Apocynum Tablet Protects against Cardiac Hypertrophy via Inhibiting AKT and ERK1/2 Phosphorylation after Pressure Overload

Abstract

Background. Cardiac hypertrophy occurs in many cardiovascular diseases. Apocynum tablet (AT), a traditional Chinese medicine, has been widely used in China to treat patients with hypertension. However, the underlying molecular mechanisms of AT on the hypertension-induced cardiac hypertrophy remain elusive. The current study evaluated the effect and mechanisms of AT on cardiac hypertrophy. Methods. We created a mouse model of cardiac hypertrophy by inducing pressure overload with surgery of transverse aortic constriction (TAC) and then explored the effect of AT on the development of cardiac hypertrophy using 46 mice in 4 study groups (combinations of AT and TAC). In addition, we evaluated the signaling pathway of phosphorylation of ERK1/2, AKT, and protein expression of GATA4 in the cardioprotective effects of AT using Western blot. Results. AT inhibited the phosphorylation of Thr202/Tyr204 sites of ERK1/2, Ser473 site of AKT, and protein expression of GATA4 and significantly inhibited cardiac hypertrophy and cardiac fibrosis at 2 weeks after TAC surgery (P < 0.05). Conclusions. We experimentally demonstrated that AT inhibits cardiac hypertrophy via suppressing phosphorylation of ERK1/2 and AKT.

Cardioprotective Effects of Radix on the Pressure Overloaded Heart Failure Model by Transverse Aortic Constriction-induced Mice

“…Well corresponded to the previous studies 10,11) , significant increases of mortalities, heart weights, and hypertrophic, lytic and focal fibrotic histological changes in the left ventricles were found with defects of heart antioxidant defense systemsthe increases of heart cortex MDA contents, decreases of GSH contents, SOD and CAT activities in TAC control mice as compared with sham vehicle control mice, respectively. However, these HF signs induced by TAC surgery through PO and destroys of heart antioxidant defense systems were significantly and dose-dependently inhibited by 14 days continuous oral treatment of SMR 500, 250 and 125 mg/kg, respectively.…”

“…According to the previous TAC experiments 11,32) , survivability of animals from TAC surgery amounted to 60 ~ 80%, and also showed as 75.0% in TAC control mice in the present study. However, potent increases of survivabilities were detected by oral treatment of SMR 500, 250 and 125 mg/kg as 100.0, 100.0 and 87.5%, dose-dependently and also by resveratrol 10 mg/kg as 87.5%.…”

“…In the present study, the cardioprotective effects of SMR were evaluated on the PO induced HF by TAC in C57BL/6 mice 10,11) through possible antioxidant effects. The results were compared with resveratrol, in which potent cardioprotective effects on TAC mice model through antioxidant effects were already proved, as reference 10) .…”

“…Up to now, many experiments have indicated that SMR has potent antioxidant-based cardioprotective effects against various animal or in vitro models, mainly myocardial infarctions [7][8][9] , however, no study has examined the effects of SMR on preventing chronic pathological changes within cardiac structure and function in PO-induced HF in C57BL/6 mice. The objective of this study is to find out the cardioprotective effects of SMR on the PO-induced HF by TAC in C57BL/6 mice 10,11) with possible antioxidant effects. The changes on the mortality, body and heart weights, indicators of antioxidant defense system and histopathology of heart were investigated.…”

Salvianolic Acid B Alleviates Heart Failure by Inactivating ERK1/2/GATA4 Signaling Pathway after Pressure Overload in Mice

“…We constructed a mouse model of HF by TAC surgery to impose pressure overload, using a proven protocol that was published previously [8] . Similar TAC model was also used successfully by Sadoshima et al [9].…”