Relaxing effect of Sideritis raeseri Boiss. & Heldr. on the uterus is dependent on calcium and nitric oxide signaling pathways

Context: Sideritis raeseri Boiss. & Heldr. (Lamiaceae), commonly known as “mountain tea,” is a medicinal plant with a long-standing use in traditional medicine. Aims: To evaluate the effects of Sideritis raeseri ethanol extract (SRE) on uterine smooth muscle contractility and elucidate its underlying mechanisms of action. Methods: An ethanol extract was prepared from the aerial parts of SRE. Isolated rabbit uterine rings were suspended in organ baths containing physiological salt solution at 37°C, continuously bubbled with 95% O₂ and 5% CO₂. The relaxant effects of SRE (0.5–2 mg/mL) were assessed on spontaneous and induced uterine contractions. Uterine contractions were stimulated using carbachol (1 µM), high K⁺ (80 mM), oxytocin (5 nM), or indomethacin (10 µM). The involvement of Ca²⁺ influx and NO/cGMP signaling was investigated using L-NAME (100 µM, NO synthase inhibitor) and bradykinin (100 nM, NO synthase activator). Results: SRE significantly inhibited spontaneous uterine contractions in a concentration-dependent manner. It also reduced Ca²⁺-induced contractions under all tested stimuli. The relaxant effect was attenuated by L-NAME and enhanced by bradykinin, suggesting the involvement of NO-mediated pathways. Conclusions: These results indicate that the uterine relaxant activity of SRE involves both calcium modulation and NO-dependent signaling pathways. SRE shows potential as a natural tocolytic agent for the management of uterine hyperactivity or related disorders.