Nano-formulated curcumin accelerates acute wound healing through Dkk-1-mediated fibroblast mobilization and MCP-1-mediated anti-inflammation
Nano-formulated curcumin accelerates acute wound healing through Dkk-1-mediated fibroblast mobilization and MCP-1-mediated anti-inflammation
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DOI：
10.1038/am.2017.31
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发表时间：
2017-03-01
影响因子：
9.7
通讯作者：
Schilling, Arndt F.
中科院分区：
文献类型：
--
作者：
Dai, Xinyi;Liu, Juan;Schilling, Arndt F.
姜黄是姜黄的一种产品，在许多亚洲国家用于治疗伤口的历史非常悠久。姜黄素是姜黄的主要类姜黄素，最近被确定为姜黄药用特性的主要介质。然而，化合物本身的固有局限性，如疏水性、不稳定性、吸收差和快速全身消除，为转化为更广泛的临床应用带来了巨大的障碍。我们在这里提出了一种方法，工程姜黄素/明胶共混纳米纤维垫（NM）通过静电纺丝，以充分提高生物利用度的疏水性姜黄素的伤口修复。姜黄素被成功地配制成无定形纳米固体分散体，并有利地从明胶基仿生纳米材料中释放，其可以容易地局部应用于实验伤口。我们显示了在愈合过程中释放的姜黄素的协同信号传导：（i）通过激活Wnt信号传导途径动员伤口部位成纤维细胞，部分通过Dickkopf相关蛋白-1介导，和（ii）通过降低成纤维细胞单核细胞趋化蛋白-1的表达持续抑制炎症反应。结合这些作用，姜黄素/明胶混合的NM增强了急性伤口大鼠模型的再生过程，为将这种古老的药物用于现代伤口治疗提供了一种方法。
Turmeric, a product of Curcuma longa, has a very long history of being used for the treatment of wounds in many Asian countries. Curcumin, the principal curcuminoid of turmeric, has recently been identified as a main mediator of turmeric's medicinal properties. However, the inherent limitations of the compound itself, such as hydrophobicity, instability, poor absorption and rapid systemic elimination, pose big hurdles for translation to wider clinical application. We present here an approach for engineering curcumin/gelatin-blended nanofibrous mats (NMs) by electrospinning to adequately enhance the bioavailability of the hydrophobic curcumin for wound repair. Curcumin was successfully formulated as an amorphous nanosolid dispersion and favorably released from gelatin-based biomimetic NMs that could be easily applied topically to experimental wounds. We show synergistic signaling by the released curcumin during the healing process: (i) mobilization of wound site fibroblasts by activating the Wnt signaling pathway, partly mediated through Dickkopf-related protein-1, and (ii) persistent inhibition of the inflammatory response through decreased expression of monocyte chemoattractant protein-1 by fibroblasts. With a combination of these effects, the curcumin/gelatin-blended NMs enhanced the regenerative process in a rat model of acute wounds, providing a method for translating this ancient medicine for use in modern wound therapy.