Zhang Yue, Ai Chen, Huang Fangzhou, Zhao Ji-Li, Ling Yixin, Chen Weijing, Li Zhenzhu, Wang Yu, Gao Fei, Li Siqi, Gao Wei, Wang Yu-Shuai
Department of Pharmacy, Anhui Engineering Technology Research Center of Biochemical Pharmaceutical, Bengbu Medical University, 2600 Donghai Avenue, Bengbu, 233030, China.
Photochem Photobiol Sci. 2025 Feb;24(2):293-306. doi: 10.1007/s43630-025-00692-0. Epub 2025 Mar 1.
β-Nicotinamide mononucleotide (NMN), as a precursor of long-lived protein co-factor nicotinamide adenine dinucleotide (NAD) in the human body, has demonstrated promising clinical value in treating photoaging and skin wounds. Previous research showed that NMN possessed significant skin protection against UVB-induced photoaging and promoted collagen synthesis. However, its potential mechanism remains unclear. This study aimed to investigate whether NMN improved UVB-induced collagen degradation by regulating ROS/MAPK/AP-1 signaling and stimulating mitochondrial proline biosynthesis. The results showed that NMN notably inhibited UVB-induced ROS production and down-regulated the MAPK/AP-1 signaling pathway. In addition, NMN significantly increased proline levels in mitochondria, which acted as the primary raw materials for collagen synthesis. Further mechanistic analysis revealed that NMN increased the levels of mitochondrial NAD and NADP(H). Besides, NMN supplementation activated pyrroline-5-carboxylatesynthetase (P5CS), a key enzyme in proline biosynthesis, by increasing SIRT3 levels. However, the promoting effects of NMN on proline and collagen synthesis were significantly inhibited when 3-TYP, a SIRT3 inhibitor, was combined applied. Meanwhile, the effects of NMN on collagen synthesis were reversed when the solute carrier family 25 member 51, a mammalian mitochondrial NAD transporter, was knocked down. Moreover, animal experiments indicated that NMN ameliorated UVB-induced collagen fiber degradation by activating the SIRT3/P5CS signaling. These results revealed that NMN could combat UVB-induced collagen depletion by regulating the ROS/MAPK/AP-1 and proline synthesis.
β-烟酰胺单核苷酸（NMN）作为人体中长寿蛋白辅因子烟酰胺腺嘌呤二核苷酸（NAD）的前体，在治疗光老化和皮肤伤口方面已显示出有前景的临床价值。先前的研究表明，NMN对紫外线B（UVB）诱导的光老化具有显著的皮肤保护作用，并能促进胶原蛋白合成。然而，其潜在机制仍不清楚。本研究旨在探讨NMN是否通过调节活性氧（ROS）/丝裂原活化蛋白激酶（MAPK）/活化蛋白-1（AP-1）信号通路和刺激线粒体脯氨酸生物合成来改善UVB诱导的胶原蛋白降解。结果表明，NMN显著抑制UVB诱导的ROS产生，并下调MAPK/AP-1信号通路。此外，NMN显著增加线粒体中的脯氨酸水平，脯氨酸是胶原蛋白合成的主要原料。进一步的机制分析表明，NMN增加了线粒体NAD和烟酰胺腺嘌呤二核苷酸磷酸（NADP(H)）的水平。此外，补充NMN通过增加沉默调节蛋白3（SIRT3）水平激活脯氨酸生物合成中的关键酶吡咯啉-5-羧酸合成酶（P5CS）。然而，当联合应用SIRT3抑制剂3-三氟甲氧基苯甲酰胺（3-TYP）时，NMN对脯氨酸和胶原蛋白合成的促进作用被显著抑制。同时，当敲低哺乳动物线粒体NAD转运体溶质载体家族25成员51时，NMN对胶原蛋白合成的作用被逆转。此外，动物实验表明，NMN通过激活SIRT3/P5CS信号改善UVB诱导的胶原纤维降解。这些结果表明，NMN可以通过调节ROS/MAPK/AP-1和脯氨酸合成来对抗UVB诱导的胶原蛋白消耗。
