Wauquier Fabien, Ripoche Doriane, Boutin-Wittrant Line, Otero Yolanda F, Krisa Stéphanie, Valls Josep, Maura Mahéva, Le Joubioux Florian, Maugard Thierry, Bolea Gaëtan, Meyer Grégory, Reboul Cyril, Roux Véronique, Macian Nicolas, Pickering Gisèle, Pereira Bruno, Bargetto Maxime, Sapone Véronique, Cazaubiel Murielle, Peltier Sébastien, Sirvent Pascal, Wittrant Yohann
Clinic'n'Cell SAS, Faculté de Médecine, 28 Place Henri Dunant, 63001 Clermont-Ferrand, France.
Valbiotis, 20 rue Henri et Gilberte Goudier, 63200 Riom, France.
Nutrients. 2025 Apr 11;17(8):1331. doi: 10.3390/nu17081331.
: 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. : 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). : HUVEC protection against lipotoxicity was characterized by (1) decreased ACE-1 activity (-32% < 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, < 0.01); and (3) the inhibition of an inflammatory response, with a decrease in IL-1β release (-37% compared to palmitate, < 0.001) and decreased MCP-1 and VCAM-1 gene expression (-93% < 0.001 and -77% < 0.001, respectively). : 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.
TOTUM-854是一种获得专利的植物提取物混合物，其成分先前已被描述具有限制高血压发病的潜在健康益处。然而，大多数文献数据在细胞水平的作用模式方面仍为描述性内容，尤其是在人体中，需要进一步研究以优化治疗策略。我们首先在L-NAME小鼠模型中证明，TOTUM-854在体外和体内均有助于预防高血压。然后，我们设计了一种体外临床创新方法，考虑人体摄入TOTUM-854后消化道产生的循环代谢物。在健康志愿者急性摄入3.71 g TOTUM-854之前和之后收集人血清。通过超高效液相色谱-质谱法确认并表征了循环代谢物的生物利用度。含有TOTUM-854衍生代谢物的人血清进一步处理后，在不存在或存在棕榈酸（200 µM）的情况下与人内皮细胞（HUVECs）一起孵育。通过以下方式表征HUVEC对脂毒性的保护作用：（1）ACE-1活性降低（-32%，P<0.0001）；（2）通过DCFDA和DHE荧光显微镜观察到ROS降低（-12%）以及Nox2基因表达降低（与棕榈酸相比变化-6.7倍，P<0.01）来抑制氧化应激；（3）通过IL-1β释放减少（与棕榈酸相比-37%，P<0.001）以及MCP-1和VCAM-1基因表达降低（分别为-93%，P<0.001和-77%，P<0.001）来抑制炎症反应。总体而言，本研究提供了有关TOTUM-854在人内皮细胞中的保护作用的有见地的数据。使用创新的体外临床方法，我们的数据支持TOTUM-854循环代谢物在人体血管保护中的作用。
