Insight into the Mechanisms Underlying the Tracheorelaxant Properties of the Sideritis raeseri Extract

Sideritis raeseri Boiss. and Heldr. (Lamiaceae), known as "mountain tea," is a native plant from the Mediterranean region, which is widely used in traditional medicine. This study evaluates the effects of the ethanol extract of Sideritis raeseri (SR) on airway smooth muscle activity and identifies the underlying mechanism. The S. raeseri extract (SRE) was extracted from air-dried parts of the shoot system of SR. The SRE (0.3-2 mg/mL) was tested in isolated rabbit tracheal rings, suspended in the organ bath, filled with Krebs solution, and bubbled with the carbogen mixture (95% O₂/5% CO₂) under a resting tension of 1 g in 37°C. In in vitro experiments, the SRE relaxed against acetylcholine-induced constriction in tracheal rings. Furthermore, SRE inhibited Ca²⁺-induced contractions in carbachol (CCh, 1 μM) as well as in the K⁺-depolarized trachea (80 mM). Our findings showed the NO/cGMP involvement in tracheorelaxant effects of SR. To this end, the effect of the SRE was potentiated by bradykinin (nitric oxide (NO) synthase activator, 100 nM), whereas it was inhibited by ODQ (inhibitor of NO-sensitive guanylyl cyclase, 10 μM) and L-NAME (NO synthase inhibitor, 100 μM), as well as indomethacin (cyclooxygenase inhibitor, 10 μM). These data suggest that the tracheorelaxant effect of the SRE is mediated at least partly by NO/cyclic guanosine monophosphate and cyclooxygenase-1-prostaglandin E2-dependent signaling. These findings indicate that the SRE may be used in various respiratory disorders.