Flavonoids as Anxiolytics in Animal Tests: Systematic Review, Meta-Analysis, and Bibliometrical Analysis

Area of Science:

• Pharmacology
• Neuroscience
• Natural Products Chemistry

Background:

• Flavonoids, plant-derived polyphenols, exhibit diverse neurophysiological effects.
• Some flavonoids demonstrate potential anxiolytic properties, prompting preclinical investigation.
• Anxiety disorders represent a significant area of unmet medical need, driving research into novel therapeutic agents.

Purpose of the Study:

• To comprehensively assess the anxiolytic potential of flavonoids using bibliometric analysis and systematic review with meta-analysis.
• To identify research trends, collaboration patterns, and knowledge gaps in the field of flavonoid anxiolytics.
• To provide evidence-based recommendations for future preclinical research on flavonoid-based anxiolytics.

Main Methods:

• Bibliometric analysis of publications on flavonoids and anxiety.
• Systematic review of 38 preclinical studies involving 43 different flavonoid molecules.
• Meta-analysis of 183 comparisons from animal tests (rats, mice, zebrafish) to quantify anxiolytic effects.

Main Results:

• Bibliometric analysis revealed research concentration in the Global South and identified key research themes.
• Meta-analysis demonstrated a significant overall anxiolytic-like effect of flavonoids (SMD = -1.457).
• Anxiolytic effects were evident in acute treatment but not consistently in chronic treatment; study quality was moderate.

Conclusions:

• Flavonoids possess significant anxiolytic-like properties in preclinical animal models.
• The field would benefit from increased international collaboration and more mechanistic research.
• Recommendations are provided to guide future preclinical studies on the anxiolytic potential of flavonoids.