Hyperoside Protects Against Pressure Overload-Induced Cardiac Remodeling via the AKT Signaling Pathway

Abstract

Background/Aims: Cardiac hypertrophy is a major predisposing factor for heart failure and sudden cardiac death. Hyperoside (Hyp), a flavonoid isolated from Rhododendron ponticum L., is a primary component of Chinese traditional patent medicines. Numerous studies have shown that Hyp exerts marked anti-viral, anti-inflammatory, anti-oxidant, anti-cancer, anti-ischemic, and particularly cardio-protective effects. However, the effects of Hyp on cardiac hypertrophy have not been explored. The aims of this study were to determine whether Hyp could protect against cardiac remodeling and to clarify the potential molecular mechanisms. Methods: Neonatal rat cardiac myocytes were isolated and treated with different concentrations of Hyp, then cultured with angiotensin II for 48 h. Mice were subjected to either aortic banding or sham surgery (control group). One week after surgery, the mice were treated with Hyp (20 mg/kg/day) or vehicle by oral gavage for 7 weeks. Hypertrophy was evaluated by assessing morphological changes, echocardiographic parameters, histology, and biomarkers. Results: Hyp pretreatment suppressed angiotensin II-induced hypertrophy in cardiomyocytes. Hyp exerted no basal effects but attenuated cardiac hypertrophy and dysfunction, fibrosis, inflammation, and oxidative stress induced by pressure overload. Both in vivo and in vitro experiments demonstrated that the effect of Hyp on cardiac hypertrophy was mediated by blocking activation of the AKT signaling pathway. Conclusion: Hyp improves cardiac function and prevents the development of cardiac hypertrophy via AKT signaling. Our results suggest a protective effect of Hyp on pressure overload-induced cardiac remodeling. Taken together, Hyp may have a role in the pharmacological therapy of cardiac hypertrophy.

Exosomal circHIPK3 Released from Hypoxia-Pretreated Cardiomyocytes Regulates Oxidative Damage in Cardiac Microvascular Endothelial Cells via the miR-29a/IGF-1 Pathway

“…CMs were obtained [30] by using previously published methods. Immunofluorescence staining showed that the CMs expressed cTnT (Figure 1(a)).…”

“…Primary cultures of neonatal mouse CMs were prepared as previously described [30] with minor modifications. Briefly, 1- to 2-day-old mice were euthanized after performing heparinization for 5-10 min.…”

A Modified Formulation of Sutaehwan Ameliorates Menopausal Anxiety, Depression and Heart Hypertrophy in the VCD-Induced Menopausal Mouse Model

“…Among them, hyperoside prevents ageassociated renal injury through inhibition of autophagic activity by mammalian target of rapamycin (mTOR)-independent and AMPK-autophagy activating kinase 1 (ULK1) signaling pathways. 31) Moreover, hyperoside improves cardiac function and prevents the development of cardiac hypertrophy, 32) suggesting that STH_KP17001 may suppress VCD-induced cardiac hypertrophy via hyperoside-induced AMPK inhibition.…”

Hyperoside Attenuates Bleomycin-Induced Pulmonary Fibrosis Development in Mice

“…Additionally, Hyp was found to have a protective effect on chronic liver fibrosis induced through carbon tetrachloride (Zou et al, 2017). Moreover, Hyp could protect against cardiac remodeling induced by pressure overload through the inhibition of AKT signaling (Wang et al, 2018). In the present study, we explored the protective effects of Hyp on Blm-induced pulmonary fibrosis in a C57BL/6 mice model.…”