Identification, characterization, and molecular docking of immunomodulatory oligopeptides from bioavailable hempseed protein hydrolysates
2024
Millán Linares, María del Carmen | Rivero Pino, Fernando | González de la Rosa, Teresa | Villanueva, Álvaro | Montserrat de la Paz, Sergio | Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología | Instituto de Biomedicina de Sevilla (IBIS) | Universidad de Sevilla. CTS-1074: InmunoNutrición e InmunoMetabolismo | Plan Andaluz de Investigación, Desarrollo e Innovación | European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER)
Promoting dietary patterns in which the content of vegetables is higher than the current consumption of them is one of the strategies to achieve a sustainable food system while promoting health in humans. Hemp (Cannabis sativa L.) protein contains bioactive peptides that can be released via enzymatic hydrolysis. These peptides must reach the target organ in order to potentially exert bioactivity and regulate specific metabolic pathways. The peptides contained in two bioavailable hempseed protein hydrolysates (bioHPHs) showing anti-inflammatory activity were identified using a transwell system employing CACO-2 cell culture as absorption model and subjected to in silico analysis to select 10 unique peptides. These sequences were chemically synthetized to verify their activity in primary human monocytes (assessing gene expression of IL-1β, IL-6, TNF-α, IL-4, IL-10, and TLR4), in addition to evaluate the interaction with TRL4/MD2 by molecular docking. Six peptides (DDNPRRF, SRRFHLA, RNIFKGF, VREPVFSF, QADIFNPR and SAERGFLY) showed high immunomodulatory activity in in vitro and the mechanisms of interaction with TLR4/MD2 were described. Bioavailable anti-inflammatory hempseed-derived peptides were identified, and their activity verified, suggesting the health benefits that the ingestion of HPHs could exert in humans. These findings open new opportunities for developing nutritional strategies with hemp as a dietary source of biopeptides to prevent the development and progression of inflammatory-related diseases.
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