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Kaixuan-Jiedu decoction ameliorates imiquimod-induced psoriasis-like skin lesions in mice by regulating S1P |
QIN Yeping, DAI Dan, XIAO Xue, SONG Ping |
(Department of Dermatology, Guang′anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China)
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Abstract Objective: To investigate the effects of Kaixuan-Jiedu decoction (KXJD) on psoriasis-like mice model and its regulation of S1P. Methods: Twenty-five BALB/c mice were randomly and equally divided into normal group, model group, methotrexate group, KXJD-M and KXJD-H group. In addition to the normal group, the psoriasislike mice model were established by external application of imiquimod in other groups, and samples were taken after 7 days of continuous intervention. During the period, the skin lesions were photographed and the psoriasis area and severity index (PASI) score was calculated; HE staining was used to observe the pathological changes of skin lesions and measure the thickness of epidermis; the spleen and thymus were photographed and weighed; the expression of Ki67 and S1P in epidermis was detected by immunohistochemistry; Western blotting assay was used to detect the expression of KRT17, Claudin and Occludin in skin lesions; the mRNA levels of IL-17, IL-23 and S1PRs were detected by qRT-PCR. Results: Compared with the model group, KXJD could alleviate the psoriatic skin lesions, reduce the PASI score and epidermal hyperplasia (both P<0.01), improve the index of thymus and spleen and vascular proliferation (P<0.01 or P<0.05), reduce the mRNA expression of inflammatory factors IL-17 and IL-23 (P<0.01), and repair the skin barrier (P<0.05). Meanwhile, KXJD could downregulate the expression of S1P and S1PRs mRNA in epidermis (P<0.05). Conclusion: KXJD could alleviate the symptoms of local skin lesions in psoriasis, and its possible mechanism may be related with the regulation of S1P.
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Received: 06 February 2023
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[1]Tang L, Yang X, Liang Y, et al. Transcription factor retinoidrelated orphan receptor γt: a promising target for the treatment of psoriasis[J]. Front Immunol, 2018, 9: 1210.
[2]de Oliveira PS, Pereira MC, Silva de Paula SK, et al. Increased IL17A, IFNG, and FOXP3 transcripts in moderatesevere psoriasis: a major influence exerted by IL17A in disease severity[J]. Mediators Inflamm, 2016, 2016: 4395276.
[3]Parisi R, Symmons DP, Griffiths CE, et al. Global epidemiology of psoriasis: a systematic review of incidence and prevalence[J]. J Invest Dermatol, 2013, 133(2): 377-385.
[4]Ding X, Wang T, Shen Y, et al. Prevalence of psoriasis in China: a populationbased study in six cities[J]. Eur J Dermatol, 2012, 22(5): 663-667.
[5]Armstrong AW, Read C. Pathophysiology, clinical presentation, and treatment of psoriasis: a review[J]. JAMA, 2020, 323(19): 1945-1960.
[6]Takeshita J, Grewal S, Langan SM, et al. Psoriasis and comorbid diseases: Epidemiology[J]. J Am Acad Dermatol, 2017, 76(3): 377-390.
[7]Wang H, Wang Z, Rani PL, et al. Identification of PTPN22, ST6GAL1 and JAZF1 as psoriasis risk genes demonstrates shared pathogenesis between psoriasis and diabetes[J]. Exp Dermatol, 2017, 26(11): 1112-1117.
[8]Parisi R, Iskandar IYK, Kontopantelis E, et al. National, regional, and worldwide epidemiology of psoriasis: systematic analysis and modelling study[J]. BMJ, 2020, 369: m1590.
[9]Nowowiejska J, Baran A, Flisiak I. Aberrations in lipid expression and metabolism in psoriasis[J]. Int J Mol Sci, 2021, 22(12): 6561.
[10]代丹, 陈艳华, 何春燕, 等. 基于靶向脂质组学探究开玄补肾法对寻常型银屑病的干预机制[J]. 中国实验方剂学杂志, 2023, 29(4): 117-125.
[11]Park JW, Park WJ, Futerman AH. Ceramide synthases as potential targets for therapeutic intervention in human diseases[J]. Biochim Biophys Acta, 2014, 1841(5): 671-681.
[12]Hait NC, Oskeritzian CA, Paugh SW, et al. Sphingosine kinases, sphingosine 1phosphate, apoptosis and diseases[J]. Biochim Biophys Acta, 2006, 1758(12): 2016-2026.
[13]Gardell SE, Dubin AE, Chun J. Emerging medicinal roles for lysophospholipid signaling[J]. Trends Mol Med, 2006, 12(2): 65-75.
[14]Kozowska D, HarasimSymbor E, Mys'liwiec H, et al. Serum sphingolipid level in psoriatic patients with obesity[J]. Postepy Dermatol Alergol, 2019, 36(6): 714-721.
[15]Chun J, Giovannoni G, Hunter SF. Sphingosine 1phosphate receptor modulator therapy for multiple sclerosis: differential downstream receptor signalling and clinical profile effects[J]. Drugs, 2021, 81(2): 207-231.
