Oh Seyeon, Jeon Hee-Dae, Rho Nark-Kyoung, Son Kuk Hui, Byun Kyunghee
Functional Cellular Networks Laboratory, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Republic of Korea.
Banobagi Dermatology Clinic, Seoul 06109, Republic of Korea.
Int J Mol Sci. 2025 Jul 3;26(13):6399. doi: 10.3390/ijms26136399.
Ultraviolet (UV) radiation stimulates melanogenesis, leading to various esthetic problems. UV increases oxidative stress and nuclear factor-kappa B (NF-κB), which increase the nucleotide-binding oligomerization domain (NOD) or leucine-rich repeat and pyrin do-main containing 3 (NLRP3) inflammasome. Given that polydeoxyribonucleotides reduce melanogenesis and polynucleotide (PN) has molecular similarity to polydeoxyribonucleotides, we hypothesized that PN can decrease melanogenesis. We compared the anti-melanogenic effect of PN with that of a PN mixture (PNM) that contained other antioxidants, such as glutathione and hyaluronic acid, in UVB-irradiated keratinocytes and animal skin. PN and PNM both decreased oxidative stress, which was evaluated according to the expression of NADPH oxidase (NOX) 1/2/4, the glutathione (GSH):oxidized glutathione (GSSG) ratio, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in UVB-irradiated keratinocytes. The expression of NLRP3 inflammasome components (NLRP3, ASC, and pro-caspase-1) and IL-18 was increased by UVB radiation and reduced by PN and PNM. When conditioned media from PN or PNM were administered to UVB-radiated keratinocytes, melanogenesis-related signals (MITF, tyrosinase, and tyrosinase-related protein1/2) were decreased. These effects were similar in the UVB-irradiated animal skin. Both PN and PNM decreased melanin accumulation and increased skin lightness in UVB-irradiated skin. The anti-melanogenic effect of PNM was greater than that of PN. In conclusion, PN and PNM decreased melanogenesis by decreasing oxidative stress, NF-κB, and NLRP3 inflammasome activation.
紫外线(UV)辐射会刺激黑色素生成,引发各种美学问题。紫外线会增加氧化应激和核因子-κB(NF-κB),进而增加核苷酸结合寡聚化结构域(NOD)或含亮氨酸重复序列和吡啉结构域3(NLRP3)炎性小体。鉴于聚脱氧核糖核苷酸可减少黑色素生成,且多核苷酸(PN)与聚脱氧核糖核苷酸具有分子相似性,我们推测PN可以减少黑色素生成。我们在紫外线B(UVB)照射的角质形成细胞和动物皮肤中,比较了PN与含有其他抗氧化剂(如谷胱甘肽和透明质酸)的PN混合物(PNM)的抗黑色素生成作用。PN和PNM均降低了氧化应激,这是根据UVB照射的角质形成细胞中烟酰胺腺嘌呤二核苷酸磷酸氧化酶(NOX)1/2/4的表达、谷胱甘肽(GSH)与氧化型谷胱甘肽(GSSG)的比例以及8-羟基-2'-脱氧鸟苷(8-OHdG)来评估的。UVB辐射会增加NLRP3炎性小体成分(NLRP3、凋亡相关斑点样蛋白(ASC)和前半胱天冬酶-1)以及白细胞介素-18的表达,而PN和PNM可使其降低。当将来自PN或PNM的条件培养基施用于UVB照射的角质形成细胞时,黑色素生成相关信号(小眼畸形相关转录因子(MITF)、酪氨酸酶和酪氨酸酶相关蛋白1/2)会减少。这些作用在UVB照射的动物皮肤中相似。PN和PNM均减少了UVB照射皮肤中的黑色素积累并增加了皮肤亮度。PNM的抗黑色素生成作用大于PN。总之,PN和PNM通过降低氧化应激、NF-κB和NLRP3炎性小体的激活来减少黑色素生成。