Glycyrrhizin improves the pathogenesis of psoriasis partially through IL-17A and the SIRT1-STAT3 axis

  • BMC Immunol. 2021 May 27;22(1):34. doi: 10.1186/s12865-021-00421-z.
Huang Qiong   #  1 ,  Ling Han   #  1 ,  Nanxue Zhang   #  1 ,  Huyan Chen  1 ,  Kexiang Yan  1 ,  Zhenghua Zhang  1 ,  Ying Ma  2 ,  Jinhua Xu  3
Affiliations
  • 1. Department of Dermatology, Huashan Hospital Affiliated to Fudan University, Shanghai, 200040, China.
  • 2. Department of Dermatology, Huashan Hospital Affiliated to Fudan University, Shanghai, 200040, China. [email protected].
  • 3. Department of Dermatology, Huashan Hospital Affiliated to Fudan University, Shanghai, 200040, China. [email protected].
  • # Contributed equally.
PMID: 34044769 DOI: 10.1186/s12865-021-00421-z
Abstract

Background: The anti-inflammatory effect of glycyrrhizin has been widely recognized, while the specific mechanism of glycyrrhizin in psoriasis remains poorly understood.

Results: In the imiquimod-induced mouse model of psoriasis (IMD), we found that glycyrrhizin can substantially improve the adverse symptoms in mice. The hematoxylin-eosin staining results showed that glycyrrhizin can also improve the pathological state of skin cells in IMD mice. Using enzyme-linked immunosorbent assay (ELISA), we found that glycyrrhizin substantially inhibited the expression of IL-17A and IFN-γ in the serum of IMD mice. In order to simulate the effect of IL-17A on keratinocytes in psoriasis, we treated HaCaT cells with 100 ng/mL IL-17A (IL-17A-HaCaT cells) for 48 h. Then, using cell-counting kit-8 (CCK-8) and ELISA assays, we found that glycyrrhizin inhibited the proliferation of IL-17A-HaCaT cells and reversed the promotion of IL-6, CCL20, and TNF-α induced by IL-17A. Further, western blotting (WB) results indicated that glycyrrhizin promoted the expression of SIRT1 and inhibited the expression of STAT3 and phosphorylated STAT3 (p-STAT3). By treating IL-17A-HaCaT cells with EX-527 (a potent and selective inhibitor of SIRT1), combined with CCK-8 and WB experiments, we initially found that EX-527 inhibited the proliferation of IL-17A-HaCaT cells and promoted the expression of STAT3, p-STAT3, and acetylated STAT3 (a-STAT3). However, when glycyrrhizin was added at the same time, the proliferation of IL-17A-HaCaT cells increased, and the expression of STAT3, p-STAT3, and a-STAT3 reduced. We then knocked down the expression of SIRT1 via small interfering RNA in IL-17A-HaCaT cells, and the results were consistent with those of EX-527.

Conclusions: Together, these results indicated that glycyrrhizin improved psoriasis by inhibiting the expression of IL-17A and IFN-γ in vivo and suppressed the proliferation of IL-17A-HaCaT cells and the expression of STAT3, p-STAT3, and a-STAT3 by upregulating SIRT1 in vitro.

Keywords
Glycyrrhizin; IL-17A; Psoriasis; SIRT1-STAT3 pathway.
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