PMID- 36131559 OWN - NLM STAT- MEDLINE DCOM- 20230619 LR - 20230619 IS - 2576-2095 (Electronic) IS - 2096-5451 (Print) IS - 2576-2095 (Linking) VI - 6 IP - 3 DP - 2023 Jun TI - Anti-inflammatory effects of amarogentin on 2,4-dinitrochlorobenzene-induced atopic dermatitis-like mice and in HaCat cells. PG - 255-265 LID - 10.1002/ame2.12260 [doi] AB - 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)-alpha-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. CI - (c) 2022 The Authors. Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences. FAU - Zhang, Qian AU - Zhang Q AUID- ORCID: 0000-0003-4516-3455 AD - Department of Dermatology, The Sixth Affiliated Hospital of Shenzhen University and Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, China. FAU - Wang, Hanlin AU - Wang H AD - Department of Immunology, Shenzhen University Health Science Center, Shenzhen, China. FAU - Ran, Cheng AU - Ran C AD - Department of Otolaryngology, Affiliate Hospital of Hebei University, Baoding, China. FAU - Lyu, Yansi AU - Lyu Y AD - Department of Dermatology, Shenzhen University General Hospital, Shenzhen University, Shenzhen, China. FAU - Li, Fei AU - Li F AD - Department of Dermatology, The Sixth Affiliated Hospital of Shenzhen University and Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, China. FAU - Yao, Yihang AU - Yao Y AD - Department of Immunology, Shenzhen University Health Science Center, Shenzhen, China. FAU - Xing, Shaojun AU - Xing S AD - Department of Pathogen Biology, Shenzhen University Health Science Center, Shenzhen, China. FAU - Wang, Li AU - Wang L AD - Department of Dermatology, Shenzhen University General Hospital, Shenzhen University, Shenzhen, China. FAU - Chen, Si AU - Chen S AD - Department of Immunology, Shenzhen University Health Science Center, Shenzhen, China. LA - eng GR - 2021042/Hospital Project of Huazhong University of Science and Technology Union Shenzhen Hospital/ GR - 86000000210/SZU Top Ranking Project/ GR - 20200812211704001/Shenzhen Science and Technology Innovation Committee/ GR - JCY20180305124849781/Shenzhen Science and Technology Innovation Committee/ GR - A2019502/Medical Scientific Research Foundation of Guangdong Province/ GR - 82078189/National Natural Science Foundation of China/ GR - 81902067/National Natural Science Foundation of China/ PT - Journal Article DEP - 20220921 PL - United States TA - Animal Model Exp Med JT - Animal models and experimental medicine JID - 101726292 RN - 0 (Dinitrochlorobenzene) RN - 5L82GT5I0W (amarogentin) RN - 0 (Interleukin-13) RN - 0 (Interleukin-6) RN - 207137-56-2 (Interleukin-4) RN - 0 (Cytokines) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Anti-Inflammatory Agents) RN - 37341-29-0 (Immunoglobulin E) RN - 0 (RNA, Messenger) SB - IM MH - Animals MH - Mice MH - Humans MH - *Dermatitis, Atopic/chemically induced/drug therapy/metabolism MH - Dinitrochlorobenzene/adverse effects MH - Interleukin-13/adverse effects MH - Interleukin-6/adverse effects MH - HaCaT Cells/metabolism/pathology MH - Interleukin-4/adverse effects MH - Cytokines/genetics/metabolism MH - Tumor Necrosis Factor-alpha/metabolism MH - Anti-Inflammatory Agents/adverse effects MH - Immunoglobulin E/adverse effects MH - RNA, Messenger/adverse effects PMC - PMC10272903 OTO - NOTNLM OT - HaCaT OT - amarogentin OT - atopic dermatitis-like mice OT - cytokines COIS- The authors declare that they have no conflicts of interest. Qian Zhang is an editorial board member of AMEM and a coauthor of this article. To minimize bias, she was excluded from all editorial decision making related to the acceptance of this article for publication. EDAT- 2022/09/23 06:00 MHDA- 2023/06/19 13:08 PMCR- 2022/09/21 CRDT- 2022/09/22 01:53 PHST- 2022/03/24 00:00 [received] PHST- 2022/06/02 00:00 [accepted] PHST- 2023/06/19 13:08 [medline] PHST- 2022/09/23 06:00 [pubmed] PHST- 2022/09/22 01:53 [entrez] PHST- 2022/09/21 00:00 [pmc-release] AID - AME212260 [pii] AID - 10.1002/ame2.12260 [doi] PST - ppublish SO - Animal Model Exp Med. 2023 Jun;6(3):255-265. doi: 10.1002/ame2.12260. Epub 2022 Sep 21.