Institute of Life Sciences, Engineering Laboratory of Zhejiang Province for Pharmaceutical Development of Growth Factors, Biomedical Collaborative Innovation Center of Wenzhou, Wenzhou University, Zhejiang, China.
Department of Orthopedics Surgery, Lishui People's Hospital, The Sixth Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang, China.
Arch Biochem Biophys. 2023 Nov;749:109790. doi: 10.1016/j.abb.2023.109790. Epub 2023 Oct 17.
Skin wound healing is a dynamic and complex process that involves multiple physiological and cellular events. Grape seed proanthocyanidins (GSP) have strong anti-oxidation and elimination of oxygen free radicals, and have been shown to significantly promote wound healing, but the underlying mechanism remains unclear. Studies have indicated that reactive oxygen species (ROS) acts as an upstream signal to induce mitophagy, suggesting that GSP can regulate mitophagy through the signal pathway. This study aimed to investigate whether GSP regulates mitophagy by down-regulating oxidative stress to promote wound healing. In vivo, GSP treatment accelerated wound healing, granulation tissue formation, collagen deposition, and angiogenesis in mice. Moreover, GSP down-regulated ROS levels and promoted the expression of antioxidant proteins by up-regulating the expression of p-JNK/FOXO3a protein, thereby regulating the expression of mitophagy-related proteins. In vitro, 4 μg/mL GSP showed no apparent toxic effects on cells and effectively reduce the oxidative stress damage of cells induced by HO. Western blot and superoxide anion fluorescence probe further confirmed that GSP effectively reduced Dihydroethidium content and up-regulated the expression of antioxidant proteins by activation of p-JNK/FOXO3a protein expression, thereby regulating mitophagy. Taken together, the findings from in vitro and in vivo experiments provide new insights into the promotion of wound healing by GSP.
皮肤伤口愈合是一个动态而复杂的过程，涉及多个生理和细胞事件。葡萄籽原花青素（GSP）具有很强的抗氧化和清除自由基的作用，已被证明能显著促进伤口愈合，但具体的作用机制尚不清楚。有研究表明，活性氧（ROS）作为上游信号诱导自噬，提示 GSP 可以通过信号通路调节自噬。本研究旨在探讨 GSP 是否通过下调氧化应激来调节自噬，从而促进伤口愈合。在体内，GSP 处理可加速小鼠伤口愈合、肉芽组织形成、胶原沉积和血管生成。此外，GSP 通过上调 p-JNK/FOXO3a 蛋白表达，降低 ROS 水平并促进抗氧化蛋白的表达，从而调节自噬相关蛋白的表达。在体外，4μg/mL 的 GSP 对细胞无明显毒性作用，并能有效减轻 HO 诱导的细胞氧化应激损伤。Western blot 和超氧阴离子荧光探针进一步证实，GSP 通过激活 p-JNK/FOXO3a 蛋白表达，有效降低 Dihydroethidium 含量并上调抗氧化蛋白的表达，从而调节自噬。总之，体内外实验结果为 GSP 促进伤口愈合提供了新的见解。