[16]宋坪, 王晓旭, 杨茂誉, 等. 开通玄府、通络解毒法治疗斑块状银屑病120例疗效观察[J]. 中医杂志, 2013, 54(17): 1476-1479.
[17]Sun L, Guo X, Qin Y, et al. Serum intestinal metabolites are rised in patients with psoriasis and metabolic syndrome[J]. Clin Cosmet Investig Dermatol, 2022, 15: 879-886.
[18]Boehncke WH, Schn MP. Psoriasis[J]. Lancet, 2015, 386(9997): 983-994.
[19]中华中医药学会皮肤科分会. 皮肤科分会银屑病中医治疗专家共识(2017年版)[J]. 中国中西医结合皮肤性病学杂志, 2018, 17(3): 273-277.
[20]Borodzicz S, Rudnicka L, MirowskaGuzel D, et al. The role of epidermal sphingolipids in dermatologic diseases[J]. Lipids Health Dis, 2016, 15: 13.
[21]Dai D, He C, Wang S, et al. Toward personalized interventions for psoriasis vulgaris: molecular subtyping of patients by using a metabolomics approach[J]. Front Mol Biosci, 2022, 9: 945917.
[22]Matloubian M, Lo CG, Cinamon G, et al. Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1[J]. Nature, 2004, 427(6972): 355-360.
[23]Schwab SR, Pereira JP, Matloubian M, et al. Lymphocyte sequestration through S1P lyase inhibition and disruption of S1P gradients[J]. Science, 2005, 309(5741): 1735-1739.
[24]Olsson T, Boster A, Fernández , et al. Oral ponesimod in relapsingremitting multiple sclerosis: a randomised phase Ⅱ trial[J]. J Neurol Neurosurg Psychiatry, 2014, 85(11): 1198-1208.
[25]Jin J, Xue N, Liu Y, et al. A novel S1P1 modulator IMMH002 ameliorates psoriasis in multiple animal models[J]. Acta Pharm Sin B, 2020, 10(2): 276-288.
[26]Blankenbach KV, Schwalm S, Pfeilschifter J, et al. Sphingosine1phosphate receptor2 antagonists: therapeutic potential and potential risks[J]. Front Pharmacol, 2016, 7: 167.
[27]Mys'liwiec H, Baran A, HarasimSymbor E, et al. Increase in circulating sphingosine1phosphate and decrease in ceramide levels in psoriatic patients[J]. Arch Dermatol Res, 2017, 309(2): 79-86.
[28]Olesch C, Ringel C, Brüne B, et al. Beyond immune cell migration: the emerging role of the sphingosine1phosphate receptor S1PR4 as a modulator of innate immune cell activation[J]. Mediators Inflamm, 2017, 2017: 6059203.
[29]Kunkel GT, Maceyka M, Milstien S, et al. Targeting the sphingosine1phosphate axis in cancer, inflammation and beyond[J]. Nat Rev Drug Discov, 2013, 12(9): 688-702.
[30]Aoki M, Aoki H, Ramanathan R, et al. Sphingosine1phosphate signaling in immune cells and inflammation: roles and therapeutic potential[J]. Mediators Inflamm, 2016, 2016: 8606878.
[31]van Doorn R, Lopes Pinheiro MA, Kooij G, et al. Sphingosine 1phosphate receptor 5 mediates the immune quiescence of the human brain endothelial barrier[J]. J Neuroinflammation, 2012, 9: 133.
[32]Moon SH, Kim JY, Song EH, et al. Altered levels of sphingosine and sphinganine in psoriatic epidermis[J]. Ann Dermatol, 2013, 25(3): 321-326.
[33]Checa A, Xu N, Sar DG, et al. Circulating levels of sphingosine1phosphate are elevated in severe, but not mild psoriasis and are unresponsive to antiTNFα treatment[J]. Sci Rep, 2015, 5: 12017.
[34]Shin SH, Cho KA, Hahn S, et al. Inhibiting sphingosine kinase 2 derivedsphingosine1phosphate ameliorates psoriasislike skin disease via blocking Th17 differentiation of nave CD4 T lymphocytes in mice[J]. Acta Derm Venereol, 2019, 99(6): 594-601.
[35]PérezJeldres T, Tyler CJ, Boyer JD, et al. Targeting cytokine signaling and lymphocyte traffic via small molecules in inflammatory bowel disease: JAK inhibitors and S1PR agonists[J]. Front Pharmacol, 2019, 10: 212.
[36]Garris CS, Wu L, Acharya S, et al. Defective sphingosine 1phosphate receptor 1 (S1P1) phosphorylation exacerbates TH17mediated autoimmune neuroinflammation[J]. Nat Immunol, 2013, 14(11): 1166-1172.
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. [J]. Journal of Jiangsu University(Medicine Edition), 2023, 33(02): 112-117. |
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