Neuroprotective effect of mealworm protein hydrolysate-derived bioactive peptides in human microglial cells

Abstract The larva of Tenebrio molitor , better known as mealworm, is one of the most studied insects today, since it was recently classified as safe for human consumption. Specifically, its high protein content makes it a splendid candidate for the search for bioactive peptides, with properties ranging from anti-inflammatory to neuroprotective. In this study, the effect of a digested hydrolysate on microglia cells (which previously demonstrated high anti-inflammatory activity in intestinal CACO-2 cells) was analysed, specifically on their levels of gene expression of various cytokines, such as IL-6, IL-10, or IL-1β, among others. In addition, four chemically synthesised peptides, selected from this digested hydrolysate based on in silico analysis, including the estimation of the bioactive properties of these peptides, their physicochemical properties and their toxicokinetic, were evaluated in the microglia cells as well. In addition, molecular docking assays of the peptides were performed with two receptors relevant to inflammation. Relevant changes in the expression of IL-6, IL-1β, and BDNF were observed due to the action of the peptides, especially in the case of IYVDAVIN and SLPSLPEPV. These results provide an insight on how specific peptides found in Tenebrio molitor could be used as therapeutics agent in the immunomodulation of brain cells.