Phytoestrogen calycosin-7-O-β-D-glucopyranoside ameliorates advanced glycation end products-induced HUVEC damage

Abstract

Vasculopathy including endothelial cell (EC) apoptosis and inflammation contributes to the high incidence of stroke and myocardial infarction in diabetic patients. The aim of the present study was to investigate the effect of calycosin-7-O-β-D-glucopyranoside (CG), a phytoestrogen, on advanced glycation end products (AGEs)-induced HUVEC damage. We observed that CG can significantly ameliorate AGEs-induced HUVEC oxidative stress and apoptosis. The ratio of SOD/MDA was significantly increased to the normal level by CG pretreatment. CG preincubation dramatically increased anti-apoptotic Bcl-2 while decreased pro-apoptotic Bax and Bad expressions as detected by immunocytochemistry. Moreover, CG ameliorated macrophage migration and adhesion to HUVEC; the monocyte chemotactic protein-1 and interleukin-6 levels in the culture supernatant were dramatically reduced by CG as determined by ELISA; the expressions of inflammatory proteins including ICAM-1, TGF-β1, and RAGE in both protein and mRNA levels were significantly reduced to the normal level by CG pretreatment as determined by immunocytochemistry and real-time RT-PCR. The intracellular investigation suggests that CG can reverse AGEs-activated ERK1/2 and NF-κB phosphorylation, in which estrogen receptors were involved in. Our results strongly indicate that CG can modulate EC dysfunction by ameliorating AGEs-induced cell apoptosis and inflammation.

Heparanase induced by advanced glycation end products (AGEs) promotes macrophage migration involving RAGE and PI3K/AKT pathway

“…In agreement with previous study [26,37], we have shown that AGEs induced macrophage migration significantly. However, more importantly, we have shown that pretreatment of anti-HPA antibody, which bind to the C-terminus domain of HPA specially, inhibited the macrophage migration significantly (Figure 2).…”

“…Monocytes transmigrate into the subendothelial space and differentiate into macrophages, which migrate, infiltrate and accumulate in the vascular tissues, involving in diabetic vascular complications. Clinical study has also observed significant increase of AGEs accumulation in diabetic vascular tissues [25], which may induce macrophage migration across an endothelial cell monolayer [26]. …”

Anti-Inflammation effects of Radix Astragali Plays an Important Role in Ameliorating Type 2 Diabetes Mellitus

“…Flavonoids, which are abundant in RA as discussed above [25], have been demonstrated to protect cells from OS damage [39]. It has been reported from us and other research groups that calycosin has protective effect in endothelial cells against hypoxia-induced barrier impairment [40], and calycosin-7-O-β-D-glucosidehas free radicals scavenging activity [41] and it could significantly ameliorate AGEs-induced cell OS and apoptosis in a concentration-dependent manner [32,41].…”

“…Advanced glycation end products (AGEs), which were the key initiator and promoter of T2DM, have been demonstrated to be a class of NF-κB-involved inflammation activators [31]. Recently, we also found and reported that calycosinand calycosin-7β-D-glucoside could significantly decrease inflammatory cytokines secretion, inhibit macrophage inhibition and ameliorate AGEsinduced NF-κB activation in human umbilical vein endothelial cells (HUVECs) [32,33].…”

Role of Advanced Glycation End Products in the Progression of Diabetes Mellitus

“…It is demonstrated that hyperglycemia itself can contribute to OS by forming glycation products that propagate free radicals and enlarge oxidative damage [10]. Moreover, OS itself can induce free radical damage to the DNA and fi nally promote cell apoptosis [11]; furthermore, OS may directly and indirectly up-regulate infl ammatory proteins expression and exaggerate diabetic infl ammation.…”