Journal of Inflammation Research (Aug 2023)

Resveratrol Ameliorates Imiquimod-Induced Psoriasis-Like Mouse Model via Reducing Macrophage Infiltration and Inhibiting Glycolysis

  • Wang Y,
  • Qi C,
  • Feng F,
  • Hu X,
  • Zhao N,
  • Zhao J,
  • Di T,
  • Meng Y,
  • Yang D,
  • Zhu H,
  • Zhang X,
  • Li P,
  • Wang Y

Journal volume & issue
Vol. Volume 16
pp. 3823 – 3836

Abstract

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Yazhuo Wang,1,2 Cong Qi,1,2 Fang Feng,3 Xueqing Hu,3 Ning Zhao,1,2 Jingxia Zhao,1 Tingting Di,1 Yujiao Meng,1 Danyang Yang,1,2 Haoyue Zhu,1,2 Xiawei Zhang,1,2 Ping Li,1 Yan Wang1 1Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing Institute of Traditional Chinese Medicine, Beijing Key Laboratory of Clinic and Basic Research with Traditional Chinese Medicine on Psoriasis, Beijing, People’s Republic of China; 2Capital Medical University, Beijing, 100069, People’s Republic of China; 3Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of ChinaCorrespondence: Ping Li; Yan Wang, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing Institute of Traditional Chinese Medicine, Beijing Key Laboratory of Clinic and Basic Research with Traditional Chinese Medicine on Psoriasis, Beijing, 100010, People’s Republic of China, Email [email protected]; [email protected]: Resveratrol (Res) is a natural polyphenol with anti-inflammatory and immunomodulatory effects. Alterations in metabolic pathways have been studied in psoriasis. This study is aimed to further explore the potential molecular mechanism of psoriasis improvement by Res.Patients and Methods: Imiquimod (IMQ)-induced psoriasis-like mouse model was established to observe the effects of Res. NanoString nCounter Metabolic Pathways Panel was used to analyze the changed mRNA and qRT-PCR was used for validation. Flow cytometry was used to analyze immune cell subsets in skin lesions. In vitro, we observed the effects of Res on R848-stimulated macrophages glycolysis and inflammation.Results: Res reduced the proliferation of keratinocytes and the secretion of inflammatory cytokines in IMQ-induced psoriasis-like mouse model. Psoriasis model skin lesions were in a state of hypoxia, with upregulated glycolysis and downregulated AMPK activity. Res inhibited the levels of hypoxia-related genes (hif1α, hif3α) and glycolysis-related genes (hk1, ldha), meanwhile increased the levels of AMPK genes (prkaa1, prkaa2). Flow cytometry analysis revealed that Res decreased the infiltration of macrophages in psoriasis-like lesions. In addition, Res decreased the secretion of macrophage-associated pro-inflammatory cytokines (IL-23, TNF-α, IL-1β). In vitro, Res diminished the secretion of IL-23, TNF-α, IL-1β, and lactate by R848-stimulated macrophages and activated AMPK.Conclusion: This study suggested that Res diminished psoriasis symptoms by inhibiting macrophages infiltration and inhibiting glycolysis, which providing novel insights into the underlying mechanisms of therapeutic action of Res in the treatment of psoriasis.Keywords: resveratrol, psoriasis, macrophage, AMPK, glycolysis

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