Nuciferine Alleviates Renal Injury by Inhibiting Inflammatory Responses in Fructose-Fed Rats

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.