title: Scutellarin exerts its anti-hypertrophic effects via suppressing the Ca2+-mediated calcineurin and CaMKII signaling pathways.
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 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.
authors.affiliation: Department of Pharmacology, Harbin Medical University, Baojian Road 157, Harbin, Heilongjiang 150081, People's Republic of China.
authors.forename: Zhen-Wei
authors.initials: ZW
authors.lastname: Pan
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Dong-Hua
authors.initials: DH
authors.lastname: Mei
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.forename: Jing-Hao
authors.initials: JH
authors.lastname: Wang
authors.forename: Xiang-Ying
authors.initials: XY
authors.lastname: Zhang
authors.forename: Chang-Qing
authors.initials: CQ
authors.lastname: Xu
authors.forename: Yan-Jie
authors.initials: YJ
authors.lastname: Lu
authors.forename: Bao-Feng
authors.initials: BF
authors.lastname: Yang
mesh_terms: 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
chemical_list: 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