Angelica sinensispolysaccharides inhibit endothelial progenitor cell senescence through the reduction of oxidative stress and activation of the Akt/hTERT pathway

Abstract

Context: Angelica sinensis (Oliv.) Diels (Apiaceae) polysaccharides (ASP) may play a key role in anti-ischemic activity. However, the anti-atherosclerotic activity and mechanism are unknown. Objective: This study investigated the protective effects of ASP against ox-LDL-induced senescence of EPCs and explored its underlying molecular mechanisms. Materials and methods: Mononuclear cells were isolated from bone marrow (BM) of SD rats and differentiated to EPCs. EPCs were exposed to oxidized low-density lipoprotein (ox-LDL, 10 mg/ mL, 24 h) and incubated with or without high-dose (100 mg/mL, 48 h) or low-dose (20 mg/mL, 48 h) ASP. Another group of EPCs was pre-treated with Wortmannin (100 nM, 45 min), a PI3K/ Akt inhibitor. EPC senescence, telomerase activity, and superoxide anion levels were assessed using SA-b-galactosidase staining, telomerase PCR-ELISA analysis, and DHE staining, respectively. The expression of related proteins, including Akt, p-Akt, hTERT, p-hTERT, and gp91phox, were detected using western blot. Results: EPCs (47.3%) were SA-b-gal positive after treatment by ox-LDL, additionally, ox-LDL significantly increased superoxide anion levels (375% versus 100%), and inhibited telomerase activity (42% versus 100%). However, the pro-senescent effect of ox-LDL was attenuated about three-fold (16.7%), superoxide anion levels were decreased more than two-fold (148%), and telomerase activity was recovered partly (88% versus 42%) in the EPCs when treated with ASP (100 mg/mL). The immunoblotting confirmed that ASP attenuated inhibition of phosphorylation of Akt and hTERT induced by ox-LDL and down-regulated increased the expression of gp91-phox. Moreover, some effects of ASP were partially abrogated in the presence of Wortmannin. Discussion: Ox-LDL induced senescence of EPCs via inhibition of telomerase activity, which was influenced by oxidative stress and the Akt/hTERT pathway. The inhibition of EPC senescence by ASP could be important for potential therapeutics. Conclusion: Treatment of EPCs with ASP remarkably attenuates the harmful effects of ox-LDL via augmentation of Akt/hTERT phosphorylation and inhibition of oxidative stress.

Polysaccharide from Angelica sinensis protects H9c2 cells against oxidative injury and endoplasmic reticulum stress by activating the ATF6 pathway

“… 29 Additionally, ASP treatment reduced the senescence of endothelial progenitor cells by relieving OS. 31 However, the effect of ASP on oxidative injury in cardiomyocytes and mechanisms underlying this effect are unclear. H9c2 is a clonal cell line derived from BD1X rat ventricle and exhibits many of the properties of cardiac muscle, such as electrophysiology, ion channels, and receptors.…”

Chinese Angelica Polysaccharide (CAP) Alleviates LPS-Induced Inflammation and Apoptosis by Down-Regulating COX-1 in PC12 Cells

“…It possess a superior clinical efficacy and fewer side effects [14]. For example, angelica sinensis polysaccharides inhibit endothelial progenitor cell senescence through the reduction of oxidative stress and activation of the AKT/hTERT pathway [27]. And it also suppresses cell growth and cell metastasis in human lung adenocarcinoma A549 cells by regulating MMPs/TIMPs and TGF-β1 [23].…”

Visfatin attenuates the ox-LDL-induced senescence of endothelial progenitor cells by upregulating SIRT1 expression through the PI3K/Akt/ERK pathway

“…It has also been demonstrated that ox-LDL also accelerated the senescence of EPCs, leading to cellular dysfunction (13,14). Lai and Liu showed that ox-LDL-induced senescence of EPCs was mediated by oxidative stress and the Akt/hTERT pathway (15).…”