Functional and mechanistic investigation of Shikonin in scarring
Functional and mechanistic investigation of Shikonin in scarring
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紫草素在疤痕形成中的功能和机制研究
DOI：
10.1016/j.cbi.2014.12.037
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发表时间：
2015-02-25
影响因子：
5.1
通讯作者：
Upton, Zee
中科院分区：
文献类型：
--
作者：
Xie, Yan;Fan, Chen;Upton, Zee
疤痕是一个重大的医疗负担;财政上的医疗保健系统和身体和心理上的病人。重要的是，有许多病例报告描述了烧伤疤痕中癌症的发生。目前可用的疗法由于其不期望的副作用、复杂的递送途径、长期使用的要求和/或费用而不令人满意。紫草是一种多年生草本植物，在亚洲临床上用于治疗烧伤和瘢痕已有数千年的历史。紫草素是从紫草中提取的一种有效成分，具有诱导肿瘤细胞凋亡的作用。细胞凋亡是瘢痕组织重塑的重要过程。因此推测紫草素可能诱导瘢痕相关细胞凋亡。本研究首次在体外详细研究了瘢痕相关细胞对紫草素的功能反应，并探讨了这些反应的机制。所获得的数据表明，紫草素抑制细胞活力和增殖，并减少可检测到的胶原在瘢痕来源的成纤维细胞。进一步的研究表明紫草素通过差异调节caspase 3、Bcl-2、磷酸化Erk 1/2和磷酸化p38的表达诱导瘢痕成纤维细胞凋亡。此外，紫草素下调胶原蛋白I、胶原蛋白III和α-平滑肌肌动蛋白基因的表达，从而减弱瘢痕源性成纤维细胞中的胶原蛋白合成。总之，它表明紫草素诱导细胞凋亡，减少胶原蛋白的产生在瘢痕相关的成纤维细胞，因此可能持有作为一种新的瘢痕修复疗法的潜力。(C)2015爱思唯尔爱尔兰有限公司版权所有。
Scarring is a significant medical burden; financially to the health care system and physically and psychologically for patients. Importantly, there have been numerous case reports describing the occurrence of cancer in burn scars. Currently available therapies are not satisfactory due to their undesirable side-effects, complex delivery routes, requirements for long-term use and/or expense. Radix Amebiae (Zi Cao), a perennial herb, has been clinically applied to treat burns and manage scars for thousands of years in Asia. Shikonin, an active component extracted from Radix Arnebiae, has been demonstrated to induce apoptosis in cancer cells. Apoptosis is an essential process during scar tissue remodelling. It was therefore hypothesized that Shikonin may induce apoptosis in scar-associated cells. This investigation presents the first detailed in vitro study examining the functional responses of scar-associated cells to Shikonin, and investigates the mechanisms underlying these responses. The data obtained suggests that Shikonin inhibits cell viability and proliferation and reduces detectable collagen in scar-derived fibroblasts. Further investigation revealed that Shikonin induces apoptosis in scar fibroblasts by differentially regulating the expression of caspase 3, Bcl-2, phospho-Erk1/2 and phospho-p38. In addition, Shikonin down-regulates the expression of collagen I, collagen III and alpha-smooth muscle actin genes hence attenuating collagen synthesis in scar-derived fibroblasts. In summary, it is demonstrated that Shikonin induces apoptosis and decreases collagen production in scar-associated fibroblasts and may therefore hold potential as a novel scar remediation therapy. (C) 2015 Elsevier Ireland Ltd. All rights reserved.