Gentiopicroside ameliorates psoriasis-like skin lesions in mice via regulating the Keap1-Nrf2 pathway and inhibiting keratinocyte activation
文献类型：期刊论文
| 作者 | Ren, Jing3,4; Chen, Xin3,4; Wang, Hao-yu2,3; Yang, Tao2,3; Zhang, Kai-rong1; Lei, Shu-yue2,3; Qi, Lu-yao3,4; Feng, Chun-lan3; Zhou, Rong3; Zhou, Hu2,3,4
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| 刊名 | ACTA PHARMACOLOGICA SINICA
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| 出版日期 | 2025-01-08 |
| 页码 | 14 |
| 关键词 | psoriasis gentiopicroside keratinocyte oxidative stress Keap1-Nrf2 pathway calcipotriol |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/s41401-024-01449-8 |
| 通讯作者 | Zhou, Hu(zhouhu@simm.ac.cn) ; Tang, Wei(tangwei@simm.ac.cn) |
| 英文摘要 | Psoriasis is a chronic, systemic immune-mediated skin disease. Although many new strategies for psoriasis treatment have been developed, there is great need in clinic for treating psoriasis. Gentiopicroside (GPS), derived from Gentiana manshurica Kitagawa, has multiple pharmacological activities including anti-inflammatory, anti-oxidative and antiviral activities. In this study, we investigated the potential effects of GPS in imiquimod (IMQ)-induced psoriasis mouse model and the underlying mechanisms. The mice were sensitized on their shaved back with IMQ cream for 7 days with or without topical application of 1% or 2% GPS cream. We showed that the application of GPS cream significantly ameliorated psoriasis-like skin lesions; GPS effect was better than that of calcipotriol. GPS rectified the immune cells infiltration and keratinocytes activation in the skin lesions, and significantly inhibited TNF-alpha/IFN-gamma stimulated human keratinocyte (HaCaT) activation in vitro. Proteomic analysis from keratinocytes with and without GPS treatment prompted that GPS regulated the Keap1-Nrf2 pathway, which was the most important pathway in regulating oxidative stress and inflammation. We demonstrated that GPS regulated the protein expression of p62 and Keap1, induced Nrf2 nuclear translocation followed by transcription of Nrf2 downstream antioxidant genes in HaCaT cells. Furthermore, the antioxidant effects of GPS were abolished in Nrf2-/- keratinocytes. Simultaneously, Nrf2-/- mice showed increased psoriasiform symptoms with a diminished protective effect in response to GPS treatment. Collectively, the study discloses that GPS inhibits keratinocyte activation and ameliorates psoriasis-like skin lesions in an Nrf2-dependent manner. |
| WOS关键词 | DERMATITIS ; AUTOPHAGY ; TARGET |
| 资助项目 | Strategic Priority Research Program of the Chinese Academy of Sciences[XDB1060000] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001391808400001 |
| 出版者 | NATURE PUBL GROUP |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/315570]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Zhou, Hu; Tang, Wei |
| 作者单位 | 1.Nanchang Univ, Sch Pharmaceut Sci, Nanchang 330006, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Chem Biol, Shanghai 201203, Peoples R China 4.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China |
| 推荐引用方式 GB/T 7714 | Ren, Jing,Chen, Xin,Wang, Hao-yu,et al. Gentiopicroside ameliorates psoriasis-like skin lesions in mice via regulating the Keap1-Nrf2 pathway and inhibiting keratinocyte activation[J]. ACTA PHARMACOLOGICA SINICA,2025:14. |
| APA | Ren, Jing.,Chen, Xin.,Wang, Hao-yu.,Yang, Tao.,Zhang, Kai-rong.,...&Tang, Wei.(2025).Gentiopicroside ameliorates psoriasis-like skin lesions in mice via regulating the Keap1-Nrf2 pathway and inhibiting keratinocyte activation.ACTA PHARMACOLOGICA SINICA,14. |
| MLA | Ren, Jing,et al."Gentiopicroside ameliorates psoriasis-like skin lesions in mice via regulating the Keap1-Nrf2 pathway and inhibiting keratinocyte activation".ACTA PHARMACOLOGICA SINICA (2025):14. |
入库方式： OAI收割
来源：上海药物研究所
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