Abstract
Scutellarin is a flavonoid extracted from a traditional Chinese herb, Erigeron breviscapus Hand Mazz, which has been broadly used in treating various cardiovascular diseases. In this study, we investigated its effect on cardiac hypertrophy and the underlying mechanism. Both in vitro and in vivo cardiac hypertrophy models were employed to explore the anti-hypertrophic action of scutellarin. We found that scutellarin significantly suppressed the hypertrophic growth of neonatal cardiac myocytes exposed to phenylephrine (PE) and mouse heart subjected to pressure overload induced by aortic banding, accompanied with the decreased expression of hypertrophic markers β-myosin heavy chain and atrial natriuretic peptide. We then measured the change of free intracellular calcium using laser scanning confocal microscope. We found that scutellarin alleviated the increment of free intracellular calcium during cardiac hypertrophy either induced by PE or aortic banding. The expression of calcium downstream effectors calcineurin and phosphorylated calmodulin kinase II (CaMKII) were significantly suppressed by scutellarin. Our study indicated that scutellarin exerts its anti-hypertrophic activity via suppressing the Ca2+-mediated calcineurin and CaMKII pathways, which supports the observation that clinical application of scutellarin is beneficial for cardiovascular disease patients.
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Acknowledgements
This work was supported by the China Postdoctoral Science Foundation (to Zhen-Wei Pan), the National Natural Science Foundation of China (Grant No. 30971252; to Yan-Jie Lu), and the National Basic Research Program of China (973 Program; 2007CB512000/2007CB512006; to Bao-Feng Yang).
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Zhen-Wei Pan and Ying Zhang have equal contributions to the work.
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Pan, ZW., Zhang, Y., Mei, DH. et al. Scutellarin exerts its anti-hypertrophic effects via suppressing the Ca2+-mediated calcineurin and CaMKII signaling pathways. Naunyn-Schmied Arch Pharmacol 381, 137–145 (2010). https://doi.org/10.1007/s00210-009-0484-y
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DOI: https://doi.org/10.1007/s00210-009-0484-y