Oxysterols and TLR-mediated intestinal inflammation: protective effect of cocoa bean shells. a smart way for waste valorisation

Dietary oxysterols’ability to induce intestinal inflammation is widelyknown. Considering the important role of Toll-like receptors (TLRs) inmediating immune and inflammatory responses, we verified if a mixtureof oxysterols widely present in cholesterol-rich foods could require TLR2and TLR4 activation to promote intestinal inflammation. Furthermore,the protective effects of cocoa bean shell (CBS) extracts with high poly-phenolic content were also investigated.Differentiated CaCo-2 enterocyte-like cells were treated with a dietaryoxysterol mixture and TLR2/4 gene expression and activation wereanalysed. Inflammation was evaluated by quantifying IL-8, IFNβandTNFαcell release. Honduras CBS polyphenolic fractions (HFs) werecharacterized by HPLC-DAD-MS/MS. The HF anti-inflammatory effectswere evaluated in cells under oxysterol mixture treatment.We observed that TLR2 and TLR4 activation is required to mediateoxysterol pro-inflammatory effects. HF pre-treatments fully preventedthe oxysterol-dependent cytokine induction, as well as TLR2/4 over-expression. These effects may be due to the high (-)-epicatechin andtannin quantities present in specific HFs.In conclusion, TLR2 and TLR4 can definitely contribute to mediateoxysterol pro-inflammatory action on intestinal cells. CBS fractions couldbe employed as anti-inflammatory food supplements, thus representingan important industrial design for recycling.