Department of Burns and Plastic Surgery, Kunshan Hospital Affiliated to Jiangsu University, Kunshan 215300, Jiangsu, China.
Department of Rehabilitation Medicine, Kunshan Hospital Affiliated to Jiangsu University, Kunshan 215300, Jiangsu, China.
Aging (Albany NY). 2024 Jan 26;16(3):2398-2409. doi: 10.18632/aging.205487.
Keloids pose a significant dermatological challenge, marked by abnormal fibroblast proliferation and excessive collagen deposition in response to skin injury or trauma. In the present study, we introduce DMC-HA, a derivative of Curcumin, as a promising candidate for keloid treatment. DMC-HA is poised to provide superior therapeutic benefits compared to Curcumin due to its structural modifications. Examining the comparative effects of DMC-HA and Curcumin on keloid fibroblasts can offer insights into their potential as therapeutic agents and the underlying mechanisms in keloid pathogenesis. In our study, CCK-8 experiments revealed that, at equivalent concentrations, DMC-HA demonstrated greater efficacy in inhibiting the proliferation of keloid fibroblasts compared to Curcumin. Flow cytometry analysis indicated that DMC-HA induced fibroblast apoptosis more significantly than Curcumin at the same concentration. Further data demonstrated that DMC-HA notably increased the production of reactive oxygen species (ROS), upregulated the expression levels of Bax, cleaved PARP, and cleaved Caspase-3. Interestingly, the impact of DMC-HA was reversed upon the application of the antioxidant NAC. Additionally, DMC-HA could suppress IL-6-induced increased expression of p-STAT3. Collectively, our findings suggest that DMC-HA is more effective than Curcumin in inhibiting the proliferation of keloid fibroblasts. The underlying mechanism of its action appears to be associated with the augmentation of ROS induction and the concurrent inhibition of STAT3 activation.
瘢痕疙瘩是一种显著的皮肤挑战,其特征是在皮肤损伤或创伤后,异常的成纤维细胞增殖和过多的胶原蛋白沉积。在本研究中,我们引入姜黄素衍生物 DMC-HA,作为瘢痕疙瘩治疗的有前途的候选药物。由于结构修饰,DMC-HA 有望提供优于姜黄素的治疗益处。研究 DMC-HA 和姜黄素对瘢痕疙瘩成纤维细胞的比较作用,可以深入了解它们作为治疗剂的潜力以及瘢痕疙瘩发病机制中的潜在机制。在我们的研究中,CCK-8 实验表明,在等效浓度下,DMC-HA 比姜黄素更有效地抑制瘢痕疙瘩成纤维细胞的增殖。流式细胞术分析表明,在相同浓度下,DMC-HA 诱导成纤维细胞凋亡的效果比姜黄素更为显著。进一步的数据表明,DMC-HA 显著增加了活性氧物种(ROS)的产生,上调了 Bax 的表达水平,PARP 切割,Caspase-3 切割。有趣的是,抗氧化剂 NAC 的应用逆转了 DMC-HA 的作用。此外,DMC-HA 可以抑制 IL-6 诱导的 p-STAT3 表达增加。总之,我们的研究结果表明,DMC-HA 比姜黄素更有效地抑制瘢痕疙瘩成纤维细胞的增殖。其作用机制似乎与 ROS 诱导的增强和 STAT3 激活的同时抑制有关。