Glycyrrhizic acid and patchouli alcohol in Huoxiang Zhengqi attenuate intestinal inflammation and barrier injury via regulating endogenous corticosterone metabolism mediated by 11β-HSD1
文献类型：期刊论文
| 作者 | Wang, Yangyang4,5; Sun, Chuying6; Cao, Yutang6; Jiao, Tingying5,7; Wang, Kanglong5; Li, Jiaqi5,8; Zhang, Mengjiao6; Jiang, Jie1; Zhong, Xianchun5; Yu, Shuwu5 |
| 刊名 | JOURNAL OF ETHNOPHARMACOLOGY
 |
| 出版日期 | 2025-02-10 |
| 卷号 | 338页码:17 |
| 关键词 | Huoxiang Zhengqi Glycyrrhizic acid Patchouli alcohol Inflammation Intestinal barrier injury 11 beta-hydroxysteroid dehydrogenase 1 |
| ISSN号 | 0378-8741 |
| DOI | 10.1016/j.jep.2024.119025 |
| 通讯作者 | Huang, Chenggang(cghuang@simm.ac.cn) ; Wu, Tong(wutong1@sinopharm.com) ; Guo, Xiaozhen(guoxz@simm.ac.cn) ; Xie, Cen(xiecen@simm.ac.cn) |
| 英文摘要 | Ethnopharmacological relevance: Ulcerative colitis (UC), a chronic inflammatory bowel disease, has become a significant public health challenge due to the limited effectiveness of available therapies. Huoxiang Zhengqi (HXZQ), a well-established traditional Chinese formula, shows potential in managing UC, as suggested by clinical and pharmacological studies. However, the active components and mechanisms responsible for its effects remain unclear. Aim of study: This study aimed to identify the bioactive components of HXZQ responsible for its therapeutic effects on UC and to elucidate their underlying mechanisms. Materials and methods: The effect of HXZQ against dextran sodium sulfate (DSS)-induced colitis was investigated. Ingredients in HXZQ were characterized and analyzed in colitic mice using liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). In vitro, biological activity of compounds was assessed using lipopolysaccharide (LPS)-induced Ana-1 cells and bone marrow-derived macrophages (BMDMs), tumor necrosis factor-alpha (TNF-alpha)-induced Caco-2 cells, and isolated intestinal crypts from colitic mice. These results were confirmed in vivo. The targets of the components were identified through bioinformatics analysis and validated via molecular docking, enzyme inhibition assays, and in vivo experiments. Hematoxylin and eosin (HE) staining, periodic acid-Schiff (PAS) staining, immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), western blotting, and quantitative real-time polymerase chain reaction (qPCR) were employed to confirm the pharmaceutical effects. Results: A clinical equivalent dose of HXZQ (2.5 mL/kg) effectively treated DSS-induced colitis. A total of 113 compounds were identified in HXZQ, with 35 compounds detected in colitic mice. Glycyrrhizic acid (GA) and patchouli alcohol (PA) emerged as key contributors to the anti-colitic effects of HXZQ. Further investigation revealed that HXZQ and its active components decreased the levels of pro-inflammatory cytokines TNF-alpha, interleukin-1(3 (IL-1(3), and interleukin-6 (IL-6) in colon, likely by inhibiting nuclear factor kappa-B (NF-kappa B) signaling pathway. This inhibition indirectly activated the intestinal farnesoid X receptor (FXR) signaling pathway, correcting bile acid imbalances caused by colitis. Additionally, these components significantly enhanced the expression of tight junction proteins ZO-1 and Occludin, as well as the adhesion protein E-cadherin, and reduced goblet cell loss, thereby repairing intestinal barrier injury. Mechanistically, GA and PA were found to inhibit 11(3-hydroxysteroid dehydrogenase 1 (11(3-HSD1) activity, leading to increased local active corticosterone levels in the intestine to exert anti-inflammatory effects. Notably, the inhibition of 11(3-HSD1 with the selective inhibitor BVT2733 (BVT) ameliorated colitis in mice. Conclusions: HXZQ exhibits therapeutic effects on UC, primarily through GA and PA inhibiting 11(3-HSD1. This suggests new natural therapy approaches for UC and positions 11(3-HSD1 as a potential target for colitis treatment. |
| WOS关键词 | 11-BETA-HYDROXYSTEROID DEHYDROGENASE ; INDUCED COLITIS ; EXPRESSION |
| 资助项目 | National Key Research and Development Program of China[2021YFA1301200] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB39020600] ; National Natural Science Foundation of China[82222071] ; National Natural Science Foundation of China[82104253] ; Shanghai Municipal Science and Technology Major Project |
| WOS研究方向 | Plant Sciences ; Pharmacology & Pharmacy ; Integrative & Complementary Medicine |
| 语种 | 英语 |
| WOS记录号 | WOS:001356649900001 |
| 出版者 | ELSEVIER IRELAND LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/314536]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Huang, Chenggang; Wu, Tong; Guo, Xiaozhen; Xie, Cen |
| 作者单位 | 1.Shanghai Univ Tradit Chinese Med, Longhua Hosp, Div Nephrol, Shanghai, Peoples R China 2.Fudan Univ, Sch Pharm, Dept Biol Med, Shanghai 201023, Peoples R China 3.Fudan Univ, Shanghai Engn Res Ctr Immunotherapeut, Sch Pharm, Shanghai 200032, Peoples R China 4.Shanghai Inst Pharmaceut Ind, Natl Key Lab Lead Druggabil Res, Shanghai 201203, Peoples R China 5.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 6.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China 7.Fudan Univ, Human Phenome Inst, Sch Life Sci, State Key Lab Genet Engn, Shanghai, Peoples R China 8.Univ Chinese Acad Sci, Beijing 100049, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Yangyang,Sun, Chuying,Cao, Yutang,et al. Glycyrrhizic acid and patchouli alcohol in Huoxiang Zhengqi attenuate intestinal inflammation and barrier injury via regulating endogenous corticosterone metabolism mediated by 11β-HSD1[J]. JOURNAL OF ETHNOPHARMACOLOGY,2025,338:17. |
| APA | Wang, Yangyang.,Sun, Chuying.,Cao, Yutang.,Jiao, Tingying.,Wang, Kanglong.,...&Xie, Cen.(2025).Glycyrrhizic acid and patchouli alcohol in Huoxiang Zhengqi attenuate intestinal inflammation and barrier injury via regulating endogenous corticosterone metabolism mediated by 11β-HSD1.JOURNAL OF ETHNOPHARMACOLOGY,338,17. |
| MLA | Wang, Yangyang,et al."Glycyrrhizic acid and patchouli alcohol in Huoxiang Zhengqi attenuate intestinal inflammation and barrier injury via regulating endogenous corticosterone metabolism mediated by 11β-HSD1".JOURNAL OF ETHNOPHARMACOLOGY 338(2025):17. |
入库方式： OAI收割
来源：上海药物研究所
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