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Nutrients
Volume 17
Issue 8
10.3390/nu17081331
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Article

TOTUM-854 Human Circulating Bioactives Preserve Endothelial Cell Function

by
Fabien Wauquier
1,
Doriane Ripoche
2,
Line Boutin-Wittrant
1,
Yolanda F. Otero
2,
Stéphanie Krisa
3,
Josep Valls
4,
Mahéva Maura
5,
Florian Le Joubioux
5,
Thierry Maugard
6,
Gaëtan Bolea
7,
Grégory Meyer
7,
Cyril Reboul
7,
Véronique Roux
8,
Nicolas Macian
8,
Gisèle Pickering
8,
Bruno Pereira
9,
Maxime Bargetto
5,
Véronique Sapone
5,
Murielle Cazaubiel
5,
Sébastien Peltier
5,
Pascal Sirvent
2 and
Yohann Wittrant
1,10,*add Show full author list remove Hide full author list
1
Clinic’n’Cell SAS, Faculté de Médecine, 28 Place Henri Dunant, 63001 Clermont-Ferrand, France
2
Valbiotis, 20 rue Henri et Gilberte Goudier, 63200 Riom, France
3
INRAE, INP, Campus ISVV, Université de Bordeaux-INRAE-INP-ISVV, 210 Chem. de Leysotte, 33140 Villenave-d’Ornon, France
4
MetaboHUB, Bordeaux Metabolome, 210 Chem. de Leysotte, 33140 Villenave-d’Ornon, France
5
Valbiotis, Zone Industrielle des 4 Chevaliers, Bâtiment 12F, Rue Paul Vatine, 17180 Perigny, France
6
CNRS, LIENs, Campus NA, La Rochelle Université CNRS-LIENSs-, 2, Rue Olympe de Gouges, 17000 La Rochelle, France
7
LAPEC EA-4278, Avignon Université, 228 Route de L’Aérodrome, 84000 Avignon, France
8
CIC INSERM 1405/Plateforme d’Investigation Clinique CHU Gabriel Montpied, 63000 Clermont-Ferrand, France
9
Biostat Unit, DRCI, CHU, 63000 Clermont-Ferrand, France
10
INRAE, UMR 1019, UNH, 63000 Clermont-Ferrand, France
*
Author to whom correspondence should be addressed.
Nutrients 2025, 17(8), 1331; https://doi.org/10.3390/nu17081331
Submission received: 28 January 2025 / Revised: 6 March 2025 / Accepted: 4 April 2025 / Published: 11 April 2025
(This article belongs to the Special Issue Nutraceuticals, Bioactive Compounds and Functional Foods: Their Role in Chronic Diseases)
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Abstract

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.
Keywords: clinical trial; ex vivo; hypertension; plant extract; oxidative stress; lipotoxic stress; human metabolites; human endothelial cells clinical trial; ex vivo; hypertension; plant extract; oxidative stress; lipotoxic stress; human metabolites; human endothelial cells
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MDPI and ACS Style

Wauquier, F.; Ripoche, D.; Boutin-Wittrant, L.; Otero, Y.F.; Krisa, S.; Valls, J.; Maura, M.; Le Joubioux, F.; Maugard, T.; Bolea, G.; et al. TOTUM-854 Human Circulating Bioactives Preserve Endothelial Cell Function. Nutrients 2025, 17, 1331. https://doi.org/10.3390/nu17081331

AMA Style

Wauquier F, Ripoche D, Boutin-Wittrant L, Otero YF, Krisa S, Valls J, Maura M, Le Joubioux F, Maugard T, Bolea G, et al. TOTUM-854 Human Circulating Bioactives Preserve Endothelial Cell Function. Nutrients. 2025; 17(8):1331. https://doi.org/10.3390/nu17081331

Chicago/Turabian Style

Wauquier, Fabien, Doriane Ripoche, Line Boutin-Wittrant, Yolanda F. Otero, Stéphanie Krisa, Josep Valls, Mahéva Maura, Florian Le Joubioux, Thierry Maugard, Gaëtan Bolea, and et al. 2025. "TOTUM-854 Human Circulating Bioactives Preserve Endothelial Cell Function" Nutrients 17, no. 8: 1331. https://doi.org/10.3390/nu17081331

APA Style

Wauquier, F., Ripoche, D., Boutin-Wittrant, L., Otero, Y. F., Krisa, S., Valls, J., Maura, M., Le Joubioux, F., Maugard, T., Bolea, G., Meyer, G., Reboul, C., Roux, V., Macian, N., Pickering, G., Pereira, B., Bargetto, M., Sapone, V., Cazaubiel, M., ... Wittrant, Y. (2025). TOTUM-854 Human Circulating Bioactives Preserve Endothelial Cell Function. Nutrients, 17(8), 1331. https://doi.org/10.3390/nu17081331

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