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.