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

Abstract

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-H₂O₂ 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.