Open AccessCrocetin protects against cardiac hypertrophy by blocking MEK‐ERK1/2 signalling pathway
Author(s) -
Cai Jun,
Yi FangFang,
Bian ZhouYan,
Shen DiFei,
Yang Long,
Yan Ling,
Tang QiZhu,
Yang XinChun,
Li Hongliang
Publication year - 2009
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2008.00620.x
Subject(s) - crocetin , muscle hypertrophy , oxidative stress , mapk/erk pathway , chemistry , kinase , protein kinase a , p38 mitogen activated protein kinases , medicine , endocrinology , biology , pharmacology , biochemistry , carotenoid
Oxidative stress plays a critical role in the progression of pathological cardiac hypertrophy and heart failure. Because crocetin represses oxidative stress in vitro and in vivo , we have suggested that crocetin would repress cardiac hypertrophy by targeting oxidative stress‐dependent signalling. We tested this hypothesis using primary cultured cardiac myocytes and fibroblasts and one well‐established animal model of cardiac hypertrophy. The results showed that crocetin (1–10 μM) dose‐dependently blocked cardiac hypertrophy induced by angiogensin II (Ang II; 1 μM) in vitro . Our data further revealed that crocetin (50 mg/kg/day) both prevented and reversed cardiac hypertrophy induced by aortic banding (AB), as assessed by heart weight/body weight and lung weight/body weight ratios, echocardio‐graphic parameters and gene expression of hypertrophic markers. The inhibitory effect of crocetin on cardiac hypertrophy is mediated by blocking the reactive oxygen species (ROS)‐dependent mitogen‐activated protein kinase (MAPK)/extracellular signal‐regulated kinase‐1/2 (MEK/ERK1/2) pathway and GATA binding protein 4 (GATA‐4) activation. Further investigation demonstrated that crocetin inhibited inflammation by blocking nuclear factor kappa B (NF‐κB) signalling and attenuated fibrosis and collagen synthesis by abrogating MEK‐ERK1/2 signalling. Overall, our results indicate that crocetin, which is a potentially safe and inexpensive therapy for clinical use, has protective potential in targeting cardiac hypertrophy and fibrosis by suppression of ROS‐dependent signalling pathways.