Fig. 12

Malva parviflora hydroalcoholic extract regulates PPARγ levels in the 5XFAD transgenic mice. The 5XFAD and Wt mice were fed with either normal diet (ND) or high-fat diet (HFD) non-treated (Vehicle) or treated with M. parviflora hydroalcoholic extract (M. parviflora). The PPAR-γ levels from the frontal cortex cell extracts were determined by immunoblot using specific antibodies and the GAPDH levels were used as internal control. a Normalized densitometry values of PPAR-γ (PPAR-γ/GAPDH) present in the frontal cortex cell extracts of 5XFAD and Wt mice. Data (mean ± SD) were analyzed by three-way ANOVA followed by Tukey’s multiple comparisons test. This analysis revealed a significant effect for the genotype F(1,16) = 7.529, p = 0.0144; for the diet F(1,16) = 13.37, p = 0-0021; for the M. parviflora treatment F(1,16) = 28.11, p < 0.0001; for the genotype and diet interaction F(1,16) = 0.5415, p = 0.4725; for the M. parviflora treatment and diet interaction F(1,16) = 17.37, p = 0.0007; for the genotype and M. parviflora treatment interaction F(1,16) = 6.946, p < 0.0180; for the genotype, M. parviflora treatment and diet interaction F(1,16) = 6.111, p = 0.0250. b Microglial primary cultures were left untreated or pre-treated with GW9662, a specific PPAR-γ inhibitor for 1 h, following by incubation with oleanolic acid (OA), at the indicated concentration for 24 h. The PPAR-γ levels from the cell extracts of microglial primary cultures were determined by immunoblot using specific antibodies and the GAPDH levels were used as internal control. Normalized densitometry values of PPAR- γ (PPAR- γ/GAPDH) present in the extracts of microglial primary cultures in the presence of oleanolic acid. Data (mean ± SD) were analyzed by one-way ANOVA followed by Tukey’s post hoc test. Ctrl vs 4.5 μg/mL oleanolic acid (*p = 0.0414); 4.5 μg/mL oleanolic acid vs GW9662 + oleanolic acid 4.5 μg/mL (*p = 0.0116); 45 μg/mL oleanolic acid vs GW9662 + 45 μg/mL oleanolic acid (**p = 0.0079); c Model of the mechanism by which M. parviflora hydroalcoholic extract (HE) diminishes neuroinflammation. Chronic inflammation compromises microglia clearance functions by reducing the expression of the scavenger receptor CD36. The peroxisome proliferator-activated receptor (PPAR-γ) suppress inflammatory gene expression and promotes phagocytosis by regulating CD36 expression a scavenger receptor involved in microglia-dependent amyloid plaque destruction. According with this, our results indicate that a component present in the M. parviflora extract, probably oleanolic acid, based on previous studies [43] and our data, induces PPAR-γ activation that results in the upregulation of the scavenger receptor CD36 expression, thus leading to microglia-enhanced phagocytic, amyloid plaque clearance activity, diminished neuroinflammation, and improved learning and memory