Abstract
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.
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Abbreviations
- β-AR:
-
β-Adrenergic receptor
- JAK2:
-
Janus kinase 2
- STAT3:
-
Signal transducer and activator of transcription 3
- ISO:
-
Isoproterenol
- PCA:
-
Protocatechuic aldehyde
- ANF:
-
Atrial natriuretic factor
- β-MHC:
-
Beta-myosin heavy chain
- GADPH:
-
Glyceraldehyde-3-phosphate dehydrogenase
- NRCMs:
-
Neonatal rat cardiomyocytes
- CMC-Na:
-
Sodium carboxymethyl cellulose
- IVS:
-
Interventricular septum
- LVID:
-
Left ventricular internal diameter
- LVPW:
-
Left ventricular posterior wall thickness
- LVEF:
-
Left ventricular ejection fraction
- LVFS:
-
Left ventricular fractional shortening
- HW:
-
Heart weight
- BW:
-
Body weight
- LVW:
-
Left ventricular weight
- TL:
-
Tibia length
- HE:
-
Hematoxylin-eosin
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Funding
This work was supported by grants from the National Natural Science Foundation of China (No. 81072641, 81273499, 81473205, 81400359, 81673433, and 81200096), the Team item of the Natural Science Foundation of Guangdong Province (No. S2011030003190), the Major Project of Guangdong Provincial Department of Science and Technology (No. 2013B090700010), the Major Project of Platform Construction Education Department of Guangdong Province (No. 2014GKPT002), and the Special Program for Applied Science and Technology of Guangdong Province (No. 2015B020232009).
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XF, JY, and PL designed and conducted the experiments. HH, JY, YZ, and PW partially performed some experiments. XF, JY, YL, and JL analyzed the data and wrote the manuscript. All authors read and approved the manuscript.
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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. This article does not contain any studies with human participants performed by any of the authors. All animal experiments were performed in accordance with the Guide for the Care and Use of Laboratory Animals by the National Institutes of Health (USA) and approved by the Research Ethics Committee of Sun Yat-sen University (No. 017962).
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Fang, X., Liu, Y., Lu, J. et al. Protocatechuic aldehyde protects against isoproterenol-induced cardiac hypertrophy via inhibition of the JAK2/STAT3 signaling pathway. Naunyn-Schmiedeberg's Arch Pharmacol 391, 1373–1385 (2018). https://doi.org/10.1007/s00210-018-1556-7
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DOI: https://doi.org/10.1007/s00210-018-1556-7