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姜黄素的局部应用调节糖尿病损伤皮肤伤口的血管生成。

Topical application of curcumin regulates the angiogenesis in diabetic-impaired cutaneous wound.

机构信息

Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Department of Molecular Medicine and Genetics, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.

出版信息

Cell Biochem Funct. 2020 Jul;38(5):558-566. doi: 10.1002/cbf.3500. Epub 2020 Feb 6.

DOI:10.1002/cbf.3500
PMID:32030812
Abstract

Diabetic wound characterizes with a delayed repair as a result of the lack of neoangiogenesis and the excess of inflammation. Natural products such as curcumin have shown great promises in their regulatory potentials on inflammation and angiogenesis. However, natural agents have several shortages in their bioavailability and stability when used in vivo. In this study, we have evaluated the efficacy of a topical formulation of curcumin in the enhancement of diabetic wound repair. Streptozocin-induced diabetic mice were wounded, and cream of curcumin (1%) was applied topically to wounds twice daily for different treatment periods. Inflammation, neoangiogenesis, and re-epithelialization were evaluated in each experimental group. Wounds of animals treated with curcumin showed an enhanced neoangiogenesis. Application of topical curcumin also increased the expression level of RelA as the main subunit of the nuclear factor-κB (NF-κB) signalling pathway. However, no significant effects on macrophage polarization and re-epithelialization were observed in the curcumin-treated animals. Our study using a higher concentration of curcumin in the form of a topical cream further confirmed the efficacy of curcumin as an angiogenesis-promoting agent; however, it also conveyed uncertainty over the claimed regulatory effects of curcumin on inflammation. SIGNIFICANCE OF THE STUDY: Diabetes results in several complications such as impaired cutaneous wound repair. Excess of inflammation and lack of angiogenesis are among the main causes of delayed healing in diabetes. Curcumin is famous for its anti-inflammatory properties. However, when in the body curcumin has shown to have a limited benefit unless in high-dosage consumes. This is because of its poor absorption from digestive system and its bioavailability. In this study, we have used a topical formulation of curcumin at a relatively high concentration to enhance the healing of a diabetic wound in an animal model of diabetes. We also have studied different cellular and molecular mechanisms by which curcumin may help the wound repair. Our results re-emphasize the proangiogenic potential of curcumin in diabetic wound environment.

摘要

糖尿病创面的特点是新生血管形成减少和炎症过度,导致修复延迟。姜黄素等天然产物在调节炎症和血管生成方面显示出巨大的潜力。然而,天然药物在体内应用时存在生物利用度和稳定性等方面的不足。在这项研究中,我们评估了姜黄素局部制剂在增强糖尿病创面修复中的疗效。链脲佐菌素诱导的糖尿病小鼠造模后,每天两次将姜黄素乳膏(1%)局部应用于创面,进行不同时间的治疗。在每个实验组中评估炎症、新生血管形成和再上皮化。用姜黄素处理的动物创面表现出增强的新生血管形成。局部应用姜黄素还增加了核因子-κB(NF-κB)信号通路的主要亚基 RelA 的表达水平。然而,在姜黄素处理的动物中,对巨噬细胞极化和再上皮化没有观察到显著影响。我们使用高浓度姜黄素制成的局部乳膏进行的研究进一步证实了姜黄素作为促血管生成剂的疗效;然而,它也对姜黄素对炎症的调节作用的宣称效果提出了质疑。研究意义:糖尿病会导致多种并发症,如皮肤伤口愈合受损。炎症过度和血管生成不足是糖尿病愈合延迟的主要原因之一。姜黄素以其抗炎特性而闻名。然而,在体内,姜黄素的益处有限,除非以高剂量摄入,这是因为它从消化系统中的吸收有限和生物利用度低。在这项研究中,我们使用了相对较高浓度的姜黄素局部制剂来增强糖尿病动物模型中糖尿病创面的愈合。我们还研究了姜黄素可能有助于伤口修复的不同细胞和分子机制。我们的结果再次强调了姜黄素在糖尿病创面环境中的促血管生成潜力。

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