Journal Article

TOTUM-854 Human Circulating Bioactives Preserve Endothelial Cell Function

Wittrant, Yohann, Sapone, Véronique, Otero, Yolanda F., Boutin-Wittrant, Line, Pereira, Bruno, Cazaubiel, Murielle, Bolea, Gaëtan, Peltier, Sébastien, Wauquier, Fabien, Ripoche, Doriane, Maura, Mahéva, Le Joubioux, Florian, Pickering, Gisèle, Macian, Nicolas, Valls, Josep, Meyer, Grégory, Roux, Véronique, Maugard, Thierry, Reboul, Cyril, Bargetto, Maxime, Sirvent, Pascal, Krisa, Stéphanie

2025

Overview

Background: TOTUM-854 is a patented plant extract blend characterized by its components that have previously been described for their potential health benefits in limiting hypertension onset. However, most of the literature data remain descriptive regarding the mode of action at the cellular level, especially in humans, and further investigations are required for optimized therapeutic strategies. Methods: We first demonstrated in an L-NAME mouse model that TOTUM-854 supports the prevention of hypertension in vitro and in vivo. Then, we designed an ex vivo clinical innovative approach considering the circulating metabolites produced by the digestive tract upon TOTUM-854 ingestion in humans. Human serum was collected in healthy volunteers before and after the acute intake of 3.71 g of TOTUM-854. The bioavailability of circulating metabolites was confirmed and characterized by UPLC-MS. Human serum containing TOTUM-854-derived metabolites was further processed for incubation with human endothelial cells (HUVECs), in the absence or presence of palmitate (200 µM). Results: HUVEC protection against lipotoxicity was characterized by (1) decreased ACE-1 activity (−32% p < 0.0001); (2) the inhibition of oxidative stress with decreased ROS (−12% observed by DCFDA and DHE fluorescent microscopy) and decreased Nox2 gene expression (−6.7 fold change vs. palmitate, p < 0.01); and (3) the inhibition of an inflammatory response, with a decrease in IL-1β release (−37% compared to palmitate, p < 0.001) and decreased MCP-1 and VCAM-1 gene expression (−93% p < 0.001 and −77% p < 0.001, respectively). Conclusions: Overall, this study provides insightful data regarding the protective role of TOTUM-854 in human endothelial cells. Using an innovative clinical ex vivo approach, our data support the role of TOTUM-854 circulating metabolites in vascular protection in humans.

• Publisher: MDPI AG,MDPI
• Subject: Acids / Adult / Analysis / Animals / Biological products / Blood pressure / Chemical Sciences / Drinking water / Endothelial Cells - drug effects / Endothelium / Engineering Sciences / Enzymes / Ethics / Female / Health aspects / Human Umbilical Vein Endothelial Cells - drug effects / Human Umbilical Vein Endothelial Cells - metabolism / Humans / Hypertension / Hypertension - prevention & control / Immune system / Inflammation / Life Sciences / Male / Metabolites / Mice / NADPH Oxidase 2 - genetics / NADPH Oxidase 2 - metabolism / Nutrition research / Oxidative stress / Oxidative Stress - drug effects / Plant Extracts - blood / Plant Extracts - pharmacokinetics / Plant Extracts - pharmacology / Polyphenols / Reactive Oxygen Species - metabolism