Modulatory effect of Andean blackberry polyphenols on genes related to antioxidant and inflammatory responses, the NLRP3 inflammasome, and autophagy

Article type: Research Article

Authors: Castejón-Vega, Beatriz^a | Kyriakidis, Nikolaos C.^b | Alcócer-Gómez, Elizabet^c | Giampieri, Francesca^{d; e} | González-Paramás, Ana M.^f | Cordero, Mario D.^{g; h; *} | Alvarez-Suarez, José M.^{i; j; *}

Affiliations: [a] Institute of Molecular, Cell and Systems Biology, University of Glasgow, Glasgow G12 8QQ, UK | [b] Cancer Research Group, Faculty of Medicine, Universidad de Las Américas, Quito, Ecuador | [c] Departamento de Psicología Experimental, Facultad de Psicología, Universidad de Sevilla, Seville, Spain | [d] Research Group on Food, Nutritional Biochemistry and Health, Universidad Europea del Atlántico, Santander, Cantabria, Spain | [e] Department of Clinical Sciences, Polytechnic University of Marche, Ancona, Italy | [f] Grupo de Investigación en Polifenoles, Universidad de Salamanca, Campus Miguel de Unamuno, Salamanca, Spain | [g] Instituto de Investigación e Innovación en Ciencias Biomédicas de Cádiz (INiBICA), Cádiz, Spain. | [h] CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain | [i] Laboratorio de Bioexploración. Universidad San Francisco de Quito USFQ, Quito, Ecuador | [j] Laboratorio de Investigación de Ingeniería en Alimentos (LabInAli). Colegio de Ciencias e Ingeniería, Universidad San Francisco de Quito USFQ, Quito, Ecuador

Correspondence: [*] Corresponding author: José M. Alvarez-Suarez, E-mail: [email protected] and Mario D. Cordero, E-mail: [email protected].

Abstract: BACKGROUND: The Andean blackberry (Rubus glaucus Benth) is one of Ecuador’s most iconic Andean berries for which a high anthocyanin content has been described. OBJECTIVE: The aim of the present study was to determine the chemical composition and anti-inflammatory potential of the Andean blackberry from Ecuador, with an emphasis on its effects on NLRP3 inflammasome activation and autophagy processes. RESULTS: Andean blackberry extracts were rich in hydroxycinnamates (coumaric acid and derivates), in addition to quercetin and kaempferol as principal flavonols. Cyanidin and its glycosides were identified as the main anthocyanins present. Andean blackberry extracts efficiently reduced oxidative stress markers in the lipopolysaccharide-stimulated RAW 264.7 cells. The extracts also caused a moderate decrease in the expression of the pro-inflammatory and antioxidant genes NFκB1, TNF, IL-1β, IL-6, and NOS2 expression, while they significantly increased the mRNA levels of both SOD1 and NFE2L2 genes. Andean blackberry extracts significantly decreased the activation of the NLRP3 inflammasome complex, as well as p62 levels, and the LC3I/LC3II ratio increased, suggesting a direct action of Andean blackberry compounds on the inflammatory response and restoration of the autophagy process. CONCLUSIONS:These results suggest that Andean blackberries potentially have an anti-inflammatory effect through their ability to regulate genes related to the inflammatory and antioxidant response, as well as modulate the activation of the NLRP3 inflammasome complex and autophagy processes.

Keywords: Anthocyanins, autophagy, blackberries, inflammation, NRLP3 inflammasome

DOI: 10.3233/JBR-230058

Journal: Journal of Berry Research, vol. 14, no. 1, pp. 41-59, 2024