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A novel TGR5 agonist Sauchinone ameliorates IMQ induced murine psoriasis by regulating macrophage polarization

文献类型：期刊论文

作者Wang, Hao-yu1,2,6; Huang, Su-ling4; Ren, Jing3; Peng, Li-yan5; Chen, Lin-rui3; Qi, Lu-yao3,6; Zhu, Ke-han3,6; Feng, Chun-lan6; Zhou, Rong6; Gu, Yi-pei4
刊名JOURNAL OF ADVANCED RESEARCH
出版日期2026-02-01
卷号80页码:627-642
关键词Macrophage polarization Psoriasis Sauchinone TGR5
ISSN号2090-1232
DOI10.1016/j.jare.2025.04.034
英文摘要Introduction: G-protein-coupled bile acid receptor (TGR5) is a member of G-protein-coupled receptor (GPCR) superfamily that participates in regulating macrophage polarization and resolving inflammatory diseases. Sauchinone is Saururus chinensis derived natural product with anti-inflammatory activity. Still, whether Sauchinone could regulate macrophage polarization and its direct target remain to be explored. Objectives: This study aims to demonstrate the direct target of Sauchinone, its influences on macrophage polarization and its pharmacological actions on imiquimod (IMQ) induced mouse psoriasis model. Methods: We detected the TGR5 agonistic activity of Sauchinone in mouse/human TGR5/ cAMP response elements (CRE)/HEK293 stable cell lines and verified its direct effect on mouse/human macrophages by Cellular thermal shift assay (CETSA) and by examining downstream CREB phosphorylation. Afterwards, we discovered the activity of Sauchinone on regulating macrophage M1/M2 polarization in Bone marrow-derived macrophages (BMDM) by detecting M1/M2 markers through Enzyme-linked immunosorbent assay (ELISA), Real-time polymerase chain reaction (RT-qPCR), Western blot and Fluorescence-activated cell sorting (FACS). We further utilized macrophages derived from Tgr5-/-mice or introduced TGR5 specific inhibitor, TGR5 si-RNA and PKA inhibitor to determine whether Sauchinone regulated macrophage polarization through TGR5. We then prepared Sauchinone cream formulation to disclose its pharmacological action in IMQ induced mouse psoriasis model and used FACS and immunofluorescence to verify its action on macrophage polarization in psoriatic skin. Moreover, we tested the protective actions of Sauchinone cream in IMQ treated Tgr5-/-mice to verify that Sauchinone alleviated psoriasis in TGR5 dependent manner. Results: Sauchinone is a novel TGR5 agonist without human/mouse species selectivity. Sauchinone rectified macrophage M1 polarization through activating TGR5. Topical use of Sauchinone cream ameliorated IMQ induced psoriasis and regulated macrophage polarization in psoriatic skins. Sauchinone cream alleviated psoriasis in TGR5 dependent manner. Conclusion: Our work identified Sauchinone as a novel TGR5 agonist that could ameliorate IMQ induced murine psoriasis by regulating macrophage polarization. (c) 2025 The Authors. Published by Elsevier B.V. on behalf of Cairo University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
WOS关键词BILE-ACID RECEPTOR ; NF-KAPPA-B ; SAURURUS-CHINENSIS ; INTESTINAL MACROPHAGES ; ACTIVATION ; INHIBITION ; GPBAR1 ; LIGNAN ; DIFFERENTIATION ; INFLAMMATION
资助项目Strategic Priority Research Program of the Chinese Academy of Sciences[XDB1060000] ; National Natural Science Foundation of China[82173822]
WOS研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:001678657500010
出版者ELSEVIER
源URL[http://119.78.100.183/handle/2S10ELR8/322755]  
专题国家级研究中心_原创新药研究全国重点实验室
通讯作者Zhao, Qin-shi; Tang, Wei
作者单位1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
2.Nanjing Med Univ, Childrens Hosp, Dept Pharm, Nanjing 210008, Peoples R China
3.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
5.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochemistry & Plant Resources Wes, Kunming 650201, Peoples R China
6.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Chem Biol, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Wang, Hao-yu,Huang, Su-ling,Ren, Jing,et al. A novel TGR5 agonist Sauchinone ameliorates IMQ induced murine psoriasis by regulating macrophage polarization[J]. JOURNAL OF ADVANCED RESEARCH,2026,80:627-642.
APA Wang, Hao-yu.,Huang, Su-ling.,Ren, Jing.,Peng, Li-yan.,Chen, Lin-rui.,...&Tang, Wei.(2026).A novel TGR5 agonist Sauchinone ameliorates IMQ induced murine psoriasis by regulating macrophage polarization.JOURNAL OF ADVANCED RESEARCH,80,627-642.
MLA Wang, Hao-yu,et al."A novel TGR5 agonist Sauchinone ameliorates IMQ induced murine psoriasis by regulating macrophage polarization".JOURNAL OF ADVANCED RESEARCH 80(2026):627-642.

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来源：上海药物研究所

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