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Study of the anti-inflammatory action of peptides derived from whey on glial cells


Neuroinflammation is a common process in several chronic degenerative diseases, such as Alzheimer's Disease (AD) and Parkinson's. Bioactive peptides derived from dietary proteins have been studied as important natural anti-inflammatory agents as a safer alternative to side effects induced by synthetic anti-inflammatories. Glial cells, particularly astrocytes and microglia, are the major immune cells of the central nervous system and play an important role in neuroinflammation. Despite, few studies evaluate the potential effects of bioactive peptides on neuroinflammation in these cells. This project aims to implement a cell culture laboratory in the Institute of Food Technology (ITAL) with the intention of developing research that use cell culture as a biological model. As specific objective, this study aims to obtain, characterize and valuate the mechanisms of internalization of bioactive peptides derived from whey with anti-inflammatory capacity in glial cells. Whey peptides will be obtained from pepsin and pancreatin hydrolysis following the Infogest protocol. Peptide fractions will be obtained from ultrafiltration and those smaller than 5 kDa will be isolated by RP-HPLC. Peptide isolates (PI) will be evaluated for their structure by mass spectroscopy, bioavailability in Caco-2 cells, and for their bioactivity in astrocyte lineage and microglia. PIs will be tested for anti-inflammatory activity in cells stimulated with LPS. GFAP, Iba-1, TLR-4 and Cox-2 expression will be tested by immunoblotting, TNF± secretion, IL-1² by ELISA and NFkB pathway activation by immunocytochemistry. The IP with higher bioactivity will be analyzed in silico on the interaction with inflammatory markers. The most interacting will be synthesized, and, with international collaboration, it will be studying the mechanisms of internalization of the peptide chosen by confocal microscopy. It is expected with this project to form a new line of research in ITAL, allowing studies of greater scientific impact and aiming the formation of human resources with multidisciplinary projects. In addition, this study contributes to the formation of new food therapeutic peptides with anti-inflammatory properties in chronic degenerative diseases. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DE ESPINDOLA, JULIANA SANTOS; TACCOLA, MILENA FERREIRA; DA SILVA, VERA SONIA NUNES; DOS SANTOS, LUCILENE DELAZARI; ROSSINI, BRUNO CESAR; MENDONCA, BRUNA CAVECCI; PACHECO, MARIA TERESA BERTOLDO; GALLAND, FABIANA. Digestion-resistant whey peptides promote antioxidant effect on Caco-2 cells. Food Research International, v. 173, p. 12-pg., . (19/01896-4)
PINILLA, CRISTIAN MAURICIO BARRETO; BRANDELLI, ADRIANO; GALLAND, FABIANA; SPADOTI, LEILA MARIA; ALVES, ADRIANA TORRES SILVA E. Improved functional properties of the potential probiotic Lacticaseibacillus paracasei ItalPN16 growing in cheese whey. Letters in Applied Microbiology, v. 76, n. 7, p. 9-pg., . (21/04987-0, 19/01896-4)

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