Dongsung Cancer Center, Dongsung Biopharmaceutical, Daegu 41061, Republic of Korea.
Int J Mol Sci. 2023 Aug 30;24(17):13468. doi: 10.3390/ijms241713468.
Skin photoaging due to ultraviolet B (UVB) exposure generates reactive oxygen species (ROS) that increase matrix metalloproteinase (MMP). Chlorin e6-photodynamic therapy (Ce6-PDT), in addition to being the first-line treatment for malignancies, has been shown to lessen skin photoaging, while curcumin is well known for reducing the deleterious effects of ROS. In the current study, PDT with three novel Ce6-curcumin derivatives, a combination of Ce6 and curcumin with various linkers, including propane-1,3-diamine for Ce6-propane-curcumin; hexane-1,6-diamine for Ce6-hexane-curcumin; and 3,3'-((oxybis(ethane-2,1-diyl))bis(oxy))bis(propan-1-amine) for Ce6-dipolyethylene glycol (diPEG)-curcumin, were studied for regulation of UVB-induced photoaging on human skin fibroblast (Hs68) and mouse embryonic fibroblast (BALB/c 3T3) cells. We assessed the antiphotoaging effects of Ce6-curcumin derivatives on cell viability, antioxidant activity, the mechanism of matrix metalloproteinase-1 and 2 (MMP-2) expression, and collagen synthesis in UVB-irradiated in vitro models. All three Ce6-curcumin derivatives were found to be non-phototoxic in the neutral red uptake phototoxicity test. We found that Ce6-hexane-curcumin-PDT and Ce6-propane-curcumin-associated PDT exhibited less cytotoxicity in Hs68 and BALB/c 3T3 fibroblast cell lines compared to Ce6-diPEG-curcumin-PDT. Ce6-diPEG-curcumin and Ce6-propane-curcumin-associated PDT showed superior antioxidant activity in Hs68 cell lines. Further, in UVB-irradiated in vitro models, the Ce6-diPEG-curcumin-PDT greatly attenuated the expression levels of MMP-1 and MMP-2 by blocking mitogen-activated protein kinases (MAPKs), activator protein 1 (AP-1), and tumor necrosis factor-α (NF-κB) signaling. Moreover, Ce6-diPEG-curcumin effectively inhibited inflammatory molecules, such as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression, while accelerating collagen synthesis. These results demonstrate that Ce6-diPEG-curcumin may be a potential therapy for treating skin photoaging.
由于紫外线 B（UVB）照射而导致的皮肤光老化会产生活性氧（ROS），从而增加基质金属蛋白酶（MMP）。氯乙酮 6-光动力疗法（Ce6-PDT）除了是恶性肿瘤的一线治疗方法外，还被证明可以减轻皮肤光老化，而姜黄素则以减少 ROS 的有害影响而闻名。在当前的研究中，使用三种新型的 Ce6-姜黄素衍生物（Ce6 与姜黄素与各种连接物的组合，包括丙烷-1,3-二胺用于 Ce6-丙烷-姜黄素；己烷-1,6-二胺用于 Ce6-己烷-姜黄素；和 3,3'-((氧双（乙烷-2,1-二基））双（氧基））双（丙烷-1-胺）用于 Ce6-二聚乙二醇（diPEG）-姜黄素），研究了它们对人皮肤成纤维细胞（Hs68）和小鼠胚胎成纤维细胞（BALB/c 3T3）细胞的 UVB 诱导光老化的调节作用。我们评估了 Ce6-姜黄素衍生物对细胞活力、抗氧化活性、基质金属蛋白酶-1 和 2（MMP-2）表达以及胶原合成的体外模型中的抗光老化作用。在中性红摄取光毒性试验中，发现三种 Ce6-姜黄素衍生物均无光毒性。我们发现，与 Ce6-diPEG-姜黄素-PDT 相比，Ce6-己烷-姜黄素-PDT 和 Ce6-丙烷-姜黄素相关 PDT 在 Hs68 和 BALB/c 3T3 成纤维细胞系中表现出更低的细胞毒性。Ce6-diPEG-姜黄素和 Ce6-丙烷-姜黄素相关 PDT 在 Hs68 细胞系中表现出更高的抗氧化活性。此外，在 UVB 照射的体外模型中，Ce6-diPEG-姜黄素-PDT 通过阻断丝裂原活化蛋白激酶（MAPKs）、激活蛋白 1（AP-1）和肿瘤坏死因子-α（NF-κB）信号通路，极大地降低了 MMP-1 和 MMP-2 的表达水平。此外，Ce6-diPEG-姜黄素有效抑制了炎症分子，如环加氧酶-2（COX-2）和诱导型一氧化氮合酶（iNOS）的表达，同时加速了胶原合成。这些结果表明，Ce6-diPEG-姜黄素可能是治疗皮肤光老化的一种潜在疗法。
