Total Flavones ofAbelmoschus manihotExhibits Pro-Angiogenic Activity by Activating the VEGF-A/VEGFR2-PI3K/Akt Signaling Axis

Abstract

Angiogenesis is a process of new blood vessel formation from pre-existing vessels. Vascular endothelial growth factor-A (VEGF-A) binds to VEGF receptor-2 (VEGFR2) and thus activation of phosphatidylinositol 3-kinase (PI3K)/Akt pathway play a central role in angiogenesis. Total flavones of Abelmoschus manihot (TFA), the major active component of the traditional Chinese herb Abelmoschus manihot, display novel pro-angiogenic activity. However, little information concerning its underlying mechanism is available. Here we investigate the pro-angiogenesis of TFA with the aim of understanding its mechanism of action. Human umbilical vein endothelial cells (HUVECs) and the chick chorioallantoic membrane (CAM) model were used to evaluate pro-angiogenesis of TFA using cell viability, wounding healing, transwell invasion, tube formation, RT-qPCR and Western blot methods. LY294002, a PI3K inhibitor, was used to interfere with PI3K/Akt pathway signal for assessing the underlying mechanism. Results in vitro indicated TFA obviously promoted HUVECs proliferation, migration, invasion and tube formation. Furthermore, TFA markedly augmented PI3K and Akt phosphorylation and up-regulated VEGF-A and VEGFR2 expression in HUVECs. However, pre-treatment with LY294002 not only markedly attenuated TFA-induced cells proliferation, migration, invasion and tube formation, but also significantly abolished TFA-induced VEGF-A and VEGFR2 over-expression as well as PI3K and Akt phosphorylation. Experiments in CAM model showed TFA significantly promoted the formation of branched blood vessels and was dramatically suppressed by LY294002. Taken together, TFA promoted angiogenesis both in vitro and in vivo which, however, were counteracted by LY294002, suggesting at least in part, TFA exhibits pro-angiogenic activity by activating the VEGF-A/VEGFR2-PI3K/Akt signaling axis.

Clusterin suppresses spermatogenic cell apoptosis to alleviate diabetes‐induced testicular damage by inhibiting autophagy via the PI3K/AKT/mTOR axis

“…In the present study, we also demonstrated that the CLU‐induced suppression of spermatogenic cell autophagy and apoptosis and diabetes‐induced testicular damage were mediated by the effects of CLU on the activation of PI3K/AKT/mTOR signalling. LY294002 is a potent inhibitor of the PI3K protein family [Zhu, Tang, Lv et al., 2018] and effectively abrogated the suppression of spermatogenic cell autophagy and apoptosis caused by CLU overexpression in this study. Moreover, LY294002 was shown to markedly exacerbate testicular damage in the diabetic rat model, which established the essential roles of PI3K/AKT/mTOR signalling in CLU‐regulated spermatogenic cell functions and testicular dysfunctions associated with diabetes pathogenesis.…”

Different effects of allergic rhinitis on nasal mucosa remodeling in chronic rhinosinusitis with and without nasal polyps

“…VEGF is a family of homodimeric proteins that consisted by six members, including VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E and placenta growth factor [ 30 ]. VEGF-A, the most studied VEGF family member, was shown to play a pivotal role in neovascularization regulation [ 31 ]. CD34, a cell surface sialomucin, is involved in a variety of pathophysiologic processes, including cell adhesion, inflammatory cell recruitment and angiogenesis.…”

Quercetin Antagonizes Glucose Fluctuation Induced Renal Injury by Inhibiting Aerobic Glycolysis via HIF-1α/miR-210/ISCU/FeS Pathway

“…Quercetin distributes in various fruits and vegetables and is one of bioflavonoid compounds of Abelmoschus plants, which has been reported as a potential therapeutic herb for the treatment of DN in our previous studies (14,15) and other studies (16,17). Quercetin shows diverse pharmacological effects, including anti-oxidation and anti-inflammatory (18,19).…”