Abstract

Background: Solar dermatitis (SD) is an inflammatory skin disease caused by excessive exposure to ultraviolet (UV) radiation. Gastrodia elata (GE) is a medicinal and edible plant with broad pharmacological activities; however, the polarity distribution of its active components and their specific mechanisms of action in SD remain incompletely understood. Methods: Different polarity fractions of GE-petroleum ether extract (PEE), ethyl acetate extract (EAE), and n-butanol extract (NBAE) were prepared and evaluated in a UVB-induced SD mouse model. We integrated metabolomics, network pharmacology, molecular docking, molecular dynamics simulations, and molecular biology techniques to identify key active ingredients and regulatory mechanisms. Results: The EAE group significantly ameliorated epidermal thickening and collagen damage in SD mice. Mechanistically, EAE and its active component luteolin (LUT) likely suppressed abnormal activation of the JUN pathway (binding energy: −9.1 kcal/mol), leading to downregulation of the pro-inflammatory cytokines tumour necrosis factor-alpha and inerleukin-1 beta. Conclusions: The EAE fraction alleviates SD through multi-component, multitarget synergistic effects, with LUT as a core bioactive component that inhibits the JUN pathway to mitigate skin inflammation and oxidative damage. EAE also accelerated SD recovery by modulating critical metabolic pathways, including arginine biosynthesis and terpenoid backbone biosynthesis. These findings identify EAE and LUT as promising candidate therapeutics for SD.

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