Send to

Choose Destination
Oxid Med Cell Longev. 2019 Dec 6;2019:6304058. doi: 10.1155/2019/6304058. eCollection 2019.

Myricetin Alleviates Pathological Cardiac Hypertrophy via TRAF6/TAK1/MAPK and Nrf2 Signaling Pathway.

Liao HH1,2, Zhang N1,2, Meng YY1,2, Feng H3, Yang JJ1,2, Li WJ1,2, Chen S2, Wu HM2, Deng W1,2, Tang QZ1,2.

Author information

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China.
Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan, Hubei 430060, China.
Department of Geriatrics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China.


Myricetin (Myr) is a common plant-derived polyphenol and is well recognized for its multiple activities including antioxidant, anti-inflammation, anticancer, and antidiabetes. Our previous studies indicated that Myr protected mouse heart from lipopolysaccharide and streptozocin-induced injuries. However, it remained to be unclear whether Myr could prevent mouse heart from pressure overload-induced pathological hypertrophy. Wild type (WT) and cardiac Nrf2 knockdown (Nrf2-KD) mice were subjected to aortic banding (AB) surgery and then administered with Myr (200 mg/kg/d) for 6 weeks. Myr significantly alleviated AB-induced cardiac hypertrophy, fibrosis, and cardiac dysfunction in both WT and Nrf2-KD mice. Myr also inhibited phenylephrine- (PE-) induced neonatal rat cardiomyocyte (NRCM) hypertrophy and hypertrophic markers' expression in vitro. Mechanically, Myr markedly increased Nrf2 activity, decreased NF-κB activity, and inhibited TAK1/p38/JNK1/2 MAPK signaling in WT mouse hearts. We further demonstrated that Myr could inhibit TAK1/p38/JNK1/2 signaling via inhibiting Traf6 ubiquitination and its interaction with TAK1 after Nrf2 knockdown in NRCM. These results strongly suggested that Myr could attenuate pressure overload-induced pathological hypertrophy in vivo and PE-induced NRCM hypertrophy via enhancing Nrf2 activity and inhibiting TAK1/P38/JNK1/2 phosphorylation by regulating Traf6 ubiquitination. Thus, Myr might be a potential strategy for therapy or adjuvant therapy for malignant cardiac hypertrophy.

Supplemental Content

Full text links

Icon for Hindawi Limited Icon for PubMed Central
Loading ...
Support Center