Piezo1 channel inhibition by carvacrol in rat pulmonary smooth muscle cells - 09/05/26

Pulmonary hypertension (PH) is characterized by an increase in mean pulmonary arterial pressure above 20 mmHg at rest, driven by arterial wall remodeling, oxidative stress, and impaired calcium homeostasis in smooth muscle cells. The stretch-activated calcium channel Piezo1 plays a key role in this pathophysiology and represents a potential therapeutic target. Carvacrol, a natural monoterpene found in essential oils of aromatic plants such as thyme and oregano, is known for its vasorelaxant and antioxidant properties and has been proposed as a treatment for vascular disorders. In this study, we investigated the effect of carvacrol on Piezo1-mediated cellular responses.

Rat intrapulmonary arterial vascular smooth muscle cells were cultured under normoxic (19% O ₂ ) or hypoxic (1% O ₂ ) conditions for 48 hours to mimic the PH environment. Intracellular calcium concentration [Ca ²⁺ ]i, transmembrane potential, and reactive oxygen species (ROS) levels were assessed using fluorescent probes: Cal520 and FLIPR for [Ca ²⁺ ]i and membrane potential, respectively, and H ₂ DCFDA for ROS detection.

Under normoxic conditions, short-term exposure to carvacrol (50–300 μM, 3 min) induced a slight increase in basal [Ca ²⁺ ]i and membrane potential. However, it significantly inhibited Yoda1-induced [Ca ²⁺ ]i elevation and membrane depolarization. Under hypoxic conditions, carvacrol exhibited stronger inhibition of Yoda1 responses ([Ca ²⁺ ]i, membrane depolarization) and a marked reduction in Piezo1-mediated ROS production. Prolonged incubation with carvacrol (0.01–10 μM, 48 hours) consistently inhibited Piezo1-induced calcium responses, depolarization, and oxidative stress under both normoxic and hypoxic conditions.

In summary, carvacrol attenuates Piezo1-mediated increases in [Ca ²⁺ ]i, membrane depolarization, and oxidative stress, suggesting its potential as a therapeutic adjunct in the treatment of PH.