DIGESTED WHEY PEPTIDE INDUCES ANTIOXIDANT AND ANTI-INFLAMMATORY BIOACTIVITY ON GLIAL CELLS.

Brain functionality is prone to inflammatory and oxidative aggravations. Increasing interest has been directed to the potential neuroprotective activities of food derived peptide, specifically whey. Few studies evaluated the bioactivity of whey peptides on glia brain cells. Astrocytes and microglia play a key role in normal brain function and immunity. Any dysfunction of this cells is associated with neurodegeneration. In this work we evaluated the neuroprotective potentiality of peptides formed during in vitro digestion on glial lineage cells. Whey protein isolates were hydrolyzed (WPH) by simulated gastric digestion (Infogest protocol) and fractionated with <5 kDa ultrafiltration. Whey digestion induced high degree of hydrolysis (35.2 ± 2,4 %), and small molecular range peptide (68 % less than 400 Da) analyzed by FPLC. Although high content of hydrophobic amino acids, peptide showed low to medium surface hydrophobicity by HPLC. WPH showed no toxicity on astrocytes (C6 cell line) and microglia (BV2 cell line) at different concentrations (0.5 to 2 mg/mL), measured by MTT assay. WPH attenuated H2O2 induced oxidative stress in astroglia and microglia cells in a dose dependent manner, measured by DCF assay. LPS inflammatory stimulus induced a reduction on GSH content in astroglia cells and an increase in oxide nitric (NO) secretion on microglia cell line. WPH was able to attenuate each of the effect, so increasing GSH content and reducing NO secretion, observed by colorimetric methods. SOD activity was not affected by LPS or WPH treatment. WPH protected glial cells against LPS inflammatory stimulus, reducing mRNA expression of IL-1β, IL-6 and TNF. Our results show that whey peptides, resistant to the digestion process, may be more likely to have functional effects on brain cells and big potential to produce new neuroprotective compounds.