A Natural Dietary Supplement with a Combination of Nutrients Prevents Neurodegeneration Induced by a High Fat Diet in Mice

Obesity and metabolic disorders can be risk factors for the onset and development ofneurodegenerative diseases. The aim of the present study was to investigate the protective effects ofa natural dietary supplement (NDS), containing Curcuma longa, silymarin, guggul, chlorogenic acidand inulin, on dysmetabolism and neurodegeneration in the brains of high fat diet (HFD)-fed mice.Decrease in the expression of FACL-4, CerS-1, CerS-4, cholesterol concentration and increase in theinsulin receptor expression and insulin signaling activation, were found in brains of NDS-treatedHFD brains in comparison with HFD untreated-mice, suggesting that NDS is able to prevent brainlipid accumulation and central insulin resistance. In the brains of NDS-treated HFD mice, the levelsof RNS, ROS and lipid peroxidation, the expression of p-ERK, H-Oxy, i-NOS, HSP60, NF-kB, GFAP,IL-1, IL-6 and CD4 positive cell infiltration were lower than in untreated HFD mice, suggestingantioxidant and anti-inflammatory effects of NDS. The decreased expression of p-ERK and GFAP inNDS-treated HFD mice was confirmed by immunofluorescence. Lastly, a lower number of apoptoticnuclei was found in cortical sections of NDS-treated HFD mice. The present data indicate that NDSexerts neuroprotective effects in HFD mice by reducing brain fat accumulation, oxidative stress andinflammation and improving brain insulin resistance.