Anti‐inflammatory effects of amarogentin on 2,4‐dinitrochlorobenzene‐induced atopic dermatitis–like mice and in HaCat cells

Abstract Background Amarogentin (AMA) is a secoiridoid glycoside extracted from Swertia and Gentiana roots and exhibits many biological effects such as antioxidative, anti‐inflammatory, and antitumor activities. Atopic dermatitis (AD) is a chronic inflammatory skin disease caused by disorders in the...

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Main Authors: Qian Zhang, Hanlin Wang, Cheng Ran, Yansi Lyu, Fei Li, Yihang Yao, Shaojun Xing, Li Wang, Si Chen
Format: Article
Language:English
Published: Wiley 2023-06-01
Series:Animal Models and Experimental Medicine
Subjects:
Online Access:https://doi.org/10.1002/ame2.12260
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author Qian Zhang
Hanlin Wang
Cheng Ran
Yansi Lyu
Fei Li
Yihang Yao
Shaojun Xing
Li Wang
Si Chen
author_facet Qian Zhang
Hanlin Wang
Cheng Ran
Yansi Lyu
Fei Li
Yihang Yao
Shaojun Xing
Li Wang
Si Chen
author_sort Qian Zhang
collection DOAJ
description Abstract Background Amarogentin (AMA) is a secoiridoid glycoside extracted from Swertia and Gentiana roots and exhibits many biological effects such as antioxidative, anti‐inflammatory, and antitumor activities. Atopic dermatitis (AD) is a chronic inflammatory skin disease caused by disorders in the regulation of multiple inflammatory cytokines. No effective cure has been found for AD now. Methods We constructed the HaCat and splenocyte model and tested the inhibitory effect of AMA on IL‐4, IL‐6, and IL‐13 secretions using enzyme‐linked immunosorbent assay (ELISA). The AD mouse model was constructed and treated with AMA, the severity of skin lesions was observed, epidermal tissue was collected, and epidermal thickness and mast cell infiltration were observed using hematoxylin and eosin and toluidine blue staining, respectively. The expression of kallikrein‐related peptidase 7 (KLK7) and filaggrin (FLG) was detected using immunostaining and Western blot analysis. The mRNA expression of KLK7 and FLG was detected using quantitative polymerase chain reaction (qPCR). Blood immunoglobulin E (IgE) secretion was detected. Results AMA inhibited IL‐6 secreted by tumor necrosis factor (TNF)‐α‐induced HaCaT cells and reduced IL‐4 and IL‐13 secreted by phytohemagglutinin (PHA)‐induced primary cells in the mice spleen. It was found that the treatment of AMA with 2,4‐dinitrochlorobenzene‐induced AD‐like mice could promote the recovery of dermatitis, reduce the score of dermatitis severity and the scratching frequency, treat the skin lesions, reduce the epidermal thickness, decrease the infiltration of mast cells, reduce the IgE level in serum, decrease the expression levels of AD‐related cytokines, increase protein and mRNA expression of FLG, and reduce the protein and mRNA expression of KLK7 in the skin tissues of AD‐like mice. Conclusion In conclusion, AMA inhibits inflammatory response at the cellular level, and AMA reduces the validation response of specific dermatitis mice, relieves pruritus, and repairs the damaged skin barrier.
