Polyphenols as Modulators of Gastrointestinal Motility: Mechanistic Insights from Multi-Model Studies

Area of Science:

• Gastroenterology and Pharmacology
• Natural Product Chemistry

Background:

• Dietary polyphenols modulate gastrointestinal (GI) motility, with potential therapeutic benefits for conditions like irritable bowel syndrome and functional dyspepsia.
• Reported effects of polyphenols on GI motility are inconsistent, ranging from spasmolytic to prokinetic, necessitating a deeper understanding of their mechanisms.

Purpose of the Study:

• To synthesize experimental evidence on polyphenol structure-activity relationships and their mechanisms of action on GI motility.
• To clarify the heterogeneous effects of polyphenols on GI motility and identify patterns for therapeutic development.

Main Methods:

• Conducted a narrative review of publications from PubMed and Google Scholar on polyphenols and GI motility.
• Integrated findings from in vitro, ex vivo, in vivo, and clinical studies to analyze mechanisms and structure-activity relationships.

Main Results:

• Polyphenols act as multi-target modulators of GI smooth muscle, primarily by blocking L-type Ca2+ channels and activating K+ channels (BK, KATP).
• Flavones and flavonols show spasmolytic activity via Ca2+ channel antagonism, while flavanones induce hyperpolarization via BK and KATP channels.
• Complex plant extracts exhibit mixed effects due to diverse constituent compounds; dataset heterogeneity hinders direct clinical translation.

Conclusions:

• Polyphenols are multi-mechanistic modulators of GI motility with discernible structure-activity patterns.
• Future research should focus on standardized pharmacokinetics, targeted structure-activity studies, and rigorous clinical trials to advance clinical applications.