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Bioavailability and Cardiovascular Action of Black Pitanga (*Eugenia uniflora L. var. Rubra Mattos*) and Grumixama (*Eugenia Brasiliensis*) Microbial Metabolites

¹ZANDONA, L. R.; ²BERNI, P. R. A.; ³MONFOULET, L-E.; ³MORAND, C.; ³MERCIER, S.; ³SIVIERI, K.; ⁴OLIVEIRA, F. L.; ¹MARÓSTICA JUNIOR, M. R.

**Keywords:** Bioactive Compounds; Metabolites; Cardiovascular (3 words)

**Summary:** Polyphenols, classified as flavonoids and non-flavonoids, are plant metabolites with significant physiological effects, particularly in protecting against chronic diseases such as cardiovascular conditions. Numerous studies highlight the cardiometabolic benefits of high polyphenol intake, which may involve increased nitric oxide (NO) production, reduced lipid circulation and deposition, delayed atherosclerosis,

<footnote n="1">¹Food Science and Nutrition Department, Faculty of Food Engineering, The State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil, l203129@dac.unicamp.br</footnote>

<footnote n="2">²Food Science and Nutrition Department, Federal University of the State of Rio de Janeiro (UNIRIO), Rio de Janeiro, Brazil, pberni@unirio.br</footnote>

<footnote n="3">³Research Team NutriVasc – “Diet, Plant Food Bioactives & Vascular Health”, INRAE – Université Clermont Auvergne, Saint-Genès-Champanelle, France, laurent-emmanuel.monfoulet@inrae.fr</footnote>

<footnote n="4">⁴Graduate Program in Food, Nutrition, and Food Engineering, Campus Araraquara, São Paulo State University (UNESP), Araraquara, Brazil, fellipe.lopes@unesp.br</footnote>
and enhanced endothelial function. However, further research is needed to fully
understand their mechanisms.

This study aimed to examine the in vitro metabolism of anthocyanins from black pitanga and grumixama, and their effects on endothelial function, simulating conditions of cardiometabolic disease. Anthocyanins were subjected to in vitro digestion (INFOGEST protocol) and fermentation (48-hour SHIME protocol) to simulate human microbiota interactions, and microbial metabolites were analyzed by LC-DAD-MS/MS. Endothelial effects were assessed using human endothelial cells (HUVECs), focusing on inflammation-related gene expression via RT-qPCR.

Results showed that total polyphenol concentrations were lowest in control samples. Using extracts and different microbiota types yielded varying polyphenol levels, with higher concentrations of ellagic acid in samples fermented with eutrophic microbiota (PE: 7.89 nmol/g, GE: 4.04 nmol/g) compared to obese microbiota (PE: 0.63 nmol/g, GE: 0.69 nmol/g). Viability assays on HUVECs indicated that non-fermented controls maintained viability above 80%, while ferments with microbiota exhibited high cytotoxicity. Samples fermented with obese microbiota led to lower cell viability, suggesting a more inflammatory profile.

Additionally, endothelial function improved with fruit and extract treatments, as indicated by lower TNF-α and adhesion molecules (ICAM and VCAM) in HUVECs. Grumixama showed greater efficacy in reducing TNF-α and adhesion markers in the obese microbiota context, whereas pitanga was more effective with eutrophic microbiota.

In conclusion, black pitanga and grumixama demonstrate potential for endothelial improvement, though further studies are needed to confirm efficacy.

This study was financed in part by the CNPq (307314/2023-5; 403976/2021-9; 301496/2019-6) and FAPESP (2022/09493-9, 2023/17076-1)