目的 通过超高效液相色谱-四极杆-飞行时间串联质谱联用仪（UPLC-Q-TOF-MS/MS）技术结合网络药理学预测与动物实验验证，探究红参须改善中波紫外线（ultraviolet b，UVB）诱导的皮肤光老化的药效物质基础及作用机制。方法 采用UPLC-Q-TOF-MS/MS技术鉴别红参须乳膏干预后小鼠皮肤滞留的原型成分，通过网络药理学筛选红参须抗光老化的关键活性成分、核心靶点及信号通路，构建UVB诱导的小鼠皮肤光老化模型，采用皮肤屏障功能检测、组织病理染色、氧化应激生化检测、Western blotting等技术，验证红参须的药效及通路调控作用。结果 从小鼠皮肤中共鉴定出13种人参皂苷类皮肤滞留活性成分；网络药理学预测提示磷脂酰肌醇3-激酶（phosphatidylinositol 3-kinase，PI3K）/蛋白激酶B（protein kinase B，Akt）信号通路为红参须抗光老化核心调控通路。动物实验结果表明，红参须可显著修复光老化小鼠皮肤屏障损伤，改善皮肤皱纹、色素异常等外观改变，使紊乱的表皮层次恢复规整、缓解真皮胶原降解流失；显著上调谷胱甘肽过氧化物酶（glutathione peroxidase，GSH-Px）、超氧化物歧化酶1（superoxide dismutase 1，SOD1）、血红素氧合酶-1（heme oxygenase-1，HO-1）抗氧化水平（P＜0.05、0.01、0.001），并增加羟脯氨酸（hydroxyproline，Hyp）含量（P＜0.05、0.001），降低脂质过氧化产物丙二醛（malondialdehyde，MDA）含量（P＜0.05、0.01）；下调基质金属蛋白酶2（matrix metallopeptidase 2，MMP2）、MMP9异常表达（P＜0.01、0.001），调控凝血酶敏感蛋白-1（thrombospondin-1，TSP-1）、血管内皮生长因子（vascular endothelial growth factor，VEGF）、环氧化酶-2（cyclooxygenase-2，COX-2）的表达（P＜0.05、0.001），平衡炎症反应与异常血管新生，同时显著抑制PI3K、Akt的过度磷酸化（P＜0.05、0.01）。结论 红参须以皮肤滞留人参皂苷为物质基础，通过修复皮肤屏障、抗氧化、抗炎、抑制胶原降解和异常血管生成，并调控PI3K/Akt信号通路，改善UVB诱导的皮肤光老化。

Objective To explore the pharmacodynamic material basis and mechanism of red ginseng fibrous roots in improving ultraviolet B (UVB)-induced skin photoaging by using ultra-high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) combined with network pharmacology prediction and animal experimental verification. Methods UPLC-Q-TOF-MS/MS was used to identify the prototype components retained in the skin of mice treated with red ginseng fibrous roots cream. Network pharmacology was applied to screen the key anti-photoaging active components, core targets and signaling pathways of red ginseng fibrous roots. A mouse model of UVB-induced skin photoaging was established, and multiple techniques including skin barrier function tests, histopathological staining, oxidative stress biochemical assays and Western blotting were adopted to verify the efficacy of red ginseng fibrous roots and its regulatory effect on related pathways. Results A total of 13 ginsenoside-type skin-retained active components were identified from mouse skin. Network pharmacology prediction indicated that the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway served as the core regulatory pathway of red ginseng fibrous roots against photoaging. Animal experiments showed that red ginseng fibrous roots could significantly repair skin barrier damage in photoaging mice, improve appearance changes such as skin wrinkles and pigment abnormalities, restore disordered epidermal layers to normal, and alleviate the degradation and loss of dermal collagen. Red ginseng fibrous roots significantly up-regulated the antioxidant levels of glutathione peroxidase (GSH-Px), superoxide dismutase 1 (SOD1) and heme oxygenase-1 (HO-1) (P < 0.05, 0.01, 0.001), increased the content of hydroxyproline (Hyp) (P < 0.05, 0.001), and decreased the content of lipid peroxidation product malondialdehyde (MDA) (P < 0.05, 0.01). Red ginseng fibrous roots down-regulated the abnormal expressions of matrix metalloproteinase2 (MMP2) and MMP9 (P < 0.01, 0.001), regulated the expressions of thrombospondin-1 (TSP-1), vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) to balance inflammation and abnormal angiogenesis (P < 0.05, 0.001). Red ginseng fibrous roots significantly inhibited the excessive phosphorylation of PI3K and Akt proteins (P < 0.05, 0.01). Conclusion Red ginseng fibrous roots, with skin-retained ginsenosides as the material basis, improve UVB-induced skin photoaging by repairing the skin barrier, exerting antioxidant and anti-inflammatory effects, inhibiting collagen degradation and abnormal angiogenesis, and regulating PI3K/Akt signaling pathway.

R285.5

国家自然科学基金资助项目（81602773）；天津市自然科学基金重点项目（24JCZDJC00720）；现代中医药海河实验室科技计划项目（24HHZYSS00009）；天津中医药大学研究生科研创新项目（YJSKC-20250027）