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Plantamajoside Attenuates Isoproterenol-Induced Cardiac Hypertrophy Associated With the HDAC2 and AKT/ GSK-3β Signaling Pathway

Plantamajoside Attenuates Isoproterenol-Induced Cardiac Hypertrophy Associated With the HDAC2 and AKT/ GSK-3β Signaling Pathway

Linlin Shang, Lv Pin, Shanshan Zhu, Xiaohang Zhong, Yubiao Zhang, Mao Shun, Yunen Liu, Mingxiao Hou

Chem Biol Interact. 2019 Jul 1;307:21-28.

PMID: 31009642

Abstract:

As a compensatory response to cardiac overload, cardiac hypertrophy is closely associated with the occurrence and development of a variety of cardiovascular diseases, in which histone deacetylase 2 (HDAC2) has been reported to play an important role. Plantamajoside (PMS) is an active component extracted from Herba Plantaginis, which is a traditional Chinese medicine, and many biological activities of PMS have been reported. Here, we investigated the effects and mechanism of PMS on isoproterenol (ISO)-induced cardiac hypertrophy. ISO at 10 μmol/L was used in vitro to induce H9c2 cardiomyocyte hypertrophy. Cell viability and cell surface area were determined by MTT assay and immunocytochemistry, respectively. Furthermore, an in vivo, cardiac hypertrophy model was established by subcutaneous injection of ISO. Pathological alterations and fibrosis in the myocardium were studied by H&E and Masson's trichrome staining, respectively. Myocardial injury-related genes and proteins were detected by real-time PCR and western blotting. HDAC2 and its downstream proteins, AKT and GSK3β, were analyzed by western blotting. Our results showed that, in vitro, PMS inhibited the ISO-induced increase in H9c2 cell surface area and the mRNA expression of ANP, BNP and Myh7. In vivo, PMS improved the ISO-induced decrease in cardiac function, inhibited the increase in cardiac anatomical parameters and alleviated the histopathological changes in cardiac tissues. Moreover, PMS inhibited the mRNA and protein expression of ANP, BNP, Myh7, COL1 and COL3. Furthermore, PMS suppressed the activity of HDAC2 and down-regulated the expression of the downstream proteins p-AKT and p-GSK3β both in vitro and in vivo. Overall, our results indicated that PMS exerts significant cardioprotective effects against ISO-induced cardiac hypertrophy, and this protective effect may be mediated by inhibition of the HDAC2 and AKT/GSK-3β signaling pathway.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP104777686	Plantamajoside		104777-68-6	Price

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