Protocatechuic aldehyde protects against isoproterenol-induced cardiac hypertrophy via inhibition of the JAK2/STAT3 signaling pathway

Protocatechuic aldehyde (PCA) is a natural compound found in the Chinese herb Salvia miltiorrhiza. It has been shown to possess multiple biological activities and to protect the cardiovascular system against oxidative stress, inflammation, and atherosclerosis. However, the potential effects of PCA on cardiac hypertrophy remain to be investigated. In this study, we showed that isoproterenol treatment (ISO, 10 μM for 24 h) induced significant hypertrophy in cultured neonatal rat cardiomyocytes, as manifested by enlargement of cell surface area (1.74-fold greater than that of the control, p < 0.05) and upregulation of hypertrophic gene markers (2.44- to 2.75-fold increase in ANF and β-MHC protein expression, p < 0.05). These ISO-induced hypertrophic responses were attenuated by PCA (50-200 μM, p < 0.05). Furthermore, intragastric administration of PCA (10-100 mg/kg/day) ameliorated cardiac hypertrophy in ISO-treated rats (1.5 mg/kg/day, s.c., for 7 days). PCA inhibited the abnormal changes in echocardiographic parameters and suppressed ISO-induced increase in cardiomyocyte cross-sectional area and collagen content (p < 0.05). It also ameliorated ISO-mediated elevation of HW/BW, LVW/BW, and HW/TL ratios (p < 0.05). Mechanistically, ISO facilitated JAK2 and STAT3 phosphorylation, increased STAT3 nuclear translocation, and enhanced STAT3 transcriptional activity. All these changes were attenuated by PCA. Taken together, these findings showed that PCA could protect against cardiac hypertrophy induced by ISO possibly via inhibition of the JAK2/STAT3 signaling pathway, suggesting the potential of PCA as a therapeutic candidate for hypertrophy-associated heart diseases.