Scutellarin exerts its anti-hypertrophic effects via suppressing the Ca2+-mediated calcineurin and CaMKII signaling pathways.
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 beta-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 Ca(2+)-mediated calcineurin and CaMKII pathways, which supports the observation that clinical application of scutellarin is beneficial for cardiovascular disease patients.
Pan
Zhen-Wei
ZW
Department of Pharmacology, Harbin Medical University, Baojian Road 157, Harbin, Heilongjiang 150081, People's Republic of China.
Zhang
Ying
Y
Mei
Dong-Hua
DH
Zhang
Rui
R
Wang
Jing-Hao
JH
Zhang
Xiang-Ying
XY
Xu
Chang-Qing
CQ
Lu
Yan-Jie
YJ
Yang
Bao-Feng
BF
D000818:Animals; D000831:Animals, Newborn; D047310:Apigenin / Q000494:pharmacology* / Q000627:therapeutic use; D019703:Calcineurin / Q000096:biosynthesis*; D002118:Calcium / Q000502:physiology*; D020013:Calcium Signaling; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000096:biosynthesis / Q000502:physiology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D006332:Cardiomegaly / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use; D005965:Glucuronates / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use
D004365:Drugs, Chinese Herbal; D005965:Glucuronates; D014665:Vasodilator Agents; C484876:scutellarin; D010656:Phenylephrine; D047310:Apigenin; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019703:Calcineurin; D002118:Calcium