2. Academic Validation
  3. Sappanone A ameliorated imiquimod-induced psoriasis-like dermatitis in BALB/c mice via suppressing Mmp8 expression and IL-17 signaling pathway

Sappanone A ameliorated imiquimod-induced psoriasis-like dermatitis in BALB/c mice via suppressing Mmp8 expression and IL-17 signaling pathway

  • Eur J Pharmacol. 2024 Jun 15:978:176746. doi: 10.1016/j.ejphar.2024.176746.
Hongyang Li 1,  Jingjing Xu 2,  Jun Liu 3,  Jiayi Li 1,  Man Xu 4,  Pengcheng Ma 1,  Lingjun Li 5,  Yurong Wang 6,  Cheng Wang 7
Affiliations

Affiliations

  • 1 Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, 210042, China.
  • 2 Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, 210042, China; School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, 210009, China.
  • 3 Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, 210042, China; Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing, 210009, China.
  • 4 The Department of Clinical Laboratory, The Fourth Affiliated Hospital of Nanjing Medical University, Nanjing, 210031, China.
  • 5 Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, 210042, China. Electronic address: lilj@pumcderm.cams.cn.
  • 6 School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, 210009, China. Electronic address: 1620154332@cpu.edu.cn.
  • 7 Department of Dermatology, Zhongda Hospital Southeast University, Nanjing, 210009, China. Electronic address: 101013253@seu.edu.cn.
PMID: 38880219 DOI: 10.1016/j.ejphar.2024.176746
Abstract

Psoriasis is a prevalent immune-mediated inflammatory skin disease characterized by excessive abnormal proliferation of keratinocytes and infiltration of immune cells, which have significant impact on the life quality of individuals. Although biological agents and small molecule targeted drugs have brought significant clinical benefits to psoriasis patients, adverse reactions and high prices remains key issues in clinical medication of psoriasis, while natural product monomers possess high efficiency, low toxicity, anti-inflammatory and immunomodulatory properties, and bring new hope for the clinical treatment of psoriasis. Sappanone A (SA), a small molecule compound isolated from Caesalpinia sappan L, exhibits significant anti-inflammatory properties in various models, such as kidney inflammation and LPS-induced mice inflammation. Among these effects, the anti-inflammatory property of SA has received significant attention. In our study, we found that SA exhibited anti-proliferation and anti-inflammatory effects in HaCaT cells, and significantly alleviated imiquimod-induced psoriasis-like skin lesions via the inhibition of the excessive proliferation of keratinocytes and the infiltration of lymphocytes. Furthermore, the combinational analysis of network pharmacology and transcriptome Sequencing revealed that SA exerted anti-psoriasis effects by inhibiting the matrix metalloproteinase 8 (Mmp8) expression and IL-17 pathway activation. In summary, we have first demonstrated that SA can be used as a novel anti-psoriasis drug, which may provide a novel strategy for the clinical treatment of psoriasis.

Keywords

IL-17 signaling pathway; Inflammatory response; Mmp8; Proliferation; Psoriasis; Sappanone A.

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