PMID- 37529040 OWN - NLM STAT- MEDLINE DCOM- 20230803 LR - 20230803 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 14 DP - 2023 TI - Dietary artemisinin boosts intestinal immunity and healthy in fat greenling (Hexagrammos otakii). PG - 1198902 LID - 10.3389/fimmu.2023.1198902 [doi] LID - 1198902 AB - INTRODUCTION: Artemisinin (ART) is very common as a diet additive due to its immunoregulatory activities. Nonetheless, the immunoregulatory mechanism of ART in marine fish remains unknown. This study comprehensively examined the effects and explored the potential mechanism of ART ameliorating intestinal immune disease (IID) in fat greenlings (Hexagrammos otakii). METHODS AND RESULTS: The targets of ART were screened using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Here, eight putative targets of ART were collected and identified with the Uniprot database, and 1419 IID-associated target proteins were filtered through the Drugbank, Genecards, OMIM, and PHARMGKB Databases. The results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways point out that ART may have immunoprotective effects by regulating cellular responses to stress, hypoxia, inflammation, and vascular endothelial growth factor stimulus through the hypoxia-inducible factor 1 (HIF-1) signaling pathway. The findings of molecular docking indicated that ART contains one active ingredient and three cross-targets, which showed a kind combination with hypoxia-inducible factor 1-alpha (HIF1-a), transcription factor p65 (RELA), and vascular endothelial growth factor A (VEGF-A), respectively. Furthermore, an ART feeding model was established to assess the ART's immunoprotect effect on the intestine of H.otakii in vivo. The D48 group showed smaller intestinal structural changes after being challenged by Edwardsiella tarda. The supplementation of ART to the diet improved total superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) and reduced the malondialdehyde (MDA) in intestine of H. otakii. The expression of transcription factor p65, HIF1-alpha, VEGF-A, cyclin D1, matrix metalloprotease 9 (MMP9), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) was decreased after dietary ART in the intestinal of H. otakii. DISCUSSION: The present results demonstrated that dietary ART improved antioxidants and immunity, optimized the intestinal structure, and increased resistance to E. tarda through the SOD2/nuclear-factor-kappa- B (NFkB)/HIF1-a/VEGF-A pathway in the intestinal tract of H.otakii. This study integrated pharmacological analysis and experimental validation and revealed the mechanism of ART on IID, which provides insight into the improvement of IID in H. otakii. CI - Copyright (c) 2023 Gu, Wang, Zhan, Wei, Shi, Cui, Peng, Han, Li, Chen, Xue and Wang. FAU - Gu, Yixin AU - Gu Y AD - Key Laboratory of Applied Biology and Aquaculture of Northern Fishes in Liaoning Province, Dalian Ocean University, Dalian, China. FAU - Wang, Wenjie AU - Wang W AD - Key Laboratory of Applied Biology and Aquaculture of Northern Fishes in Liaoning Province, Dalian Ocean University, Dalian, China. FAU - Zhan, Yu AU - Zhan Y AD - Key Laboratory of Applied Biology and Aquaculture of Northern Fishes in Liaoning Province, Dalian Ocean University, Dalian, China. FAU - Wei, Xiaoyan AU - Wei X AD - Key Laboratory of Applied Biology and Aquaculture of Northern Fishes in Liaoning Province, Dalian Ocean University, Dalian, China. FAU - Shi, Yanyan AU - Shi Y AD - Key Laboratory of Applied Biology and Aquaculture of Northern Fishes in Liaoning Province, Dalian Ocean University, Dalian, China. FAU - Cui, Dandan AU - Cui D AD - Key Laboratory of Applied Biology and Aquaculture of Northern Fishes in Liaoning Province, Dalian Ocean University, Dalian, China. FAU - Peng, Tingting AU - Peng T AD - Key Laboratory of Applied Biology and Aquaculture of Northern Fishes in Liaoning Province, Dalian Ocean University, Dalian, China. FAU - Han, Jian AU - Han J AD - Key Laboratory of Applied Biology and Aquaculture of Northern Fishes in Liaoning Province, Dalian Ocean University, Dalian, China. FAU - Li, Xuejie AU - Li X AD - Key Laboratory of Applied Biology and Aquaculture of Northern Fishes in Liaoning Province, Dalian Ocean University, Dalian, China. FAU - Chen, Yan AU - Chen Y AD - Key Laboratory of Applied Biology and Aquaculture of Northern Fishes in Liaoning Province, Dalian Ocean University, Dalian, China. FAU - Xue, Zhuang AU - Xue Z AD - Key Laboratory of Applied Biology and Aquaculture of Northern Fishes in Liaoning Province, Dalian Ocean University, Dalian, China. FAU - Wang, Wei AU - Wang W AD - Key Laboratory of Applied Biology and Aquaculture of Northern Fishes in Liaoning Province, Dalian Ocean University, Dalian, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230717 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Vascular Endothelial Growth Factor A) RN - 0 (Transcription Factor RelA) RN - 9RMU91N5K2 (artemisinin) RN - 0 (Artemisinins) SB - IM MH - Animals MH - Vascular Endothelial Growth Factor A MH - Transcription Factor RelA MH - Molecular Docking Simulation MH - Dietary Supplements MH - Diet MH - Intestines MH - *Perciformes MH - *Artemisinins/pharmacology PMC - PMC10388541 OTO - NOTNLM OT - Hexagrammos otakii OT - artemisinin OT - intestinal immune disease OT - molecular docking OT - network pharmacology COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2023/08/02 06:42 MHDA- 2023/08/03 06:43 PMCR- 2023/01/01 CRDT- 2023/08/02 03:49 PHST- 2023/04/02 00:00 [received] PHST- 2023/06/27 00:00 [accepted] PHST- 2023/08/03 06:43 [medline] PHST- 2023/08/02 06:42 [pubmed] PHST- 2023/08/02 03:49 [entrez] PHST- 2023/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2023.1198902 [doi] PST - epublish SO - Front Immunol. 2023 Jul 17;14:1198902. doi: 10.3389/fimmu.2023.1198902. eCollection 2023.