Licoisoflavone B alleviates psoriasis via SCD1-targeted lipid metabolism reprogramming and suppression of Th17/IL-17-mediated inflammation

  • Front Pharmacol. 2026 Feb 16:17:1754729. doi: 10.3389/fphar.2026.1754729.
Yao Liu  #  1  2 ,  Vincent Kam Wai Wong  #  2  3 ,  Jiao Liu  #  4  5 ,  Manling Jiang  #  4 ,  Chenxu Yang  2  3 ,  Xiang He  4 ,  Junyi Wang  4 ,  Lei Zhang  4 ,  Anying Xiong  4 ,  Qin Ran  4 ,  Xiaolan Li  4 ,  Keyue Wang  4 ,  Mufan Li  1  2 ,  Peng Song  1  2 ,  Liang Jin  1  2 ,  Guoping Li  1  2  4
Affiliations
  • 1. Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Mechanism and Quality of Chinese Medicine, Faculty of Chinese Medicine, Macau University of Science and Technology, Macao, China.
  • 2. Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Mechanism and Quality of Chinese Medicine, Macau University of Science and Technology, Macau, China.
  • 3. Macau University of Science and Technology Zhuhai MUST Science and Technology Research Institute, Macao, China.
  • 4. Laboratory of Allergy and Precision Medicine, Department of Respiratory Medicine, Chengdu Institute of Respiratory Health, Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, Chengdu, China.
  • 5. College of Medicine, Southwest Jiaotong University, Chengdu, China.
  • # Contributed equally.
PMID: 41777245 DOI: 10.3389/fphar.2026.1754729
Abstract

Introduction: Psoriasis is a chronic inflammatory skin disorder driven by dysregulated immune responses, Th17 cells activation, and keratinocytes hyperproliferation. Despite advances in therapies, high costs and adverse effects limit their utility. Licoisoflavone B (Lico B), bioactive flavonoid derived from licorice, exhibits anti-inflammatory and metabolic modulating properties, yet its mechanisms in psoriasis remain unexplored.

Methods: We employed integrative bioinformatics, including target prediction, differential expression analysis, and weighted gene co-expression network analysis to identify psoriasis-associated hub genes linked to Lico B. Functional enrichment was analyzed via GO and KEGG pathway. Molecular docking evaluated Lico B's binding affinity to candidate target. The effects of Lico B on Stearoyl-CoA Desaturase 1 (SCD1) expression, lipid metabolism, IL-17-induced keratinocyte proliferation, and Th17 differentiation.

Results: Bioinformatics revealed Lico B's targets were enriched in lipid metabolism and cell cycle pathways. SCD1 emerged as a key target, supported by strong binding affinity in docking studies. Experimentally, Lico B attenuated IL-17-induced SCD1 upregulation and lipid droplet accumulation in keratinocytes. It suppressed hyperproliferation markers (KRT17/Ki67) in cells and imiquimod-induced psoriatic mice. Furthermore, Lico B reduced Th17 differentiation and IL-17 production in murine models, demonstrating dual antiproliferative and immunomodulatory effects.

Conclusion: Lico B alleviates psoriasis by targeting SCD1 to modulate lipid metabolism, inhibit keratinocyte hyperproliferation, and dampen Th17/IL-17-driven inflammation. This multimodal mechanism positions Lico B as a novel therapeutic candidate for psoriasis and related inflammatory-metabolic dermatoses.

Keywords
Licoisoflavone B; lipidmetabolism; psoriasis; skin; stearoyl-CoA desaturase 1; traditional Chinese medicine.
Products