Involvement of Cholinergic and Cyclooxygenase Pathways in the Diuretic Effects of Rosmarinic Acid

Rosmarinic acid (RA) is a natural antioxidant known for its diverse biological activities. Although its diuretic activity has been previously established, the mode of action remained unclear. To investigate this, we examined the diuretic activity of RA alone and in combination with hydrochlorothiazide (HCTZ), amiloride (AML), atropine (ATR), and indomethacin (INDO) to see if any of these drugs could interfere with RA's activity in an 8‐hour acute diuresis animal model. We observed that RA increases urine excretion and may have a synergistic effect in the HCTZ+RA group, with a potassium‐sparing capacity. In the AML+RA group, we also noted increased urine excretion while sodium and potassium excretion decreased. ATR and INDO prevented RA from increasing urine excretion, suggesting a potential interaction with muscarinic receptors or a role in promoting prostaglandin production. Additionally, molecular docking analysis indicated possible interactions with key receptors involved in increased diuresis or free‐electrolyte water excretion.