Bioflavonoids and vasoactive mediator release from mast cells

Area of Science:

• Pharmacology
• Natural Product Chemistry
• Inflammation Research

Background:

• Flavonoids are plant-derived compounds with diverse biological activities.
• Anti-inflammatory properties of flavonoids are of significant therapeutic interest.
• Understanding the dose-dependent effects of flavonoids is crucial for their application.

Purpose of the Study:

• To investigate the anti-inflammatory and cardiovascular effects of 5-hydroxy and 7-hydroxy flavones.
• To elucidate the mechanism of action, particularly the role of mast cells.
• To determine the dose-dependent effects of these flavones on inflammation and physiological responses.

Main Methods:

• Carrageenan-induced pedal inflammation model in rats.
• Assessment of inotropic effect on isolated frog atria.
• In vitro and in vivo studies on rat mesenteric mast cells.
• Evaluation of mast cell degranulation induced by flavones and compound 48/80.
• Local paw injection of 7-hydroxy flavone to induce edema.

Main Results:

• 5-hydroxy and 7-hydroxy flavones attenuated carrageenan-induced inflammation at lower doses, but this effect diminished at higher doses.
• These flavones exhibited a positive inotropic effect on frog atria, which was reversible and blocked by indomethacin.
• Both compounds induced mast cell degranulation in vitro and in vivo at higher concentrations/doses.
• Lower concentrations/doses of flavones inhibited compound 48/80-induced mast cell degranulation, while higher concentrations/doses did not.
• High-dose 7-hydroxy flavone injection into rat paws caused significant edema.

Conclusions:

• 5-hydroxy and 7-hydroxy flavones possess a biphasic action on mast cells, acting as stabilizers at low concentrations and degranulators at high concentrations.
• This biphasic activity influences their anti-inflammatory and pro-inflammatory effects.
• The findings highlight the importance of dose in determining the pharmacological outcomes of these flavones.