Repurposing Bacopa monnieri extracts containing Aquaporin-1 blockers to improve systemic oxidative stress: The BacOxy_I study

Boughaleb, Hasnae;Verdoy, Roxane;Pochet, Amandine;Fabian, Nathalie;Montiel, Virginie;et.al.
(2025) Advances in Redox Research — Vol. 15, p. 100126 (2025)

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Abstract
Reactive oxygen species (ROS) Endothelial dysfunction Aquaporin 1 (AQP1) Bacopaside II Bacopa monnieri S U M M A R Y Objectives: To evaluate the efficacy of Bacopa monnieri (BM) containing Bacopaside II, a specific Aquaporin 1 (AQP1)-blocker, on systemic oxidative stress. Background: AQP1, is a peroxiporin which facilitates hydrogen peroxide transmembrane passage. It is predominantly expressed in endothelial cells and erythrocytes. Methods: BM extract was administered orally for 6 weeks to 20 healthy volunteers (Group A/B: 400/800 mg/ day). Assessments occurred at baseline (V0), after 6 weeks of treatment (V4), and 4 weeks post-treatment (V6). Primary endpoint: ROS levels in erythrocytes post-H 2 O 2 exposure (DCFDA fluorescence). Secondary endpoints: Oxidative stress and safety biomarkers, blood pressure monitoring. Bacopaside II metabolites in plasma were identified using liquid chromatography-mass spectrometry (LC-MS). Results: BM intake reduced ROS levels in RBCs in Group B (T40 min: Mean Fluorescence Intensity of DCF V0=381 ± 43 a.u vs V4= 187 ± 69 a.u, p<0.01). Methemoglobin and oxidized Methionine 148 of Apolipoprotein A-1 levels decreased (Methemoglobin group B: V0= 0.900 ± 0.105 a.u vs V4= 0.233 ± 0.047 a.u; p<0.001, M148-ox/M148 ratio group B: V0= 0.06 ± 0.01 a.u. vs V4= 0.02 ± 0.00 a.u.; p<0.05). A reduction in blood pressure was observed in Group B (Systolic Blood Pressure V0=131 ± 15 mmHg vs SBP V4=116 ± 7 mmHg; p < 0.05). Two potential Bacopaside II metabolites with putative binding pockets on AQP1 were identified during the treatment. Conclusion: A six-week oral intake of BM reduced systemic oxidative stress in healthy volunteers in a dose-dependent manner. Pharmacological blocking of AQP1 may help restore redox balance in the vasculature.
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Boughaleb, H., Verdoy, R., Pochet, A., Fabian, N., Bella, R., Muruganandam, G., Frédérick, R., Boudjeltia, K., Bourez, A., Delporte, C., Van Antwerpen, P., Robert, A., Haufroid, V., Dewulf, J., Balligand, J.-L., & Montiel, V. (2025). Repurposing Bacopa monnieri extracts containing Aquaporin-1 blockers to improve systemic oxidative stress: The BacOxy_I study. Advances in Redox Research, 15, 100126. https://doi.org/10.1016/j.arres.2025.100126 (Original work published 2025)