Wound therapy remains a clinical challenge due to the poor vascularization during the healing process and the high demand to achieve functional and aesthetically satisfactory scars. Newly-formed blood vessels are necessary for wound healing since they can deliver nutrients and oxygen to the wound area. In this study, the role of leonurine (LN), a traditional Chinese medicine isolated from Herba leonuri, in promoting angiogenesis and its function in wound healing have been investigated. The results of co-culture with human umbilical vein endothelial cells (HUVECs) demonstrated that LN treatment (5–20 μM) could promote the proliferation and migration and enhance the ability of in vitro angiogenesis through up-regulating the mTOR/ERK signaling pathway. Furthermore, a full-thickness cutaneous wound model was used to investigate the healing effect of LN in vivo. Intragastric administration of 20 mg per kg per day LN stimulated the regeneration of more blood vessels at the wound sites, which confirmed the in vitro results of promoting angiogenesis. Due to fast vascularization, the collagen matrix deposition and remodeling processes were also accelerated in LN treated wounds, resulting in efficient wound healing. In summary, LN promoted angiogenesis of endothelial cells in vitro by activating the mTOR/ERK pathway, and could efficiently enhance the angiogenesis and collagen deposition of the regenerated tissue, together with facilitating the wound healing process in vivo. This study provides evidence for LN-stimulated angiogenesis and tissue regeneration in skin wounds, especially in ischemic wounds.

中文翻译：

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leururine上调mTOR / ERK信号传导在全层皮肤伤口模型中促进血管生成和组织再生

由于在愈合过程中血管形成不良，以及对获得功能性和美学上令人满意的疤痕的需求很高，因此伤口治疗仍然是一项临床挑战。新形成的血管对于伤口愈合是必不可少的，因为它们可以将营养和氧气输送到伤口区域。在这项研究中，研究了Leonurine（LN），从Leonus leonuri分离的中药，在促进血管生成及其在伤口愈合中的作用。与人脐静脉内皮细胞（HUVEC）共培养的结果表明，LN处理（5–20μM）可以促进增殖和迁移并增强体外能力通过上调mTOR / ERK信号通路实现血管生成。此外，使用全厚度皮肤伤口模型来研究LN在体内的愈合效果。腹腔内每天每公斤20 mg LN刺激伤口处更多血管的再生，这证实了促进血管生成的体外结果。由于快速的血管形成，胶原蛋白基质的沉积和重塑过程在LN处理的伤口中也得到了加速，从而实现了有效的伤口愈合。综上所述，LN在体外促进内皮细胞的血管生成通过激活mTOR / ERK途径，可以有效增强再生组织的血管生成和胶原蛋白沉积，并促进体内伤口愈合过程。该研究提供了LN刺激的皮肤伤口，特别是缺血性伤口中的血管生成和组织再生的证据。