PMID- 34413777 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210821 IS - 1663-9812 (Print) IS - 1663-9812 (Electronic) IS - 1663-9812 (Linking) VI - 12 DP - 2021 TI - Oroxylin a Attenuates Limb Ischemia by Promoting Angiogenesis via Modulation of Endothelial Cell Migration. PG - 705617 LID - 10.3389/fphar.2021.705617 [doi] LID - 705617 AB - 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-1beta, 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). CI - Copyright (c) 2021 Zhang, Chen, Li, Shi, Wang, Yang, Fang, Leng, Sun, Li, Xue, Gao and Wang. FAU - Zhang, Lusha AU - Zhang L AD - State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China. AD - Key Laboratory of Pharmacology of Traditional Chinese Medical Formula, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China. FAU - Chen, Lu AU - Chen L AD - State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China. AD - Key Laboratory of Pharmacology of Traditional Chinese Medical Formula, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China. AD - Tianjin Key Laboratory of Traditional Chinese Medicine Pharmacology, Tianjin, China. AD - Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin, China. AD - Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China. FAU - Li, Chunxiao AU - Li C AD - State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China. AD - Key Laboratory of Pharmacology of Traditional Chinese Medical Formula, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China. AD - Tianjin Key Laboratory of Traditional Chinese Medicine Pharmacology, Tianjin, China. FAU - Shi, Hong AU - Shi H AD - State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China. AD - Key Laboratory of Pharmacology of Traditional Chinese Medical Formula, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China. AD - Tianjin Key Laboratory of Traditional Chinese Medicine Pharmacology, Tianjin, China. AD - Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin, China. AD - Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China. FAU - Wang, Qianyi AU - Wang Q AD - State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China. AD - Key Laboratory of Pharmacology of Traditional Chinese Medical Formula, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China. FAU - Yang, Wenjie AU - Yang W AD - State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China. AD - Key Laboratory of Pharmacology of Traditional Chinese Medical Formula, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China. FAU - Fang, Leyu AU - Fang L AD - State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China. AD - Key Laboratory of Pharmacology of Traditional Chinese Medical Formula, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China. FAU - Leng, Yuze AU - Leng Y AD - State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China. AD - Key Laboratory of Pharmacology of Traditional Chinese Medical Formula, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China. FAU - Sun, Wei AU - Sun W AD - State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China. AD - Key Laboratory of Pharmacology of Traditional Chinese Medical Formula, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China. FAU - Li, Mengyao AU - Li M AD - State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China. AD - Key Laboratory of Pharmacology of Traditional Chinese Medical Formula, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China. FAU - Xue, Yuejin AU - Xue Y AD - State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China. AD - Key Laboratory of Pharmacology of Traditional Chinese Medical Formula, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China. FAU - Gao, Xiumei AU - Gao X AD - State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China. AD - Key Laboratory of Pharmacology of Traditional Chinese Medical Formula, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China. AD - Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin, China. FAU - Wang, Hong AU - Wang H AD - State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China. AD - Key Laboratory of Pharmacology of Traditional Chinese Medical Formula, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China. AD - Tianjin Key Laboratory of Traditional Chinese Medicine Pharmacology, Tianjin, China. AD - Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin, China. AD - School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China. LA - eng PT - Journal Article DEP - 20210730 PL - Switzerland TA - Front Pharmacol JT - Frontiers in pharmacology JID - 101548923 PMC - PMC8370028 OTO - NOTNLM OT - angiogenesis OT - endothelial cells OT - hind limb ischemia OT - inflammation OT - migration OT - oroxylin A COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/08/21 06:00 MHDA- 2021/08/21 06:01 PMCR- 2021/07/30 CRDT- 2021/08/20 07:01 PHST- 2021/05/05 00:00 [received] PHST- 2021/07/16 00:00 [accepted] PHST- 2021/08/20 07:01 [entrez] PHST- 2021/08/21 06:00 [pubmed] PHST- 2021/08/21 06:01 [medline] PHST- 2021/07/30 00:00 [pmc-release] AID - 705617 [pii] AID - 10.3389/fphar.2021.705617 [doi] PST - epublish SO - Front Pharmacol. 2021 Jul 30;12:705617. doi: 10.3389/fphar.2021.705617. eCollection 2021.