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.