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spelling doaj.art-ef3c141633ba44cdbbb5c75dd2c3a9a62023-06-16T06:35:20ZengWileyAnimal Models and Experimental Medicine2576-20952023-06-016325526510.1002/ame2.12260Anti‐inflammatory effects of amarogentin on 2,4‐dinitrochlorobenzene‐induced atopic dermatitis–like mice and in HaCat cellsQian Zhang0Hanlin Wang1Cheng Ran2Yansi Lyu3Fei Li4Yihang Yao5Shaojun Xing6Li Wang7Si Chen8Department of Dermatology The Sixth Affiliated Hospital of Shenzhen University and Huazhong University of Science and Technology Union Shenzhen Hospital Shenzhen ChinaDepartment of Immunology Shenzhen University Health Science Center Shenzhen ChinaDepartment of Otolaryngology Affiliate Hospital of Hebei University Baoding ChinaDepartment of Dermatology Shenzhen University General Hospital, Shenzhen University Shenzhen ChinaDepartment of Dermatology The Sixth Affiliated Hospital of Shenzhen University and Huazhong University of Science and Technology Union Shenzhen Hospital Shenzhen ChinaDepartment of Immunology Shenzhen University Health Science Center Shenzhen ChinaDepartment of Pathogen Biology Shenzhen University Health Science Center Shenzhen ChinaDepartment of Dermatology Shenzhen University General Hospital, Shenzhen University Shenzhen ChinaDepartment of Immunology Shenzhen University Health Science Center Shenzhen ChinaAbstract Background Amarogentin (AMA) is a secoiridoid glycoside extracted from Swertia and Gentiana roots and exhibits many biological effects such as antioxidative, anti‐inflammatory, and antitumor activities. Atopic dermatitis (AD) is a chronic inflammatory skin disease caused by disorders in the regulation of multiple inflammatory cytokines. No effective cure has been found for AD now. Methods We constructed the HaCat and splenocyte model and tested the inhibitory effect of AMA on IL‐4, IL‐6, and IL‐13 secretions using enzyme‐linked immunosorbent assay (ELISA). The AD mouse model was constructed and treated with AMA, the severity of skin lesions was observed, epidermal tissue was collected, and epidermal thickness and mast cell infiltration were observed using hematoxylin and eosin and toluidine blue staining, respectively. The expression of kallikrein‐related peptidase 7 (KLK7) and filaggrin (FLG) was detected using immunostaining and Western blot analysis. The mRNA expression of KLK7 and FLG was detected using quantitative polymerase chain reaction (qPCR). Blood immunoglobulin E (IgE) secretion was detected. Results AMA inhibited IL‐6 secreted by tumor necrosis factor (TNF)‐α‐induced HaCaT cells and reduced IL‐4 and IL‐13 secreted by phytohemagglutinin (PHA)‐induced primary cells in the mice spleen. It was found that the treatment of AMA with 2,4‐dinitrochlorobenzene‐induced AD‐like mice could promote the recovery of dermatitis, reduce the score of dermatitis severity and the scratching frequency, treat the skin lesions, reduce the epidermal thickness, decrease the infiltration of mast cells, reduce the IgE level in serum, decrease the expression levels of AD‐related cytokines, increase protein and mRNA expression of FLG, and reduce the protein and mRNA expression of KLK7 in the skin tissues of AD‐like mice. Conclusion In conclusion, AMA inhibits inflammatory response at the cellular level, and AMA reduces the validation response of specific dermatitis mice, relieves pruritus, and repairs the damaged skin barrier.https://doi.org/10.1002/ame2.12260amarogentinatopic dermatitis–like micecytokinesHaCaT
spellingShingle Qian Zhang
Hanlin Wang
Cheng Ran
Yansi Lyu
Fei Li
Yihang Yao
Shaojun Xing
Li Wang
Si Chen
Anti‐inflammatory effects of amarogentin on 2,4‐dinitrochlorobenzene‐induced atopic dermatitis–like mice and in HaCat cells
Animal Models and Experimental Medicine
amarogentin
atopic dermatitis–like mice
cytokines
HaCaT
title Anti‐inflammatory effects of amarogentin on 2,4‐dinitrochlorobenzene‐induced atopic dermatitis–like mice and in HaCat cells
title_full Anti‐inflammatory effects of amarogentin on 2,4‐dinitrochlorobenzene‐induced atopic dermatitis–like mice and in HaCat cells
title_fullStr Anti‐inflammatory effects of amarogentin on 2,4‐dinitrochlorobenzene‐induced atopic dermatitis–like mice and in HaCat cells
title_full_unstemmed Anti‐inflammatory effects of amarogentin on 2,4‐dinitrochlorobenzene‐induced atopic dermatitis–like mice and in HaCat cells
title_short Anti‐inflammatory effects of amarogentin on 2,4‐dinitrochlorobenzene‐induced atopic dermatitis–like mice and in HaCat cells
title_sort anti inflammatory effects of amarogentin on 2 4 dinitrochlorobenzene induced atopic dermatitis like mice and in hacat cells
topic amarogentin
atopic dermatitis–like mice
cytokines
HaCaT
url https://doi.org/10.1002/ame2.12260
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