Cucurbitacin B alleviates skin lesions and inflammation in a psoriasis mouse model by inhibiting the cGAS-STING signaling pathway.
- Author:
Yijian ZHANG
1
;
Xueting WANG
2
;
Yang YANG
3
;
Long ZHAO
3
;
Huiyang TU
4
;
Yiyu ZHANG
3
;
Guoliang HU
3
;
Chong TIAN
3
;
Beibei ZHANG
3
;
Zhaofang BAI
5
;
Bin ZHANG
6
,
7
Author Information
1. Anhui Medical University PLA 307 Clinical College, Beijing 100071; Senior Department of Hematology, the Fifth Medical Center of PLA General Hospital, Beijing 100071; Beijing Key Laboratory of Hematopoietic Stem Cell Therapy and Transformation Research, Beijing 100071; The Fifth Clinical Medical College of Anhui Medical University, Hefei 230032, China.
2. Senior Department of Hematology, the Fifth Medical Center of PLA General Hospital, Beijing 100071; Beijing Key Laboratory of Hematopoietic Stem Cell Therapy and Transformation Research, Beijing 100071; The School of Medicine, Nankai University, Tianjin 300071, China.
3. Senior Department of Hematology, the Fifth Medical Center of PLA General Hospital, Beijing 100071; Beijing Key Laboratory of Hematopoietic Stem Cell Therapy and Transformation Research, Beijing 100071, China.
4. Department of Oncology, Jiujiang No.1 People's Hospital, Jiujiang 332000, China.
5. Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Beijing 100071, China.
6. Anhui Medical University PLA 307 Clinical College, Beijing 100071; Senior Department of Hematology, the Fifth Medical Center of PLA General Hospital, Beijing 100071; Beijing Key Laboratory of Hematopoietic Stem Cell Therapy and Transformation Research, Beijing 100071; The Fifth Clinical Medical College of Anhui Medical University, Hefei 230032, China. *Corresponding author, E-mail: zb307ctc@
7. com.
- Publication Type:Journal Article
- MeSH:
Animals;
Psoriasis/pathology*;
Signal Transduction/drug effects*;
Membrane Proteins/genetics*;
Mice;
Nucleotidyltransferases/genetics*;
Disease Models, Animal;
Mice, Inbred BALB C;
Skin/metabolism*;
Triterpenes/therapeutic use*;
Humans;
Cytokines/metabolism*;
Inflammation/drug therapy*;
Male
- From:
Chinese Journal of Cellular and Molecular Immunology
2025;41(5):428-436
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of cucurbitacin B (CucB) on alleviating skin lesions and inflammation in psoriasis mice via the cGAS-STING signaling pathway. Methods The expression of genes associated with the cGAS-STING signaling pathway in psoriatic lesions and non-lesional skin was analyzed, and hallmark gene set enrichment analysis was performed. The cytotoxicity of CucB on BMDMs was evaluated using the CCK-8 assay. The expression levels of genes and proteins related to the cGAS-STING signaling pathway, along with the secretion of inflammatory cytokines, were measured at different concentrations of CucB using quantitative PCR, Western blotting, and ELISA. Imiquimod-induced psoriasis BALB/c mice were divided into four groups: normal group, model group, low-dose CucB group [0.1 mg/ (kg.d)], and high-dose CucB group [0.4 mg/ (kg.d)], with five mice per group. PASI scoring was performed to assess the severity of psoriasis after 6 days of treatment, and HE staining was conducted to observe pathological damage. Meanwhile, the mRNA levels of inflammatory cytokines and their secretion were detected by qPCR and ELISA. Results Most cGAS-STING signaling-related genes were upregulated in lesional skin of psoriasis patients, and the hallmark gene set enrichment analysis revealed that the most significantly upregulated genes were primarily associated with immune response signaling pathways. CucB inhibited dsDNA-induced phosphorylation of interferon regulatory factor 3 (IRF3) and STING proteins in both bone-marrow derived macrophages(BMDMs) and THP-1 cells. CucB also suppressed dsDNA-induced mRNA expression of IFNB1, TNF, IFIT1, CXCL10, ISG15, and reduced the secretion of cytokines such as IFN-β, IL-1β, and TNF-α in THP-1 cells. In the imiquimod-induced psoriasis mouse model, CucB treatment reduced psoriatic symptoms, alleviated skin lesions, and attenuated inflammation. ELISA and qPCR results showed that CucB significantly reduced serum secretion levels of IL-6, TNF-α, and IL-1β, as well as the mRNA levels of IL23A, IL1B, IL6, TNF, and IFNB1. Conclusion CucB inhibits cytoplasmic DNA-induced activationc of the GAS-STING pathway. CucB significantly attenuates skin lesions and inflammation in IMQ-induced psoriatic mice, and the potential molecular mechanism may be related to the down-regulation of the cGAS-STING pathway.
