Acacetin improves endothelial dysfunction and aortic fibrosis in insulin-resistant SHR rats by estrogen receptors

Abstract

The aim of the work was to investigate the effects of acacetin on endothelial dysfunction and aortic fibrosis in insulin-resistant SHR rats and explore its mechanism. Seven-week-old male spontaneously hypertensive rats (SHR) were selected to establish a rat model of hypertension with insulin resistance induced by 10% fructose. The nuclear factor kappa B p65 (NF-κB p65) and Collagen I were observed by Immunohistochemistry. Immunofluorescence was used to observe estrogen receptor-alpha (ERα), estrogen receptor-beta (ERβ), and G protein-coupled receptor 30 (GPR30). Western blotting was used to detect interleukin (IL-1β), Arginase 2 (ARG2), Nostrin, endothelial nitric oxide synthase (eNOS), TGF-β, Smad3, ERK pathway proteins such as p-c-Raf, p-MEK1/2, p-ERK, ERK, p-P90RSK and p-MSK1. We found that acacetin did have an improvement on endothelial dysfunction and fibrosis. Meanwhile, it was also found to have a significant effect on the level of estrogen in this model by accident. Then, the experiment of uterine weight gain in mice confirmed that acacetin had a certain estrogen-like effect in vivo and played its role through the estrogen receptors pathway. In vitro experience HUVEC cells were stimulated with 30 mM/L glucose and 100 mM/L NaCl for 24 h to establish the endothelial cell injury model. HUVEC cells were treated with 1 μM/L estrogen receptors antagonist (ICI 182780) for 30 min before administration. Cell experiments showed that acacetin could reduce the apoptosis of HUVEC cells, the levels of inflammatory cytokines and the expression of TGF-β, Collagen I and Smad3 in endothelial cell injury model. After treatment with ICI 182780, the improvement of acacetin was significantly reversed. The results showed that acacetin relieved endothelial dysfunction and reduced the aortic fibrosis in insulin-resistant SHR rats by reducing the release of inflammatory factors and improving vasodilatory function through estrogen signaling pathway.

Transplantation of adipose-derived stem cells ameliorates Echinococcus multilocularis-induced liver fibrosis in mice

“…In recent years, anti-fibrotic mechanisms of ADSCs have been progressively elucidated [18,19]. TGF-β is one of the most classical and important signaling pathway in fibrosis pathogenesis, and its up-regulation activates hepatic stellate cells (HSCs), α-smooth muscle actin (α-SMA) expression, and the synthesis of ECM proteins, such as collagens [20]. Moreover, the TGF-β signaling pathway mediates the anti-fibrotic effects of ADSCs in diseases.…”

WITHDRAWN: Assessment Parameters on Array Pulse Wave Analysis and Application in Hypertensive Disorders

“…A large amount clinical and epidemiological evidence have indicated that hypertension is one of the major risk factors for cardiovascular disease, characterized by impaired vascular structure and endothelial function, which is the early vascular lesion of hypertension. [25] In this study, both SBP and DBP in the hypertension group were significantly higher than in the healthy group (Table 2). It has been explained in the previous studies that the increase of h1 and h3/h1 was associated with arterial stiffness.…”

“…To acquire a statistical analysis, we used SPSS 25.0 program to analyze the data. Two Independent Student T test and Mann-Whitney U test were applied for two group comparisons.…”

Assessment Parameters for Arrayed Pulse Wave Analysis and Application in Hypertensive Disorders

“…A large amount of clinical and epidemiological evidence indicates that hypertension is a major risk factor for cardiovascular disease and that it can be characterized by impaired vascular structure and endothelial function as indicators of early vascular lesions [ 27 ]. In this study, both SBP and DBP were significantly higher in the hypertensive group than in the healthy group ( Table 1 ).…”