinuria at 20 and 40 mg/kg (2.58 ± 0.97 and 2.48 ± 1.04 mg/mg·creatinine, P < 0.05) compared with fructose-vehicle group (4.10 ± 1.18 mg/mg·creatinine). Furthermore, nuciferine reduced TLR4, MyD88, PI3K, ILK, p-AKT, p-P65, and NLRP3 inflammasome protein levels (P < 0.05 for all) in the renal cortex of fructose-fed rats (14 and 28 mg/kg) and fructose-exposed HK-2 cells (5-40 μM), which is consistent with its reduction of inflammatory cytokines IL-1β, IL-6, TNF-α, and MCP-1 (P < 0.05 for all) in vivo and in vitro. These findings suggest that nuciferine alleviated fructose-induced inflammation by inhibiting TLR4/PI3K/NF-κB signaling and NLRP3 inflammasome activation in rat renal cortex and HK-2 cells, which may contribute to the improvement of renal injury.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University , Nanjing 210023, 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 Sciences, Nanjing University , Nanjing 210023, People's Republic of China.
authors.forename: Xiao-Juan
authors.initials: XJ
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University , Nanjing 210023, People's Republic of China.
authors.forename: Tian-Yu
authors.initials: TY
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University , Nanjing 210023, 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 Sciences, Nanjing University , Nanjing 210023, People's Republic of China.
authors.forename: Rui-Qing
authors.initials: RQ
authors.lastname: Jiao
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University , Nanjing 210023, People's Republic of China.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University , Nanjing 210023, People's Republic of China.
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University , Nanjing 210023, People's Republic of China.
authors.forename: Jia-Hui
authors.initials: JH
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University , Nanjing 210023, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Pan
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University , Nanjing 210023, People's Republic of China.
authors.forename: Ling-Dong
authors.initials: LD
authors.lastname: Kong
keywords: fructose-exposed HK-2 cells; fructose-fed rats; nuciferine; renal inflammation; renal injury