PMID- 36081795 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220912 IS - 1664-302X (Print) IS - 1664-302X (Electronic) IS - 1664-302X (Linking) VI - 13 DP - 2022 TI - Trichodimerol inhibits inflammation through suppression of the nuclear transcription factor-kappaB/NOD-like receptor thermal protein domain associated protein 3 signaling pathway. PG - 999996 LID - 10.3389/fmicb.2022.999996 [doi] LID - 999996 AB - Excessive inflammation causes chronic diseases and tissue damage. Although there has been drug treatment, its side effects are relatively large. Searching for effective anti-inflammatory drugs from natural products has become the focus of attention. First isolated from Trichoderma longibraciatum, trichodimerol is a natural product with TNF inhibition. In this study, lipopolysaccharide (LPS)-induced RAW264.7 macrophages were used as a model to investigate the anti-inflammatory activity of trichodimerol. The results of nitric oxide (NO) detection, enzyme-linked immunosorbent assay (ELISA), and reactive oxygen species (ROS) showed that trichodimerol could reduce the production of NO, ROS, and the proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha. Western blotting results showed that trichodimerol could inhibit the production of inflammatory mediators such as cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) and the protein expression of nuclear transcription factor-kappaB (NF-kappaB), p-IKK, p-IkappaB, Toll-like receptor 4 (TLR4), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), cysteinyl aspartate specific proteinase (Caspase)-1, and ASC, which indicated that trichodimerol may inhibit inflammation through the NF-kappaB and NLRP3 pathways. At the same time, molecular docking showed that trichodimerol can directly combine with the TLR4-MD2 complex. Hence, trichodimerol inhibits inflammation by obstructing the interaction between LPS and the TLR4-MD2 heterodimer and suppressing the downstream NF-kappaB and NLRP3 pathways. CI - Copyright (c) 2022 Huo, Lei, Guo, Hu, Kuang, Liu, Peng, Dai, Wang, Gu, Guo and Deng. FAU - Huo, Xue-Yan AU - Huo XY AD - State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China. FAU - Lei, Li-Rong AU - Lei LR AD - State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China. FAU - Guo, Wen-Xiu AU - Guo WX AD - State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China. FAU - Hu, Yun-Jie AU - Hu YJ AD - State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China. FAU - Kuang, Qi-Xuan AU - Kuang QX AD - State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China. FAU - Liu, Meng-Dan AU - Liu MD AD - State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China. FAU - Peng, Wan AU - Peng W AD - Institute of Rare Diseases, West China Hospital of Sichuan University, Chengdu, China. FAU - Dai, Yi-Fei AU - Dai YF AD - Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China. FAU - Wang, Dong AU - Wang D AD - State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China. FAU - Gu, Yu-Cheng AU - Gu YC AD - Syngenta Jealott's Hill International Research Centre, Berkshire, United Kingdom. FAU - Guo, Da-Le AU - Guo DL AD - State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China. FAU - Deng, Yun AU - Deng Y AD - State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China. LA - eng PT - Journal Article DEP - 20220823 PL - Switzerland TA - Front Microbiol JT - Frontiers in microbiology JID - 101548977 PMC - PMC9445571 OTO - NOTNLM OT - NF-kappaB OT - NLRP3 OT - inflammation OT - molecular docking OT - trichodimerol 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- 2022/09/10 06:00 MHDA- 2022/09/10 06:01 PMCR- 2022/08/23 CRDT- 2022/09/09 02:12 PHST- 2022/07/21 00:00 [received] PHST- 2022/08/01 00:00 [accepted] PHST- 2022/09/09 02:12 [entrez] PHST- 2022/09/10 06:00 [pubmed] PHST- 2022/09/10 06:01 [medline] PHST- 2022/08/23 00:00 [pmc-release] AID - 10.3389/fmicb.2022.999996 [doi] PST - epublish SO - Front Microbiol. 2022 Aug 23;13:999996. doi: 10.3389/fmicb.2022.999996. eCollection 2022.