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).
Highlights
Ischemia after artery obstruction that occurs during peripheral artery disease (PAD) is estimated to affect approximately 202 million adults worldwide (Gerhard-Herman et al, 2017; McDermott and Kibbe, 2017)
Mice undergoing hindlimb ischemia (HLI) showed a time-dependent increase in tissue perfusion that reached about 30% restoration of blood flow by day
Oroxylin A (OA) treatment significantly accelerated perfusion recovery as compared with saline (0.71 ± 0.16 versus 0.45 ± 0.10), similar with the effect of Sim (0.63 ± 0.13), which showed that OA improved hindlimb ischemia in limb ischemic mice (Figures 1A,B)
Summary
Ischemia after artery obstruction that occurs during PAD is estimated to affect approximately 202 million adults worldwide (Gerhard-Herman et al, 2017; McDermott and Kibbe, 2017). The enhancement of angiogenesis and the resulting improvement of blood flow to the limb are the key restorative mechanisms in response to ischemia (Cooke and Losordo, 2015; Suzuki et al, 2016; Albrecht-Schgoer et al, 2017; Fan et al, 2018). At this point, treatments have not been fully effective. Oroxylin A Promotes Angiogenesis at improving blood flow through angiogenesis in PAD (Suzuki et al, 2016; Gorenoi et al, 2017). Previous research has shown that promoting angiogenesis while reducing inflammation can improve the prognosis of PAD (Zhang et al, 2016; Liu et al, 2018)
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