Bacopa monnieri supplementation has no effect on serum brain-derived neurotrophic factor levels but beneficially modulates nuclear factor kappa B and cyclic AMP response element-binding protein levels in healthy elderly subjects

假马齿苋补充剂对健康老年受试者的血清脑源性神经营养因子水平没有影响,但有益地调节核因子 κB 和环磷酸腺苷反应元件结合蛋白的水平

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作者:Andrew P Keegan, Con Stough, Daniel Paris, Cheryl A Luis, Laila Abdullah, Ghania Ait-Ghezala, Fiona Crawford, Michael Mullan

Aim

Bacopa monnieri is an Ayurvedic herb that has been used for multiple conditions, most notably to augment cognition, particularly memory and attention. Multiple mechanisms, including raising brain-derived neurotrophic factor (BDNF), have been proposed and investigated in animal models that require translational studies in humans.

Conclusion

These results suggest that Bacopa may exert an anti-inflammatory effect through NF-κB and improve intracellular signaling processes associated with synaptogenesis (CREB). The future placebo-controlled studies are recommended. Relevance for patients: B. monnieri will require larger, blinded trials to better understand potential mechanisms, interactions, and utilization.

Methods

Bacopa was administered in an open-labeled study to cognitively healthy controls over a 3-month period. Cognition and mood were assessed using the Montreal Cognitive Assessment (MoCA) and geriatric depression scale (GDS) at the baseline and 3-month visit. Laboratories were assessed for safety and serum levels of mature (mBDNF) and proBDNF were quantified. In a subset of subjects, intracellular signaling processes were assessed using western blot analysis.

Results

Bacopa was provided to 35 subjects and was well-tolerated except for 4 (11%) subjects who early terminated due to known, reversible, and gastrointestinal side effects (i.e., nausea, diarrhea). Over the 3 months, the GDS and the total MoCA did not significantly change; however, the delayed-recall subscale significantly improved (baseline: 3.8 ± 1.2, 3-months: 4.3 ± 0.9; P = 0.032). Serum mBDNF and proBDNF levels did not significantly change. Cyclic AMP response element-binding protein (CREB) phosphorylation significantly increased (P = 0.028) and p65 nuclear factor kappa B (NF-κB) phosphorylation significantly decreased (P = 0.030).

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