Icariin inhibits oxidized low-density lipoprotein-induced proliferation of vascular smooth muscle cells by suppressing activation of extracellular signal-regulated kinase 1/2 and expression of proliferating cell nuclear antigen

Abstract

Icariin, a flavonoid isolated from the traditional Chinese herbal medicine Epimedium brevicornum Maxim, has been shown to possess anti-inflammatory, anti‑oxidant and anti-atherosclerotic activities in vivo and in vitro. The aim of the present study was to investigate the effects of icariin on oxidized low‑density lipoprotein (ox-LDL)-induced proliferation of vascular smooth muscle cells (VSMCs) and the possible underlying mechanism. VSMCs were cultured and pre‑treated with various concentrations of icariin (0, 10, 20 or 40 µm) prior to stimulation by ox‑LDL (50 µg/ml). Cell proliferation was evaluated by an MTT assay. Flow cytometry was used to study the influence of icariin on the cell cycle. Proliferating cell nuclear antigen (PCNA) expression and phosphorylation levels of extracellular signal-regulated kinase (ERK)1/2 were detected by western blot analysis. The results indicated that icariin significantly inhibited ox‑LDL‑induced proliferation of VSMCs and phosphorylation of ERK1/2. Furthermore, icariin also blocked the ox‑LDL‑induced cell‑cycle progression at G1/S‑interphase and downregulated the expression of PCNA in VSMCs. In conclusion, the present study indicated for the first time that icariin reduced the amount of ox‑LDL‑induced proliferation of VSMCs through suppression of PCNA expression and inactivation of ERK1/2.

Icariin affects cell cycle progression and proliferation of human retinal pigment epithelial cells via enhancing expression of H19

“…A prior study found that ICA treatment evidently ameliorated angiotensin II (AngII)-induced cell proliferation in human brain vascular SMCs (HB-VSMCs) (Dong et al, 2019). Meanwhile, our colleagues demonstrated that oxidized low density lipoprotein (ox-LDL) significantly increases cell viability of HA-VSMCs, yet ICA suppressed ox-LDL-induced HA-VSMC proliferation in a concentration-dependent manner (Hu et al, 2016). Previous studies have clearly demonstrated that ox-LDL can promote cell proliferation via activating PDGF receptor-β (PDGFR-β) pathway (Vindis et al, 2006).…”

“…Recently, emerging studies have reported ICA regulates cell cycle progression and proliferation in various cell types. ICA exerted suppressive effects on medulloblastoma cells (Sun et al, 2016b), osteosarcoma cells (Ren, Zhu & Liu, 2018) and human aortic smooth muscle cells (HA-VSMCs) (Hu et al, 2016). Further, the induction of G0/G1 phase arrest was observed in cardiomyocyte and breast cancer cells after treatment with ICA (Zhu et al, 2005;Cheng et al, 2019).…”

The Anticancer Properties of Herba Epimedii and Its Main Bioactive Componentsicariin and Icariside II

“…Icariin has been shown to significantly prohibit the proliferation of vascular smooth muscle cells (VSMCs) and the activation of ERK1/2. Moreover, icariin also induced G1/S phase cell cycle arrest and decreased the expression of PCNA in VSMCs [ 89 ]. Based on these results, it was proposed that the inhibitory effect of icariin on the proliferation of VSMCs might be responsible for the suppression of tumor metastasis.…”

Icariin-loaded electrospun PCL/gelatin sub-microfiber mat for preventing epidural adhesions after laminectomy

“…5,6 Moreover, the anti-angiogenic activity of ICA was confirmed by the inhibition of the proliferation of vascular smooth muscle cells through inactivation of the ERK1/2 signaling pathway. 7 However, we are not aware of any studies focused on the anti-adhesion roles and mechanisms of ICA in blocking epidural adhesion formation.…”