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香豆素醇通过 AMPK 介导的抑制炎症和 TGFβ1 信号通路改善高脂饮食喂养小鼠的伤口愈合。

Patchouli alcohol improves wound healing in high fat diet-fed mice through AMPK-mediated suppression of inflammation and TGFb1 signaling.

机构信息

Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Republic of Korea.

Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Republic of Korea; Department of Global Innovative Drugs, Graduate School of Chung-Ang University, Seoul, Republic of Korea.

出版信息

Biochem Biophys Res Commun. 2021 Jul 5;561:136-142. doi: 10.1016/j.bbrc.2021.05.036. Epub 2021 May 20.

Abstract

Obesity impairs wound healing with substantial alterations in skin inflammation. Patchouli alcohol (PA), extracted from patchouli, has been reported to ameliorate inflammation in various cell types. However, the effects of PA on inflammation and wound healing have not been reported to date. In the present study, we examined whether PA affects cutaneous wound healing in high fat diet (HFD)-fed mice and explored PA-mediated molecular mechanisms through in vitro experiments. We found that PA administration accelerated wound healing as well as ameliorates inflammation in skin of HFD-fed mice. PA treatment augmented AMP-activated protein kinase (AMPK) phosphorylation and TGFb1 expression. PA enhanced cell migration and suppressed inflammation in LPS-treated HaCaT cells. Further, PA increased dose-dependently AMPK phosphorylation as along with TGFb1 and cell migration markers expression. siRNA for AMPK or TGFb1 abrogated the effects of PA on cell migration and inflammation. TGFb1 siRNA mitigated PA-induced expression of cell migration markers. These results suggest that PA ameliorates wound healing via AMPK and TGFb1-mediated suppression of inflammation. In sum, PA can be used as a novel treatment strategy for wound healing in obesity or insulin resistance.

摘要

肥胖症通过对皮肤炎症的实质性改变来损害伤口愈合。已报道从广藿香中提取的广藿香醇(PA)可改善各种细胞类型的炎症。然而,迄今为止,尚未有报道称 PA 对炎症和伤口愈合有影响。在本研究中,我们研究了 PA 是否会影响高脂肪饮食(HFD)喂养的小鼠的皮肤伤口愈合,并通过体外实验探讨了 PA 介导的分子机制。我们发现,PA 给药可加速 HFD 喂养小鼠的伤口愈合,并改善皮肤炎症。PA 处理可增强 AMP 激活的蛋白激酶(AMPK)磷酸化和 TGFb1 的表达。PA 增强了 LPS 处理的 HaCaT 细胞的细胞迁移并抑制了炎症。此外,PA 可剂量依赖性地增加 AMPK 磷酸化以及 TGFb1 和细胞迁移标志物的表达。用 AMPK 或 TGFb1 的 siRNA 消除了 PA 对细胞迁移和炎症的影响。TGFb1 siRNA 减轻了 PA 诱导的细胞迁移标志物的表达。这些结果表明,PA 通过 AMPK 和 TGFb1 介导的炎症抑制来改善伤口愈合。总之,PA 可作为肥胖或胰岛素抵抗患者伤口愈合的新型治疗策略。

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