Oroxylin a Attenuates Limb Ischemia by Promoting Angiogenesis via Modulation of Endothelial Cell Migration

Abstract

Oroxylin A (OA) has been shown to simultaneously increase coronary flow and provide a strong anti-inflammatory effect. In this study, we described the angiogenic properties of OA. OA treatment accelerated perfusion recovery, reduced tissue injury, and promoted angiogenesis after hindlimb ischemia (HLI). In addition, OA regulated the secretion of multiple cytokines, including vascular endothelial growth factor A (VEGFA), angiopoietin-2 (ANG-2), fibroblast growth factor-basic (FGF-2), and platelet derived growth factor BB (PDGF-BB). Specifically, those multiple cytokines were involved in cell migration, cell population proliferation, and angiogenesis. These effects were observed at 3, 7, and 14 days after HLI. In skeletal muscle cells, OA promoted the release of VEGFA and ANG-2. After OA treatment, the conditioned medium derived from skeletal muscle cells was found to significantly induce endothelial cell (EC) proliferation. OA also induced EC migration by activating the Ras homolog gene family member A (RhoA)/Rho-associated coiled-coil kinase 2 (ROCK-II) signaling pathway and the T-box20 (TBX20)/prokineticin 2 (PROK2) signaling pathway. In addition, OA was able to downregulate the number of macrophages and neutrophils, along with the secretion of interleukin-1β, at 3 days after HLI. These results expanded current knowledge about the beneficial effects of OA in angiogenesis and blood flow recovery. This research could open new directions for the development of novel therapeutic intervention for patients with peripheral artery disease (PAD).

Oroxylin A ameliorates AKI-to-CKD transition through maintaining PPARα-BNIP3 signaling-mediated mitochondrial homeostasis

“…In carcinoma, OA could increase ROS level, induce apoptosis, suppress angiogenesis and enhance mitochondrial dysfunction via inactivating sirtuin 1 (SIRT1)-forkhead box O3 (FOXO3)-BNIP3 axis ( Lu et al, 2016 ; Yao et al, 2021 ). However, in normal tissues, OA plays a protective effect through inhibiting mitochondrial ROS, repressing inflammatory response, and promoting angiogenesis ( Lu et al, 2016 ; Kai et al, 2020 ; Zhang et al, 2021 ). Recently, a literature review compared the inconsistent roles of OA in tumors and normal tissues, and found the high selectivity of OA due to the unfolded protein response and protein kinase B pathway, since OA (100–200 μM) selectively killed many more hepatocellular carcinoma cells (HepG2) than normal hepatocytes (L02) ( Mu et al, 2009 ; Xu et al, 2012 ; Lu et al, 2016 ).…”

Research progress of traditional Chinese medicine in improving hepatic fibrosis based on inhibiting pathological angiogenesis

“…Consequently, it helps to protect liver function and prevent liver tissue damage, thus achieving the goal of preventing and treating hepatic fibrosis ( Zhang et al, 2018 ). Another study investigated the effects of oroxylin A on HSC activation and angiogenesis in vitro ( Zhang L. et al, 2021 ). The researchers found that oroxylin A inhibited the activation of HSCs by reducing their expression of α-SMA and col-I ( Chen et al, 2018 ).…”

Oroxylin A: A Promising Flavonoid for Prevention and Treatment of Chronic Diseases

“…OA has shown beneficial effects in angiogenesis and blood flow recovery by elevating VEGFA, angiopoetin-2 (Ang-2), fibroblast growth factor (FGF-2), platelet-derived growth factor (PDGF-BB) levels and promoting endothelial cell (EC) proliferation and migration. Further, OA has also been shown to downregulate macrophages and neutrophils, thereby opening new possibilities in the treatment of HLI [ 153 ].…”