Dioscin ameliorates cardiac hypertrophy through inhibition of the MAPK and Akt/GSK3β/mTOR pathways

Liang Chen; Qingnian Li; Lei Lei; Tianyu Li

doi:10.1016/j.lfs.2018.08.039

Dioscin ameliorates cardiac hypertrophy through inhibition of the MAPK and Akt/GSK3β/mTOR pathways

Life Sci. 2018 Sep 15:209:420-429. doi: 10.1016/j.lfs.2018.08.039. Epub 2018 Aug 17.

Authors

Liang Chen¹, Qingnian Li², Lei Lei³, Tianyu Li⁴

Affiliations

¹ Division of Cardiology, Department of Internal Medicine and Gene Therapy Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Huazhong University of Science and Technology, Hubei Province, Wuhan 430030, China.
² Department of Emergency Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
³ Division of Cardiology, Department of Internal Medicine and Gene Therapy Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Huazhong University of Science and Technology, Hubei Province, Wuhan 430030, China. Electronic address: [email protected].
⁴ Department of Traumatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: [email protected].

PMID: 30125581
DOI: 10.1016/j.lfs.2018.08.039

Abstract

Cardiac hypertrophy occurs in response to multiple stimuli and develops into congestive heart failure with morbidity and mortality. Dioscin exerts protective effects against tumor growth and ischemia/reperfusion injury. However, whether and how dioscin attenuates angiotensin II (AngII)-induced cardiac hypertrophy is still unknown. In the current study, we found that dioscin attenuated cardiac hypertrophy and restored the impaired cardiac function induced by AngII infusion in vivo. In addition, dioscin blocked the activation of the MAPK and Akt/GSK3β/mTOR pathways and nuclear accumulation of p-Akt1 in AngII-infused mice. In vitro, dioscin inhibited the activation of the MAPK and Akt/GSK3β/mTOR pathways and nuclear translocation of p-Akt1 and thus alleviated the hypertrophic growth. Our study demonstrated dioscin protects against AngII-induced cardiac hypertrophy via inhibition of the MAPK and Akt/GSK3β/mTOR pathways and is a potential therapeutic candidate.

Keywords: Akt1; Angiotensin II; Cardiac hypertrophy; Dioscin; MAPK.

MeSH terms

Angiotensin II / toxicity
Animals
Cardiomegaly / chemically induced
Cardiomegaly / drug therapy*
Cardiomegaly / metabolism
Diosgenin / analogs & derivatives*
Diosgenin / pharmacology
Glycogen Synthase Kinase 3 beta / antagonists & inhibitors*
Glycogen Synthase Kinase 3 beta / genetics
Glycogen Synthase Kinase 3 beta / metabolism
Male
Mice
Mice, Inbred C57BL
Mitogen-Activated Protein Kinases / antagonists & inhibitors*
Mitogen-Activated Protein Kinases / genetics
Mitogen-Activated Protein Kinases / metabolism
Proto-Oncogene Proteins c-akt / antagonists & inhibitors*
Proto-Oncogene Proteins c-akt / genetics
Proto-Oncogene Proteins c-akt / metabolism
TOR Serine-Threonine Kinases / antagonists & inhibitors*
TOR Serine-Threonine Kinases / genetics
TOR Serine-Threonine Kinases / metabolism
Vasoconstrictor Agents / toxicity

Substances

Vasoconstrictor Agents
Angiotensin II
dioscin
mTOR protein, mouse
Akt1 protein, mouse
Glycogen Synthase Kinase 3 beta
Gsk3b protein, mouse
Proto-Oncogene Proteins c-akt
TOR Serine-Threonine Kinases
Mitogen-Activated Protein Kinases
Diosgenin