Icariin Promotes Angiogenic Differentiation and Prevents Oxidative Stress-Induced Autophagy in Endothelial Progenitor Cells

Abstract

Reduced tissue levels of endothelial progenitor cells (EPCs) and functional impairment of endothelium are frequently observed in patients with diabetes and cardiovascular disease. The vascular endothelium is specifically sensitive to oxidative stress, and this is one of the mechanisms that causes widespread endothelial dysfunction in most cardiovascular diseases and disorders. Hence attention has increasingly been paid to enhance mobilization and differentiation of EPCs for therapeutic purposes. The aim of this study was to investigate whether Icariin, a natural bioactive component known from traditional Chinese Medicine, can induce angiogenic differentiation and inhibit oxidative stress-induced cell dysfunction in bone marrow-derived EPCs (BMEPCs), and, if so, through what mechanisms. We observed that treatment of BM-EPCs with Icariin significantly promoted cell migration and capillary tube formation, substantially abrogated hydrogen peroxide (H 2 O 2 )-induced apoptotic and autophagic programmed cell death that was linked to the reduced intracellular reactive oxygen species levels and restored mitochondrial membrane potential. Icariin downregulated endothelial nitric oxide synthase 3, as well as nicotinamide-adenine dinucleotide phosphate-oxidase expression upon H 2 O 2 induction. These antiapoptotic and antiautophagic effects of Icariin are possibly mediated by restoring the loss of mammalian target of rapamycin /p70S6K/4EBP1 phosphorylation as well as attenuation of ATF2 and ERK1/2 protein levels after H 2 O 2 treatment. In summary, favorable modulation of the angiogenesis and redox states in BM-EPCs make Icariin a promising proangiogenic agent both enhancing vasculogenesis and protecting against endothelial dysfunction.

Icariin Protects against Glucocorticoid-Induced Osteonecrosis of the Femoral Head in Rats

“…The important point of oxidative stress modulates osteogenic and adipogenic differentiation has received much attention [47]. Recently, the activity of ICA supplementation in reducing oxidative stress has been reported [48] and confirmed in our previous study [14]. Thus, we speculate that ICA regulates the pathways of BMP2/Runx2 and PPARγ by reducing oxidative stress in GC-induced ONFH.…”

Monotropein promotes angiogenesis and inhibits oxidative stress‐induced autophagy in endothelial progenitor cells to accelerate wound healing

“…It has been reported blood vessels were impaired in diabetes mellitus, atherosclerosis and hypertension, which may be related to the presence of oxidative stress and increased concentration of oxidation products . Oxidative stress‐mediated apoptosis would lead to ROS formation and the loss of MMP through the mitochondrial pathway . Notably, Mtp significantly increased the viability of TBHP‐treated cells by reducing ROS formation.…”

Combination of mesenchymal stem cell injection with icariin for the treatment of diabetes-associated erectile dysfunction

“…Icariin, a major flavonoid isolated from the traditional oriental herbal medicine Epimedium koreanum Nakai [23], received our particular attention in recent years for its broad bioactivities and applications, such as its anti-oxidative capacity, cardio-protective effects, and immunological function regulation [24–27]. Icariin had been applicated in the treatment of ED though the mechanisms were still ambiguous, suggesting the feasibility of applying icariin for the MSCs-based ED therapy [28].…”