UPLC-Q-TOF/MS and network pharmacology identify β-sitosterol as a key component of Saussureae involucratae against epidermal barrier damage

Epidermal barrier damage represents a persistent challenge in dermatology, with limited treatment options currently available. Saussureae involucratae (SI) has demonstrated potential in dermatological applications, yet its bioactive constituents and underlying mechanisms remain largely unclear. This study employed an integrated approach combining ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS), network pharmacology, molecular docking, and experimental validation to identify key components of SI and their roles in mitigating epidermal barrier damage. Network pharmacology analysis identified 102 potential targets, with peroxisome proliferator-activated receptor gamma (PPAR-γ) emerging as a pivotal mediator of SI’s protective effects. In in vitro validation experiments, β-sitosterol—the key bioactive from SI—markedly eased oxidative stress by reducing reactive oxygen species (ROS) levels by approximately 52% under UVB irradiation ( p < 0.0001). It also boosted lipid synthesis by over 50% in UVB-exposed cells ( p = 0.0027), while upregulating PPAR-γ expression. These shifts curbed inflammation, improved hydration, and overall fortified the epidermal barrier against UVB insult. These findings suggest that SI may exerts protective effects against UVB-induced epidermal barrier dysfunction through multi-target mechanisms, with β-sitosterol as a key mediator. While the network pharmacology analysis provides valuable insights into potential mechanisms, these results are preliminary and need to be experimentally validated to confirm their relevance.