1, 8-cineole Attenuates Cardiac Hypertrophy in Heart Failure by Inhibiting the MiR-206-3p/SERP1 Pathway

Background: 1,8-Cineole (1,8-CIN) is a monoterpene found in diverse dietary and medicinal herbs that has been reported to be effective against cardiovascular diseases.

Purpose: The present research was designed to elucidate the treatment effects and the underlying mechanism of 1,8-CIN on heart failure (HF).

Method: An in vitro cardiac hypertrophy model and an in vivo heart failure (HF) model induced by isoprenaline (ISO) were established and treated with or without 1,8-CIN. In vitro miR-206-3p mimic or inhibitors were created. MiR-206-3p, SERP1 and related mRNAs or proteins were detected using qPCR or western blotting. Cell viability was tested by MTT assay, and apoptosis was measured using TUNEL assay, AO/EB assay and flow cytometry. Actin was stained with FITC-phalloidin. MiR-206-3p and related mRNAs or proteins in cardiac muscle tissues were measured using qPCR or western blotting, HE staining, Masson staining.

Results: ISO subcutaneous injection increased cardiac hypertrophy, cytoplasmic vacuole formation, myofiber loss and fibrosis and decreased cardiomyocyte viability. 1,8-CIN treatment improved cardiomyocyte viability and reduced cardiac hypertrophy, cytoplasmic vacuole formation, myofibre loss and fibrosis. We found that 1,8-CIN attenuated apoptosis. We observed that expression of miR-206-3p was dramatically increased in ISO-exposed cardiomyocytes or ISO-treated rat hearts. MiR-206-3p was identified to target the 3'UTR of SERP1, resulting in the accumulation of un- or misfolded proteins, leading to endoplasmic reticulum (ER) stress.

Conclusion: These results suggest that 1,8-CIN reduces the apoptosis induced by ER stress through inhibiting miR-206-3p, which inhibits the expression of SERP1.