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Abstract：
Introduction: Chronic non-healing wound is a considerable clinical challenge and research into the discovery of novel pro-healing agents is underway as existing therapeutic approaches cannot sufficiently meet current needs. Method: We studied the effects of corylin in cell line fibroblasts and macrophages by Western blots, PCR, Flow cytometry assay, Immunofluorescence. Results: We showed that corylin, a main flavonoid extracted from Psoralea corylifolia L, reduced inflammatory responses, promoted collagen deposition, and accelerated the healing of full-thickness skin wounds in mice. Exploration of the underlying mechanisms showed that corylin activated the PI3K/AKT signaling, leading to fibroblasts\' migration, proliferation, and scratch healing. Corylin also activated sirtuin 1 (SIRT1) signaling, enhanced the deacetylation and cytoplasmic translocation of NF-κB p65, and therefore reduced lipopolysaccharide (LPS)-induced inflammatory responses in macrophages. Furthermore, inhibition of PI3K/AKT and sirtuin 1 pathway with LY294002 and EX527 prevent the therapeutic potency of corylin against chronic wounds. Conclusion: In summary, our results suggested that corylin may be a candidate for the development of novel pro-healing agents.
摘要：
简介：慢性不愈合伤口是一个相当大的临床挑战和研究发现新的促愈合剂正在进行中，因为现有的治疗方法不能充分满足当前的需求。方法：我们通过Western印迹研究了Corylin在细胞系成纤维细胞和巨噬细胞中的作用，PCR,流式细胞术测定，免疫荧光。结果：我们发现corylin，从补骨脂中提取的主要类黄酮，减少炎症反应，促进胶原蛋白沉积，加速小鼠全层皮肤伤口的愈合。对潜在机制的探索表明，corylin激活了PI3K/AKT信号，导致成纤维细胞迁移，扩散,和划痕愈合。Corylin还激活沉默酶1（SIRT1）信号，增强NF-κBp65的脱乙酰和细胞质易位，因此减少了脂多糖（LPS）诱导的巨噬细胞炎症反应。此外，用LY294002和EX527抑制PI3K/AKT和sirtuin1途径可防止Corylin对慢性伤口的治疗效力。结论：总之，我们的结果表明，corylin可能是开发新的促愈合剂的候选药物。
