Ursolic acid inhibits Th17 cell differentiation via STAT3/RORγt pathway and suppresses Schwann cell-mediated Th17 cell migration by reducing CXCL9/10 expression

Xu, Haowen; Yu, Ai-Ling; Zhao, Dapeng; Meng, Guang-Yuan; Shan, Min Aung; Hu, Nai-Xia; Liu, Yunling

doi:10.1177/17534259221094559

Cited by 3 publications

(2 citation statements)

References 35 publications

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“…And small molecules targeting T-bet and RORγt also inhibit EAE (35). UA could reduce the serum levels of IL-6, IFN-γ, TNF-α and IL-17 (22,24,48). In the present study, UAOS-Na-treated EAE mice showed a significant reduction in serum levels of IFN-γ, TNF-α, IL-6, and IL-17A and in expression of key transcription factors T-bet and ROR-γt in spinal cord.…”

Section: Discussionsupporting

confidence: 57%

Ursolic acid derivative UAOS-Na treats experimental autoimmune encephalomyelitis by immunoregulation and protecting myelin

Wang,

Gu,

Yang

et al. 2023

Front. Neurol.

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IntroductionMultiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Ursolic acid (UA) can be used in the MS treatment with anti-inflammatory and neuroprotective activities. However, UA is insoluble in water, which may affect its medication effectiveness. In our previous study, UAOS-Na, a water-soluble derivative of UA was obtained. In this study, we evaluated the pharmacological effects and explored its underlying mechanism of UAOS-Na on experimental autoimmune encephalomyelitis (EAE).MethodsFirstly, the pharmacodynamics of UAOS-Na was investigated in EAE and Cuprizone-induced mice. And then the possible mechanisms were investigated by TMT proteomics and verified by in vitro and in vivo experiments.ResultsUAOS-Na (30 mg/kg/d) delayed the onset time of EAE from 11.78 days post immunization (dpi) to 14.33 dpi, reduced the incidence from 90.0% to 42.9%. UAOS-Na (60 mg/kg/d) reduced the serum levels of IFN-γ, IL-17A, TNF-α and IL-6, reduced the mononuclear cell infiltration of spinal cord, and inhibited the overexpression of key transcription factors T-bet and ROR-γt of EAE mouse spinal cord. In addition, UAOS-Na attenuated demyelination and astrogliosis in the CNS of EAE and cuprizone-induced mice. Mechanistically, proteomics showed that 96 differential expression proteins (DEPs) were enriched and 94 were upregulated in EAE mice compared with normal group. After UAOS-Na treatment, 16 DEPs were enriched and 15 were downregulated, and these DEPs were markedly enriched in antigen processing and presentation (APP) signaling pathway. Moreover, UAOS-Na downregulated the protein levels of Tapbp and H2-T23 in MHC-I antigen presentation pathway and reduced the proliferation of splenic CD8 T cells, thereby inhibiting the CNS infiltration of CD8 T cells.ConclusionOur findings demonstrated that UAOS-Na has both myelin protective and anti-inflammatory effects. And it could reduce the inflammation of MS by downregulating the expression of Tapbp and H2-T23 in the MHC-I antigen presentation pathway.

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Section: Discussionsupporting

confidence: 57%

Ursolic acid derivative UAOS-Na treats experimental autoimmune encephalomyelitis by immunoregulation and protecting myelin

Wang,

Gu,

Yang

et al. 2023

Front. Neurol.

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“…When cytokines, such as IL-6, IL-19, and IL-22, bind to their receptors, JAK is phosphorylated and binds to the cytokine receptor to make a receptor complex, resulting in the phosphorylation of downstream STAT3 at Tyr705 and Ser727, and the phospho-STAT3 meet to form dimers. These dimers bind to the nuclear DNA and regulate the expression of inflammatory proteins [ 44 , 45 ]. Western blotting showed that the expression levels of LPS-induced p-JAK1 and p-STAT3 were drastically reduced following FFE application ( Figure 5 ).…”

Section: Resultsmentioning

confidence: 99%

In Vitro and In Vivo Anti-Psoriasis Activity of Ficus carica Fruit Extracts via JAK-STAT Modulation

Lee,

Lee

2023

Life

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Psoriasis, a chronic and autoimmune inflammatory disorder of the skin, has been often underdiagnosed and underestimated despite its prevalence and considerable negative effects on the quality of life. In this study, the anti-inflammatory activity of Ficus carica fruit extract (FFE) was investigated against LPS-stimulated RAW 264.7 cells. The in vitro results showed that FFE reduced the production of nitric oxide (NO) and iNOS expression. Moreover, FFE reduced the level of β-hexosaminidase released with histamine in allergic reactions. However, the MAPK and NFκB signaling molecules associated with the inflammatory response were not significantly regulated by FFE. In contrast, the phosphorylation of JAK1 and STAT3 in the JAK–STAT signaling pathway was dramatically reduced by FFE treatment. Psoriasis-like skin lesions were induced in BALB/c mice using imiquimod (IMQ) to test the feasibility of FFE as a treatment for psoriasis. The efficacy of FFE was evaluated based on phenotypic and histological features. FFE was effective in relieving the symptoms of psoriasis-like skin lesions, such as erythema, dryness, scales, and thick epidermis. Notably, STAT3 modulation was also contributable to the in vivo ameliorative activity of FFE. Taken together, FFE with anti-psoriasis activity in vitro and in vivo through the JAK–STAT modulation could be developed as a therapeutic agent against psoriasis.

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Therapeutic effects and mechanism of action of lavender essential oil on atopic dermatitis by modulating the STAT3/RORγt pathway

Duan,

Li,

Wang

et al. 2024

Arabian Journal of Chemistry

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Ursolic acid inhibits Th17 cell differentiation via STAT3/RORγt pathway and suppresses Schwann cell-mediated Th17 cell migration by reducing CXCL9/10 expression

Cited by 3 publications

References 35 publications

Ursolic acid derivative UAOS-Na treats experimental autoimmune encephalomyelitis by immunoregulation and protecting myelin

Ursolic acid derivative UAOS-Na treats experimental autoimmune encephalomyelitis by immunoregulation and protecting myelin

In Vitro and In Vivo Anti-Psoriasis Activity of Ficus carica Fruit Extracts via JAK-STAT Modulation

Therapeutic effects and mechanism of action of lavender essential oil on atopic dermatitis by modulating the STAT3/RORγt pathway

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