Relationship of the Phytochemicals from Coffee and Cocoa By-Products with their Potential to Modulate Biomarkers of Metabolic Syndrome In Vitro

This study aimed to compare the phytochemicals from coffee and cocoa by-products and their relationship with the potential for reducing markers of inflammation, oxidative stress, adipogenesis, and insulin resistance in vitro. We characterized the phytochemical profile of extracts from coffee husk, coffee silverskin, and cocoa shell and evaluated their in vitro biological activity in RAW264.7 macrophages and 3T3-L1 adipocytes. Pearson correlations and principal component regressions were performed to find the contribution of phytochemicals and underlying mechanisms of action. Coffee husk and silverskin extracts were mainly composed of caffeine and chlorogenic acid. Major components in cocoa shell included theobromine and protocatechuic acid. Both coffee and cocoa by-product extracts effectively reduced inflammatory markers in macrophages and adipocytes (NO, PGE₂, TNF-α, MCP-1, and IL-6) and the production of reactive oxygen species (21.5–66.4%). Protocatechuic and chlorogenic acids, together with caffeine, were suggested as main contributors against inflammation and oxidative stress. Furthermore, extracts reduced lipid accumulation (4.1–49.1%) in adipocytes by regulating lipolysis and inducing adipocyte browning. Gallic and chlorogenic acids were associated with reduced adipogenesis, and caffeine with adipocyte browning. Extracts from coffee and cocoa by-products also modulated the phosphorylation of insulin receptor signaling pathway and stimulated GLUT-4 translocation (52.4–72.9%), increasing glucose uptake. The insulin-sensitizing potential of the extracts was mainly associated with protocatechuic acid. For the first time, we identified the phytochemicals from coffee and cocoa by-products and offered new insights into their associations with biomarkers of inflammation, oxidative stress, adipogenesis, and insulin resistance in vitro.