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Research Article
Glycyrrhizin improves the pathogenesis of psoriasis through IL-17A and the SIRT1-STAT3 axis
Ying Ma
Huashan Hospital
Corresponding Author
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Background: The anti-inflammatory effect of glycyrrhizin has been widely recognized, while the specific mechanism of glycyrrhizin in psoriasis remains poorly understood.
Results: Here, in an imiquimd-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
Psoriasis, glycyrrhizin, IL-17A, SIRT1-STAT3 pathway
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CURRENT STATUS: Under Review
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Posted 16 Dec, 2020
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Review #1 received
Received 28 Dec, 2020
Review #2 received
Received 28 Dec, 2020
Review #3 received
Received 28 Dec, 2020
Reviewer #1 agreed
On 22 Dec, 2020
Reviewer #4 agreed
On 22 Dec, 2020
Reviewer #5 agreed
On 22 Dec, 2020
Reviewer #3 agreed
On 22 Dec, 2020
Reviewer #6 agreed
On 22 Dec, 2020
Reviewer #2 agreed
On 22 Dec, 2020
Reviewers invited
Invitations sent on 18 Dec, 2020
Editor assigned
On 17 Dec, 2020
Editor invited
On 15 Dec, 2020
Submission checks complete
On 15 Dec, 2020
First submitted
On 19 Nov, 2020
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Subject Areas
Dermatology
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This preprint is under consideration at BMC Immunology. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Glycyrrhizin improves the pathogenesis of psoriasis through IL-17A and the SIRT1-STAT3 axis
Ying Ma
Huashan Hospital
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 16 Dec, 2020
No community comments so far
Review #1 received
Received 28 Dec, 2020
Review #2 received
Received 28 Dec, 2020
Review #3 received
Received 28 Dec, 2020
Reviewer #1 agreed
On 22 Dec, 2020
Reviewer #4 agreed
On 22 Dec, 2020
Reviewer #5 agreed
On 22 Dec, 2020
Reviewer #3 agreed
On 22 Dec, 2020
Reviewer #6 agreed
On 22 Dec, 2020
Reviewer #2 agreed
On 22 Dec, 2020
Reviewers invited
Invitations sent on 18 Dec, 2020
Editor assigned
On 17 Dec, 2020
Editor invited
On 15 Dec, 2020
Submission checks complete
On 15 Dec, 2020
First submitted
On 19 Nov, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Dermatology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: The anti-inflammatory effect of glycyrrhizin has been widely recognized, while the specific mechanism of glycyrrhizin in psoriasis remains poorly understood.
Results: Here, in an imiquimd-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.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6