Inhibitory Effects of Ferulic Acid on Acetylcholine- and Platelet-Activating Factor-Induced Contractions in Guinea Pig Urinary Bladder Smooth Muscle

Abstract

Ferulic acid (FA), a hydroxycinnamic acid derivative abundantly present in the cell walls of cereal brans such as rice bran, has recently been suggested to suppress detrusor overactivity when administered orally. However, to the best of our knowledge, its direct inhibitory effects on urinary bladder smooth muscle (UBSM) contractions have not been investigated to date. In this study, we investigated the effects of FA on guinea pig UBSM contractions induced by two physiologically and pathophysiologically relevant agonists—acetylcholine (ACh, 10 µM) and platelet-activating factor (PAF, 1 µM)—and explored the underlying mechanisms. FA (0.3–3 mM) inhibited both ACh- and PAF-induced contractions in a concentration-dependent manner, with near-complete inhibition observed at 3 mM. These contractions were also nearly completely inhibited by diltiazem (10 µM), a selective L-type Ca²⁺ channel (LCC) blocker. FA similarly suppressed KCl-induced contractions in a concentration-dependent manner, which were almost completely abolished by diltiazem. The extent of inhibition by FA and diltiazem was generally consistent across all three stimuli. The calculated pIC₅₀ values of FA for the three types of contractions were approximately 3 (2.91 for ACh, 3.22 for PAF, and 3.05 for KCl). These findings indicate that FA strongly and non-selectively inhibits UBSM contractions induced by both physiological and pathophysiological stimuli, likely through blockade of LCCs and/or associated intracellular signaling pathways.