Wogonin influences vascular permeability via Wnt/β-catenin pathway

Abstract

Wogonin, a flavone from the root of Scutellaria baicalensis Georgi, has shown various biological activities. In our previous study, it was confirmed that wogonin could decrease the expression of hypoxia-inducible factor-1α (HIF-1α) by affecting its stability under hypoxia. However, it is still unknown whether wogonin could influence Wnt/β-catenin pathway under hypoxia. In this study, we found that wogonin disrupted Wnt/β-catenin signaling and reduced the secretion of vascular endothelial growth factor (VEGF, also known as vascular permeability factor, VPF), which increased vascular permeability in certain diseases. It was found that wogonin suppressed HUVECs hyperactivity and actin remodeling induced by hypoxia, inhibited transendothelial cell migration of the human breast carcinoma cell MDA-MB-231 and the extravasated Evans in vivo Miles vascular permeability assay. Wogonin-treated cells showed a decrease in the expression of Wnt protein and its co-receptors, as well as a parallel increase in the expression of Axin and GSK-3β in degradation complex, leading to degradation of β-catenin. In addition, wogonin promoted the binding between Axin and β-catenin, increased ubiquitination of β-catenin and promoted its degradation. Interestingly, wogonin decreased the expression of TCF-1, TCF-3, and LEF-1 and inhibited nuclear accumulation of β-catenin as well as the binding of β-catenin and TCF-1, TCF-3, or LEF-1. All of the above results showed that wogonin could inhibit the expression of VEGF, which is an important factor regulated by β-catenin. Taken together, the results suggested that wogonin was a potent inhibitor of Wnt/β-catenin and influenced vascular permeability, and this might provide new therapeutics in certain diseases.

Could an endoneurial endothelial crosstalk between Wnt/β-catenin and Sonic Hedgehog pathways underlie the early disruption of the infraorbital blood–nerve barrier following chronic constriction injury?

“…Indeed, previous studies have shown an activation of Wnt/β-catenin pathway under hypoxic conditions and an increase in vascular permeability in response to an hypoxic insult. 31 , 32 Furthermore, a recent study by Lim et al. 33 has underlined the role of endoneurial hypoxia resulting from peripheral nerve injury in the genesis of neuropathic pain.…”

Oroxylin A inhibits invasion and migration through suppressing ERK/GSK‐3β signaling in snail‐expressing non‐small‐cell lung cancer cells

“…We found OA could down‐regulate LiCl‐indcued p‐GSK‐3β as well, which indicated OA could promote the activation of GSK‐3β. Interestingly, wogonin could also inhibit Wnt/β‐catenin in our previous research, which suggests that this type of flavonoids promises to be an inhibitor in Wnt/β‐catenin .…”

Topical Application of Wogonin Provides a Novel Treatment of Knee Osteoarthritis

“…Owing to this data, we believe that the diminished NF-κB activity demonstrated in this and separate (Xu et al, 2017) instances caused by wogonin comes through a modulatory effect on ciliary signaling. In addition to this data, it is known that wogonin has been demonstrated in separate instances to have inhibitory activity on SHH (Owen et al, 2017) and WNT signaling (Song et al, 2015), processes which are upregulated in osteoarthritis (Luyten et al, 2009;Chang et al, 2012) and mediated by the primary cilium. The fact that wogonin directly counters these pathways with strong connections to the primary cilia and possesses antiosteoarthritic activity strongly suggests that wogonin exerts some sort of corrective action on the primary cilia, and future research should focus on interactions between wogonin and ciliary homeostasis.…”