Protective Effect of Hydroxysafflor Yellow A on Nephropathy by Attenuating Oxidative Stress and Inhibiting Apoptosis in Induced Type 2 Diabetes in Rat

Abstract

Diabetic nephropathy (DN) is a serious complication of diabetes mellitus, and its prevalence has been increasing all over the world, which is also the leading cause of end-stage renal failure. Hydroxysafflor yellow A (HSYA) is the main active chemical component of Carthamus tinctorius L., and it is commonly used in patients with cardiovascular and cerebrovascular diseases in China. The aim of this study was to investigate the renal protective effects and molecular mechanisms of HSYA on high-fat diet (HFD) and streptozotocin- (STZ-) induced DN in rats. The DN rats were treated with HSYA for eight weeks. We assessed creatinine (CR), urea nitrogen (UN), glomerular volume, podocyte number, renal inflammation, oxidative stress, and cells apoptosis markers after HSYA treatment. The number of apoptotic cells was measured by the TUNEL assay, and apoptosis-related proteins BAX, caspase-3, and BCL-2 in the renal tissue were analyzed by western blot. The treatment with HSYA significantly decreased fasting blood glucose, CR, UN, and blood lipid profile, including triglyceride and total and low-density lipoprotein cholesterol, even though it did not change the rats’ body weights. The western blot results indicated that HSYA reversed the upregulation of BAX and caspase-3 and significantly increased BCL-2 in renal tissue. Moreover, the levels of TNF-α and the inflammatory products, including free fatty acids (FFA) and lactic dehydrogenase (LDH) in the HSYA group, were significantly decreased. For the oxidative stress marker, the superoxide dismutase (SOD) markedly increased in the HSYA treatment group, while the malondialdehyde (MDA) in the serum and kidney tissue evidently decreased. In conclusion, HSYA treatment preserved kidney function in diabetic nephropathy in the HFD- and STZ-induced rats. The potential mechanism of renal protective effect of HSYA might be through inhibiting oxidative stress, reducing inflammatory reaction, and attenuating renal cell apoptosis. Our studies present a promising use for Hydroxysafflor yellow A in the treatment of type 2 diabetes mellitus.

Protective Effects of Two Safflower Derived Compounds, Kaempferol and Hydroxysafflor Yellow A, on Hyperglycaemic Stress-Induced Podocyte Apoptosis via Modulating of Macrophage M1/M2 Polarization

“…Traditional Chinese medicine (TCM) has already shown its effects in treating DN proteinuria and was able to provide a variety of effective renoprotective extracts [ 4 ]. In recent years, kaempferol (Ka) and hydroxysafflor yellow A (HSYA), two active components of safflower, attracted attention for their roles in ameliorating diabetes-induced fibrosis and renal damage [ 5 , 6 ]. Safflower yellow injection (SYI), which contains more than 90% HSYA, is recommended by TCM experts for clinical treatment of DN in China [ 7 ].…”

Burdock Fructooligosaccharide Attenuates High Glucose-Induced Apoptosis and Oxidative Stress Injury in Renal Tubular Epithelial Cells

“…In this study, we aimed to study the protective effect of BFO on NRK-52E cell apoptosis and oxidative stress induced by HG. Although the exact mechanism of HG-induced renal tubular epithelial cell injury has not yet been fully clarified, researches have shown that oxidative stress and apoptosis play important roles in the development and pathogenesis of DN ( Tiong et al, 2019 ; Lee et al, 2020 ). NRK-52E cells cultured with HG are widely used as a DN model ( Hou et al, 2014 ; Slyne et al, 2015 ).…”

Bu-Shen-Huo-Xue Decoction Ameliorates Diabetic Nephropathy by Inhibiting Rac1/PAK1/p38MAPK Signaling Pathway in High-Fat Diet/Streptozotocin-Induced Diabetic Mice

“…Furthermore, these data suggest a direction for exploring the individual components of BSHX decoction. As a main chemical component of Carthami Flos , Hydroxysafflor yellow A has been demonstrated to be able to reduce high glucose-induced pancreatic β-cells apoptosis via PI3K/AKT and JNK/c-Jun signaling pathways ( Zhao et al, 2018 ; Lee et al, 2020a ), and exerts a renal protective effect by inhibiting oxidative stress, reducing inflammatory responses, and attenuating renal cell apoptosis in rats with a HFD- and STZ-induced diabetes ( Lee et al, 2020b ). Loganin, a major chemical component of Corni Fructus , had the highest concentration in the medicated serum in this study, and exerts an early renal protective role in DN by inhibiting connective tissue growth factor ( Jiang et al, 2012 ), and alleviating the loss of podocytes induced by high glucose via targeting AGEs-RAGE and its downstream pathways, p38MAPK and Nox4, in vivo or in vitro ( Chen et al, 2020 ).…”