GPETAFLR, a peptide from Lupinus angustifolius L. prevents inflammation in microglial cells and confers neuroprotection in brain

ABSTRACT

Objectives: Neuroinflammation is a complex inflammatory process in the central nervous system (CNS) where microglia may play a critical role. GPETAFLR is a peptide isolated from Lupinus angustifolius L. protein hydrolysates with functional activity in mononuclear phagocytes. However, it is unknown whether GPETAFLR has neuroprotective effects.

Methods: We analysed the potential anti-neuroinflammatory activity of GPETAFLR by using two different models of neuroinflammation: BV-2 microglial cells and mice with high-fat diet (HFD)-induced obesity.

Results: GPETAFLR hampered LPS-induced upregulation of pro-inflammatory and M1 marker genes in BV-2 cells. This effect was accompanied by an unchanged expression of anti-inflammatory IL-10 gene and by an increased expression of M2 marker genes. GPETAFLR also increased the transcriptional activity of M2 marker genes, while the microglia population remained unchanged in number and M1/M2 status in brain of mice with high-fat diet (HFD)-induced obesity. Furthermore, GPETAFLR counteracted HFD-induced downregulation of IL-10 and upregulation of pro-inflammatory markers in the mouse brain, both at gene and protein levels.

Discussion: This is the first report describing that a peptide from plant origin robustly restrained the pro-inflammatory activation of microglial cells in cultures and in brain. Our data suggest that GPETAFLR might be instrumental in maintaining CNS homeostasis by inhibiting neuroinflammation.

GRAPHICAL ABSTRACT

KEYWORDS:

• GPETAFLR peptide
• BV-2 cell line
• neuroinflammation
• cytokines
• high-fat diet
• bioactive
• protein hydrolysates
• Lupinus angustifolius‌

Acknowledgements

The authors thank Cell Biology Unit at the Instituto de la Grasa for its assistance during the fulfilment of this study. SMP acknowledges financial support from ‘V Own Research Plan’ (University of Seville).

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethics approval

All animal protocols received appropriate institutional approval (Animal Care and Use Committee of the University of Seville, AGL2012-40247-C02) and were performed according to the official rules formulated in the Spanish law on the care and use of experimental animals (UE Directive of 2010: 2010/63/UE; RD 53/2013).

Additional information

Funding

This work was supported by grants AGL2012-40247-C02 and CYTED -2019 119RT0567 from The Spanish Ministry of Science, Innovation and Universities.

Notes on contributors

Ana Lemus-Conejo

Ana Lemus-Conejo is a Predoctoral Student of the Spanish National Research Council at the Instituto de la Grasa, Seville, Spain. She received her master degree in Biomedicine at the School of Medicine, University of Seville. Her research is devoted to the cellular and molecular mechanisms by which nutrients affect health and disease.

Maria del Carmen Millan-Linares

Maria del Carmen Millan-Linares is the Head of the Cell Biology Unit of the Spanish National Research Council at the Instituto de la Grasa, Seville, Spain. She received her doctoral degree at the Pablo de Olavide University. Her research is devoted to the evaluation and production of high value protein products from agricultural byproducts applied to human health.

Rocio Toscano

Rocio Toscano is a Predoctoral Student of the Spanish National Research Council at the Instituto de la Grasa, Seville, Spain. Her research is devoted to the cellular and molecular mechanisms by which nutrients affect health and disease.

Francisco Millan

Francisco Millan is Scientific Investigator of the Spanish National Research Council at the Instituto de la Grasa, Seville, Spain. He received his doctoral degree in Chemistry at the University of Seville. His research is devoted to the evaluation and production of high value protein products from agricultural byproducts applied to human health.

Justo Pedroche

Justo Pedroche is Tenured Scientific of the Spanish National Research Council at the Instituto de la Grasa, Seville, Spain. He received his doctoral degree in Biology at the University of Seville. His research is devoted to the evaluation and production of high value protein products from agricultural byproducts applied to human health.

Francisco J. G. Muriana

Francisco J.G. Muriana is Scientific Investigator of the Spanish National Research Council at the Instituto de la Grasa, Seville, Spain. He received his doctoral degree in Biochemistry at the University of Seville. His research is devoted to the cellular and molecular mechanisms by which nutrients affect health and disease.

Sergio Montserrat-de la Paz

Sergio Montserrat-de la Paz is Professor in Biochemistry at the School of Medicine, University of Seville, and he received his doctoral degree at the same University. His research is devoted to the molecular and immunological-related mechanisms by which nutrients affect cardiometabolic diseases.