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 in vitro model, and UVB-irradiated BALB/c nude mouse dorsal skin was established as an in vivo 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 via 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 in vitro and in vivo. 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.

#	Concept	H-Index	Publications	Citations
1	Medicine	1	1	20
2	Allergy	1	1	20
3	Pharmacology	1	1	20
4	Inflammation	1	1	20
5	Oxidative Stress	1	1	20

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