Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, Taibai North Road 229, Xi'an 710069, Shaanxi, China.
Shaanxi R & D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, Taibai North Road 229, Xi'an 710069, Shaanxi, China.
J Agric Food Chem. 2022 Dec 21;70(50):15804-15817. doi: 10.1021/acs.jafc.2c06377. Epub 2022 Dec 6.
Long-term exposure to ultraviolet (UV) irradiation, especially UVB, can trigger destructive intracellular effects, including various types of DNA damage, oxidative stress, and inflammatory responses, leading to accelerated skin aging. Ginsenoside Rk1, a rare ginsenoside pertaining to panaxadiol saponins, has been certified to possess underlying anti-inflammatory effects. Nevertheless, the efficiency of Rk1 against the photoaging of human skin and the latent molecular mechanisms are still unclear. Here, UVB-irradiated HaCaT keratinocytes were used as an model, and UVB-irradiated BALB/c nude mouse dorsal skin was established as an model to explore the mechanism by which Rk1 protects skin. Consequently, we found that Rk1 administration significantly attenuated oxidative stress by suppressing reactive oxygen species (ROS) overproduction and strengthening the activities of antioxidant enzymes. The UVB-induced inflammatory response was alleviated by Rk1 application regulation of the secretion of various proinflammatory cytokines. Additionally, western blot assays illustrated that Rk1 intervention inhibited collagen degradation by reducing the expression of matrix metalloproteinases. Further studies revealed that Rk1 could suppress the PI3K/AKT/NF-κB signaling pathways and . Molecular docking results indicated that Rk1 might effectively bind to the active pockets of PI3K, AKT, and NF-κB. The PI3K activator 740 Y-P clearly reversed the effects of Rk1 on oxidative stress, the inflammatory response, and collagen degradation in UVB-irradiated HaCaT cells. Moreover, histological and Masson staining verified that the administration of Rk1 to BALB/c nude mice remarkably ameliorated UVB-induced skin roughness, epidermal thickening, collagen fiber arrangement disorder, and wrinkles. Overall, the evidence provided in this study suggested that Rk1 could be applied for the development of effective natural antiphotoaging agents for skin health.
长期暴露于紫外线（UV）辐射，特别是 UVB，可引发破坏性的细胞内效应，包括各种类型的 DNA 损伤、氧化应激和炎症反应，导致皮肤加速老化。人参皂苷 Rk1 是一种属于人参二醇型皂苷的罕见皂苷，已被证实具有潜在的抗炎作用。然而，Rk1 对人皮肤光老化的功效及其潜在的分子机制尚不清楚。在这里，我们使用 UVB 照射的 HaCaT 角质形成细胞作为细胞模型，建立 UVB 照射的 BALB/c 裸鼠背部皮肤作为动物模型，以探讨 Rk1 保护皮肤的机制。结果发现，Rk1 给药可通过抑制活性氧（ROS）过度产生和增强抗氧化酶活性来显著减轻氧化应激。Rk1 的应用可通过调节各种促炎细胞因子的分泌来缓解 UVB 诱导的炎症反应。此外，Western blot 检测表明，Rk1 干预可通过降低基质金属蛋白酶的表达来抑制胶原降解。进一步的研究表明，Rk1 可以通过抑制 PI3K/AKT/NF-κB 信号通路来抑制胶原蛋白的降解。分子对接结果表明，Rk1 可能通过与 PI3K、AKT 和 NF-κB 的活性口袋有效结合来发挥作用。PI3K 激活剂 740 Y-P 可明显逆转 Rk1 对 UVB 照射的 HaCaT 细胞氧化应激、炎症反应和胶原降解的作用。此外，组织学和 Masson 染色验证了 Rk1 给药可显著改善 BALB/c 裸鼠的皮肤粗糙度、表皮增厚、胶原纤维排列紊乱和皱纹。总的来说，本研究提供的证据表明，Rk1 可用于开发有效的天然皮肤健康抗光老化剂。
