Nuciferine Protects against Obesity-Induced Nephrotoxicity through Its Hypolipidemic, Anti-Inflammatory, and Antioxidant Effects

High-fat diets (HFD) could cause obesity, trigger lipid accumulation, and induce oxidative stress and inflammation, leading to kidney damage. This study aimed to elucidate the protective effects of nuciferine on HFD-caused nephrotoxicity and explore the underlying mechanisms in Kunming mice and palmitic acid-exposed HK-2 cells. In obese mice, nuciferine notably alleviated HFD-induced chronic renal dysfunction and delayed renal fibrosis progression and podocyte apoptosis, as evidenced by the increased expressions of renal function factors BUN, CRE, and UA and the decreased expressions of key protein factors TGF-β1, p-Samd3, Wnt-1, and β-catenin. Nuciferine also effectively attenuated HFD-induced renal lipid accumulation via the AMPK-mediated regulation of FAS and HSL expressions and suppressed inflammation and oxidative stress via the AMPK-mediated Nrf-2/HO-1 and TLR4/MyD88/NF-κB pathways. In addition, consistent with the results of animal experiments, nuciferine remarkably reversed cell damage and attenuated lipid accumulation, inflammation, and oxidative stress in palmitic acid-exposed HK-2 cells through the AMPK-mediated signaling pathway. Therefore, nuciferine could be a new food-derived protective agent to offset obesity and correlative kidney damage.