Myricetin Possesses Potential Protective Effects on Diabetic Cardiomyopathy through Inhibiting IκBαNFκB and Enhancing Nrf2HO-1

Abstract EN

Diabetic cardiomyopathy (DCM) is associated with a greater risk of mortality in patients with diabetes mellitus.

Currently, no specific treatment has been suggested for DCM treatment.

This study demonstrated that myricetin (M) attenuated DCM-associated cardiac injury in mice subjected to streptozotocin (SZT) and in neonatal rat cardiomyocytes (NRCM) challenged with high glucose.

In vivo investigation demonstrated 6 months of M treatment (200 mg/kg/d) significantly alleviated cardiac hypertrophy, apoptosis, and interstitial fibrosis.

Mechanically, M treatment significantly increased the activity of Nrf2/HO-1 pathway, strengthening antioxidative stress capacity evidenced by reversed activities of GPx and SOD, and decreased MDA production.

M treatment also inhibited IκBα/NF-κB pathway, resulting in reduced secretion of inflammation cytokines including IL-1β, TNF-α, and IL-6.

Besides, the TGFβ/Smad3 signaling was also blunted in DCM mice treated with M.

These beneficial effects of M treatment protected cardiomyocytes from apoptosis as shown by decreased TUNEL-positive nucleus, c-caspase 3, and Bax.

Similar effects of M treatment could be reproduced in NRCM treated with high glucose.

Furthermore, through silencing Nrf2 in NRCM, we found that the regulation of IκBα/NFκB by M was independent on its function on Nrf2.

Thus, we concluded that M possesses potential protective effects on DCM through inhibiting IκBα/NFκB and enhancing Nrf2/HO-1.