Hydroxysafflor yellow A protects against angiotensin II‑induced hypertrophy

Abstract

Myocardial infarction (MI) is life-threatening and is generally accompanied by myocardial hypertrophy. Notably, Hydroxysafflor yellow A (HSYA) can prevent tissue injuries. The objective of this study was to investigate the effect of HSYA on hypertrophy after MI. Hematoxylin and eosin (H&E) staining assays were performed to measure cell area. The protein synthesis rate was assessed using the 3H Leucine incorporation assay. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blot analysis and the immunohistochemical assay were used to detect the expression of target genes. The activity of superoxide dismutase (SOD), malondialdehyde (MDA) and the reactive oxygen species (ROS) generation were examined using commercial kits. Decreased myocardial hypertrophy was observed in animals treated with HSYA. Furthermore, the expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) was higher in HSYA administration groups compared with that in the MI model group. In H9c2 cardiomyocytes, the pretreatment with HSYA increased the cell viability, however, it reduced protein synthesis rate, mitigated cell surface area and decreased the expression of Brain natriuretic factor (BNP) and β-myosin heavy chain (β-MHC). By contrast, the downregulation of Nrf2 deteriorated and reversed the effect of Ang II and HSYA. Furthermore, oxidative stress was alleviated by HSYA via inhibiting ROS generation, modulating the activities of SOD and MDA. In addition, the expression of NAD(P)H:quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1) were recovered by the pretreatment of HSYA that was combated by siNrf2. In conclusion, HSYA exerted anti-hypertrophic effects, which was pertinent with the activation of Nrf2/NQO-1/HO-1 signaling pathway. The findings of this study may inspire a novel strategy to combat MI.

The Prevention Role of Theaflavin-3,3′-digallate in Angiotensin II Induced Pathological Cardiac Hypertrophy via CaN-NFAT Signal Pathway

“…In this study, ANGII was chosen to establish the PCH model, ANP and BNP mRNA levels increased significantly after 0.5 μM ANGII stimulation for 24 h. This may be caused by the inhibition of transcription and expression of natriuretic peptide receptor A (ANP and BNP receptors) [ 20 ]. In addition to ANP and BNP, the low-expression of the α-myosin heavy chain (α-MHC) and over-expression of the β-myosin heavy chain (β-MHC) gene expression were also observed in the PCH model [ 21 , 22 ].…”

“…Hyperactivity of MAPKs (JNK, P38, ERK) signal pathways can also be observed in PCH models and could result in transforming PCH to malignant heart failure [ 36 ]. Natural alkaloids berberine was proven to inhibit PCH through the AMPK pathway [ 21 ]. The CaN-NFAT signal pathway is regulated by Ca 2+ and is directly related to the expression of fetal genes.…”

Hydroxysafflor Yellow A Ameliorates Myocardial Ischemia/Reperfusion Injury by Suppressing Calcium Overload and Apoptosis

“…Carthamus tinctorius L. has been used for thousands of years, and its traditional applications include promoting blood circulation, clearing blood stasis, and relieving pain [31,32]. HSYA, one of the main active ingredients of Carthamus tinctorius L., has a flavonoid structure and excellent antioxidant activity [16,33].…”

Therapeutic Potential of Hydroxysafflor Yellow A on Cardio-Cerebrovascular Diseases

“…A specialized piece of in vivo research demonstrated that the antioxidant effect of HSYA was involved in the prevention of Ang II-induced myocardial hypertrophy (a compensatory response to MI), which may act through the activation of the nuclear factor erythroid-2-related factor 2 (Nrf2)/NAD(P)H: quinone oxidoreductase 1/HO-1 signaling pathway (Ni et al, 2018). Nrf-2, as the main regulator of the antioxidant system present on the cardiovascular system, is becoming a very promising pharmacological target for cardiovascular diseases (McSweeney et al, 2016).…”

“…Promotes endothelial progenitor cells function through the HO-1/VEGF-A/stromal cell-derived factor-1a signaling cascade (Wei et al, 2017) MI model in male SD rats 2, 5 mg•kg -1 i.p. Activates the Nrf2/NAD(P)H:quinone oxidoreductase 1/HO-1 signaling pathway (Ni et al, 2018) Ang II-induced H9c2 cells 80 mmol•L -1 / Increases the cell viability, however, reduces protein synthesis rate, mitigates cell surface area and decreases the expression of brain natriuretic factor and b-myosin heavy chain (Ni et al, 2018) Myocardial ischemia/ reperfusion (MI/ R) injury MI/R model in male SD rats 5 mg•kg -1 i.p. Decreases JAK2/signal transducer and activator of transcription 1 activity, enhances antioxidant capacity and decreases apoptosis (Zhou et al, 2019) Hyperlipidemia combined with MI/R model in male Wistar rats 8, 16, 32 mg•kg -1 i.p.…”