Microglia respond to adverse stimuli in order to restore brain homeostasis and, upon activation, they release a number of inflammatory mediators. Chronic microglial overactivation is related to neuroinflammation in Alzheimer’s disease. In this work, we show that oleanolic acid (OA), a natural triterpene present in food and medicinal plants, attenuates the activation of BV2 microglial cells induced by lipopolysaccharide (LPS). Cell pretreatment with OA inhibited the release of IL-1β, IL-6, TNF-α, and NO, which was associated with the downregulation of the expression of genes encoding for these cytokines and inducible nitric oxide synthase (iNOS), and the reinforcement of the endogenous antioxidant cell defense. These findings advocate considering OA as a novel neuroprotective agent to inhibit oxidative stress and inflammatory response in activated microglia associated with Alzheimer’s disease.

26The effect of GPETAFLR, a peptide isolated from Lupinus angustifolius L. 27 protein hydrolysate (LPH), on osteoclastogenesis was investigated. Human 28 osteoclasts generated from monocytes were used to analyse the effects of 29 GPETAFLR (50-100 µg/mL) on osteoclastogenesis using TRAP reaction, RT-30 qPCR, and ELISA procedures. LPS enhanced TRAP activity and the expression 31 of osteoclast marker genes (TRAP, OSCAR, RANK, and CATHK) while 32 downregulated the expression of OPG gene in human monocyte-derived 33 osteoclasts. These effects were reduced with GPETAFLR. Moreover, LPS 34 increased the release of osteoclastogenic cytokines (TNF-, IL-1, and IL-6) 35 meanwhile GPETAFLR increased the release of anti-osteoclastogenic cytokines 36 (IL-4 and IL-10) in the medium of human monocyte-derived osteoclasts. For the 37 first time, we show that plant peptides from lupine protein hydrolysates have 38 anti-osteoclastogenic activity. These exciting findings open opportunities for 39 developing nutritional strategies with Lupinus angustifolius L. as dietary source 40 of plant proteins, notably GPETAFLR, to prevent development and progression 41 of osteoclast-related diseases. 42 43 44 45 46 47 65 cells that adhere to the bone matrix and secrete acids and lithic enzymes 66 resulting in bone degradation (Kalbasi Anaraki et al., 2015). The differentiation 67 of monocytes into OCs, a multi-complex procedure referred to as 68 osteoclastogenesis, is induced by two crucial cytokines: macrophage colony-69 stimulating factor (M-CSF) and RANKL. In addition to M-CSF and RANKL as 70 the only factors required for basal osteoclastogenesis, several other cytokines 71 such as TNF-, IL-1, and IL-6 also play an important role in OC biology. These 72 osteoclastogenic cytokines promote bone resorption through multiple 73 mechanisms that include the increase of M-CSF and RANKL production 74 (Zupan, Jeras, & Marc, 2013). 307 T.M., … Oliveira, R.C. (2014). Effects of fluoride in bone repair: an evaluation of 308 RANKL, OPG and TRAP expression. Odontology, 102, 22-30.

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Chia (Salvia hispanica L.) seed has high potential in the development of functional food due to its protein content with a special amino acid profile. Among the hematopoietic-derived cells, monocytes are endowed with high plasticity, responsible for their pro- and anti-inflammatory function in M1 and M2 phenotype polarization, respectively. Indeed, monocytes are involved in several oxidative- and inflammatory-associated disorders such as cancer, obesity, and cardiovascular and neurodegenerative diseases. This study was designed to investigate the role of chia protein hydrolysates (CPHs) in primary human monocyte–macrophage plasticity response using biochemical, RT-qPCR, and ELISA assays. Our results showed that CPHs reduce ROS and nitrite output, as pro-inflammatory cytokine secretion, and enhance the expression and release of anti-inflammatory cytokines. In addition, CPHs reverse LPS-associated M1 polarization into M2. These findings open new opportunities for developing nutritional strategies with chia as a dietary source of biopeptides to prevent the development and progression of oxidative- and inflammatory-related diseases.