hydroxysafflor-yellow-a and Cardiomegaly

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.

Topics: Angiotensin II; Animals; Cardiomegaly; Cell Line; Chalcone; Disease Models, Animal; Heme Oxygenase-1; Male; Myocardial Infarction; NAD(P)H Dehydrogenase (Quinone); NF-E2-Related Factor 2; Protective Agents; Quinones; Rats; Rats, Sprague-Dawley; Signal Transduction

Hydroxysafflor yellow A (HSYA), the main chemical component of the safflower yellow pigments, is used extensively in traditional Chinese medicine for the treatment of cerebrovascular and cardiovascular diseases.. The present study determined the effects of HSYA on left ventricular hypertrophy after pressure overload and investigated the underlying mechanisms.. Cardiac hypertrophy was induced by the ligation of abdominal aorta in male Wistar rats. The rats were then divided into five groups and treated with captopril (100 mg/kg) or HSYA at different doses (0, 10, 20 and 40 mg/kg). Six weeks after treatment, the weight of left ventricle, LVMI (left ventricular mass index) and pathological changes were measured. MMP-2 (metalloproteinase 2) and MMP-9 (metalloproteinase 9) levels were determined by ELISA. Protein expressions of Bcl-2 and Bax were evaluated by immunohistochemistry.. HSYA (20, 40 mg/kg) significantly attenuated the increase of LVMI (ventricular weight/body weight) by 13.04 and 30.43% respectively, when compared with the model group. This was associated with the amelioration of pathological lesion, such as cardiac muscle fibers were smaller and the nuclei of cardiomyocytes were lightly stained in animals treated with HSYA (20, 40 mg/kg). In addition, the administration of HSYA at doses of 20 and 40 mg/kg increased the Bcl-2/Bax ratio (1.17 ± 0.08 and 1.39 ± 0.07 versus 0.71 ± 0.06). In addition, the serum MMP-2 and MMP-9 levels were blocked by the treatment at doses of 20 and 40 mg/kg HSYA (MMP-2, 76.1 ± 9.2 and 65.6 ± 6.8 versus 82.9 ± 6.2, ng/ml; MMP-9, 66.6 ± 4.8 and 57.5 ± 5.0 versus 83.5 ± 6.0, ng/ml).. These findings indicated that HSYA has beneficial effects on hypertensive ventricular remodeling, which may involve mechanisms of inhibiting cell apoptosis and suppressing metalloproteinases expression.

Topics: Animals; Apoptosis; Captopril; Cardiomegaly; Carthamus tinctorius; Chalcone; Disease Models, Animal; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Hypertension; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Medicine, Chinese Traditional; Myocytes, Cardiac; Quinones; Rats; Rats, Wistar; Ventricular Remodeling