Department of Dermatology & Cutaneous Biology, Research Institute, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
Scar Laser and Plastic Surgery Center, Yonsei Cancer Hospital, Seoul 03722, Republic of Korea.
Int J Mol Sci. 2023 Sep 21;24(18):14386. doi: 10.3390/ijms241814386.
Keloid scars are fibro-proliferative conditions characterized by abnormal fibroblast proliferation and excessive extracellular matrix deposition. The mammalian target of the rapamycin (mTOR) pathway has emerged as a potential therapeutic target in keloid disease. Silibinin, a natural flavonoid isolated from the seeds and fruits of the milk thistle, is known to inhibit the mTOR signaling pathway in human cervical and hepatoma cancer cells. However, the mechanisms underlying this inhibitory effect are not fully understood. This in vitro study investigated the effects of silibinin on collagen expression in normal human dermal and keloid-derived fibroblasts. We evaluated the effects of silibinin on the expressions of collagen types I and III and assessed its effects on the suppression of the mTOR signaling pathway. Our findings confirmed elevated mTOR phosphorylation levels in keloid scars compared to normal tissue specimens. Silibinin treatment significantly reduced collagen I and III expressions in normal human dermal and keloid-derived fibroblasts. These effects were accompanied by the suppression of the mTOR signaling pathway. Our findings suggest the potential of silibinin as a promising therapeutic agent for preventing and treating keloid scars. Further studies are warranted to explore the clinical application of silibinin in scar management.
瘢痕疙瘩是一种纤维增生性疾病,其特征是成纤维细胞异常增殖和细胞外基质过度沉积。哺乳动物雷帕霉素靶蛋白(mTOR)途径已成为瘢痕疙瘩疾病的潜在治疗靶点。水飞蓟素是从奶蓟的种子和果实中分离出来的一种天然类黄酮,已知它可以抑制人宫颈和肝癌细胞中的 mTOR 信号通路。然而,这种抑制作用的机制尚不完全清楚。这项体外研究调查了水飞蓟素对正常人类真皮和成纤维细胞来源的瘢痕疙瘩中胶原表达的影响。我们评估了水飞蓟素对胶原 I 和 III 表达的影响,并评估了其对抑制 mTOR 信号通路的影响。我们的研究结果证实,与正常组织标本相比,瘢痕疙瘩中 mTOR 磷酸化水平升高。水飞蓟素处理显著降低了正常人类真皮和成纤维细胞来源的瘢痕疙瘩中胶原 I 和 III 的表达。这些作用伴随着 mTOR 信号通路的抑制。我们的研究结果表明,水飞蓟素作为一种有前途的治疗药物,具有预防和治疗瘢痕疙瘩的潜力。需要进一步的研究来探索水飞蓟素在瘢痕管理中的临床应用。