Isookanin Inhibits PGE2-Mediated Angiogenesis by Inducing Cell Arrest through Inhibiting the Phosphorylation of ERK1/2 and CREB in HMEC-1 Cells

Abstract

Inflammation is increasingly recognized as a critical mediator of angiogenesis, and unregulated angiogenic responses often involve human diseases. The importance of regulating angiogenesis in inflammatory diseases has been demonstrated through some successful cases of anti-angiogenesis therapies in related diseases, including arthritis, but it has been reported that some synthetic types of antiangiogenic drugs have potential side effects. In recent years, the importance of finding alternative strategies for regulating angiogenesis has begun to attract the attention of researchers. Therefore, identification of natural ingredients used to prevent or treat angiogenesis-related diseases will play a greater role. Isookanin is a phenolic flavonoid presented in Bidens extract, and it has been reported that isookanin possesses some biological properties, including antioxidative and anti-inflammatory effects, anti-diabetic properties, and an ability to inhibit α-amylase. However, its antiangiogenic effects and mechanism thereof have not been studied yet. In this study, our results indicate that isookanin has an effective inhibitory effect on the angiogenic properties of microvascular endothelial cells. Isookanin shows inhibitory effects in multiple stages of PGE2-induced angiogenesis, including the growth, proliferation, migration, and tube formation of microvascular endothelial cells. In addition, isookanin induces cell cycle arrest in S phase, which is also the reason for subsequent inhibition of cell proliferation. The mechanism of inhibiting angiogenesis by isookanin is related to the inhibition of PGE2-mediated ERK1/2 and CREB phosphorylation. These findings make isookanin a potential candidate for the treatment of angiogenesis-related diseases.

Pathological angiogenesis: mechanisms and therapeutic strategies

“…Current treatments for arthritis include non-steroidal anti-inflammatory drugs. Interestingly, the use of these drugs may indirectly inhibit angiogenesis by suppression of prostaglandin E2 production or by inhibition of MMPs [ 182 , 183 ]. More specific treatment involves immunomodulating monoclonal antibodies against TNFα and IL-6 [ 184 , 185 ], an approach that also indirectly lowers the VEGF content in serum and synovium, leading to a reduction of angiogenesis in the synovial tissue.…”

Immunomodulatory effects and associated mechanisms ofMomordica charantiaand its phytochemicals

“…37 Therefore, inhibition of PGE2 production shows great potential for ameliorating inflammatory symptoms and suppressing related diseases. 93 PPARs are transcription factors belonging to the nuclear hormone receptor superfamily. 94 PPAR activators can inhibit the activation of inflammatory response genes, such as IL-2, IL-6, IL-8, TNF-α and metalloproteases, by negatively interfering with the NF-κB, STAT3 and AP-1 signalling pathways.…”

Down-regulation of β-lactam antibiotics resistance and biofilm formation by Staphylococcus epidermidis is associated with isookanin

“…Flavonoids are a class of compounds with anti-biofilm activity, such as rutin, quercetin, and baicalin, etc ( Mu et al., 2020 ; Ivanov et al., 2022 ; Han et al., 2023 ). Isookanin is also a class of flavonoids isolated and extracted from Compositae , which has antioxidant and anti-inflammatory effects, anti-diabetic properties, and other activities such as inhibition of α-amylase and anti-angiogenesis ( Xin et al., 2021 ). Moreover, it has a good effect on cardiovascular diseases ( Wang et al., 2015 ).…”

“…Moreover, it has a good effect on cardiovascular diseases ( Wang et al., 2015 ). Isookanin also could increased the relative abundance of Bifidobacterium and Lactobacillus and could reduce the primary metabolism functions of the microbiota in vitro ( Xin et al., 2021 ). Isookanin has various activities, However, its inhibiting bacterial biofilms have not been reported yet.…”