Citrus flavonoids stimulate secretion by human colonic T84 cells

Area of Science:

• Plant biochemistry
• Gastroenterology
• Cellular physiology

Background:

• Flavonoids are plant compounds found in many foods, including citrus fruits.
• Dietary intake of flavonoids is substantial, averaging 1 g daily.
• Their specific effects on the digestive system, particularly colonic secretion, are not well understood.

Purpose of the Study:

• To investigate the impact of specific citrus flavonoids on colonic secretion.
• To determine the mechanisms underlying flavonoid-induced changes in colonic secretion.

Main Methods:

• Utilized an in vitro model of colonic secretion using T84 cell monolayers in Ussing chambers.
• Administered polymethoxylated flavonoids (tangeretin, nobiletin) and glycosylated flavonoids (naringin, hesperidin) at 100 μmol/L.
• Assessed electrogenic chloride secretion by measuring short-circuit current.
• Investigated synergistic effects with carbachol and vasoactive intestinal peptide (VIP).
• Examined the role of cAMP pathway and reactive oxygen species (ROS).

Main Results:

• Tangeretin and nobiletin significantly stimulated electrogenic chloride secretion (maximal 3.3 μA/cm²).
• Naringin and hesperidin showed minimal secretory effects, indicating carbohydrate substitutions inhibit potential.
• Secretion stimulated by tangeretin and nobiletin was synergistic with carbachol but not VIP.
• Inhibition by barium chloride, bumetanide, H-89, and chloride depletion suggests involvement of the cAMP pathway.
• Flavonoids did not auto-oxidize, ruling out ROS mediation.

Conclusions:

• Dietary citrus flavonoids, specifically tangeretin and nobiletin, can modulate colonic secretion.
• These flavonoids likely interact directly with intracellular secretory pathways, potentially via the cAMP pathway.
• The presence or absence of carbohydrate substitutions significantly impacts the secretory potential of flavonoids.