Phytomedicine. 2025 Nov 29. pii: S0944-7113(25)01232-2. [Epub ahead of print]150
157597
BACKGROUND: Psoriasis is a chronic inflammatory skin disease often referred to as the "incurable cancer," characterized by a long disease course, high recurrence rate, and inability to achieve complete cure. It not only severely impacts patients' quality of life but also faces challenges such as high treatment costs and side effects with current therapeutic approaches. The primary active component of pine pollen (PP) extract (PPE) is dihydroquercetin (DHQ), which possesses various pharmacological activities, including anti-inflammatory, antioxidant, and immune-modulating effects. To date, however, the pharmacological properties and mechanism of action of DHQ remain uncharacterised, and further evidence is required to substantiate its efficacy in treating psoriasis.
OBJECTIVE: This study sought to examine the anti-psoriatic properties of PPE, determine its principal active component, and clarify its mechanisms of action along with its therapeutic prospects.
METHOD: This study elucidated the anti-psoriatic mechanism of PPE. Bioactivity-directed purification afforded a PPE enriched with DHQ. Subsequent phytochemical analysis employing UPLC-Q-Orbitrap/MS and HPLC identified DHQ and 17 additional active constituents. The mechanism of action was predicted through an integration of network pharmacology and molecular docking, with predictions subsequently validated by RT-qPCR. In LPS-induced RAW 264.7 macrophages, a 24-hour intervention with PPE modulated levels of ROS, apoptosis, mitochondrial membrane potential, cell migration, and inflammatory responses. In a 5 % IMQ-induced murine psoriasis model, seven-day oral administration of PPE conferred therapeutic efficacy, as assessed by PASI scoring, histological and immunohistochemical examination, ELISA, and Western blot analysis.
RESULTS: PPE treatment significantly reduced PASI scores, skin thickness, splenic index, and inflammatory cell infiltration. It also reversed intestinal barrier damage, ameliorated small intestinal villus atrophy, and suppressed serum levels of inflammatory cytokines. PPE alleviated psoriasis by inhibiting macrophage-driven inflammation. Integrated UPLC-Q-Orbitrap/MS and HPLC analyses, combined with network pharmacology and molecular docking, identified DHQ as the primary active constituent of PPE. Consistent with Western blot and immunohistochemical findings, molecular analyses confirmed that PPE ameliorated IMQ-induced psoriasiform dermatitis and modulated Th17-related gene expression-including IL-17, IL-6, IL-1β, TNF-α, IFN-γ, and keratins. These results suggest that PPE exerts its therapeutic effect by modulating the IL-17 signalling pathway, mediated by HO-1/Nrf2, NF-κB, and JAK1/STAT3, which may represent critical targets in PPE-mediated treatment.
CONCLUSION: This study presents the first comprehensive investigation into the anti-psoriatic effects of PPE, wherein the complex mechanisms underlying its therapeutic action are elucidated. It is demonstrated that psoriatic inflammation and oxidative stress are alleviated by PPE, while immune function is modulated through regulation of the IL-23/Th17 axis and the Nrf2/HO-1, NF-κB, and JAK1/STAT3 signalling pathways. By extending beyond the specific compound and disease model under investigation, novel insights are provided that support the establishment of a new research paradigm for developing more effective clinical therapies.
Keywords: Dihydroquercetin; Immunological; Macrophage; Pinaceae; Pine pollen; Pinus massoniana Lamb.; Psoriasis