PMID- 37076464 OWN - NLM STAT- MEDLINE DCOM- 20230831 LR - 20230831 IS - 1875-5402 (Electronic) IS - 1386-2073 (Linking) VI - 26 IP - 14 DP - 2023 TI - Nomilin Attenuates Lipopolysaccharide-Induced Inflammatory Response by Binding with Myeloid Differentiation Protein-2. PG - 2469-2475 LID - 10.2174/1386207326666230418112827 [doi] AB - BACKGROUND: Nomilin shows anti-inflammatory activity by inhibiting the activation of the Toll-like receptor 4 (TLR 4)/NF-kappaB pathway. However, the key target of the anti-inflammatory activity of nomilin has not been elaborated and needs further exploration. OBJECTIVE: This study aimed to assess the drug potential of nomilin and its ability to target myeloid differentiation protein 2 (MD-2) as a mechanism underlying the anti-inflammatory activity of nomilin on the lipopolysaccharide (LPS)-TLR4/MD-2-NF-kappaB signaling pathways. METHODS: The methods of ForteBio and molecular docking were used to investigate the internation between MD-2 and nomilin. 3-(4,5)-Dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide experiment was performed to test the effect of nomilin on cell viability. Enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and Western blot experiments were carried out to assess the anti-inflammatory activity and possible mechanism of nomilin in vitro. RESULTS: The results indicated that nomilin exhibited binding affinity with MD-2. Nomilin significantly reduced the release and expression of NO, IL-6, TNF-alpha, and IL-1beta induced by LPS in vitro. It inhibited the expression of LPS-TLR4/MD-2-NF-kappaB signaling pathway proteins, such as TLR4, Myd88, P65, P-P65, and iNOS. CONCLUSION: Our results suggested that nomilin had therapeutic potential and was bound to MD-2. Nomilin exhibited anti-inflammatory activity by binding to the key protein MD-2 and inhibiting the LPS-TLR4/MD-2-NF-kappaB signaling pathway. CI - Copyright(c) Bentham Science Publishers; For any queries, please email at epub@benthamscience.net. FAU - Chen, Yuting AU - Chen Y AD - College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, China. FAU - Guo, Song AU - Guo S AD - Department of Computer Application, Shenyang Sport University, Shenyang, 110102, China. FAU - Chen, Guirong AU - Chen G AD - College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, China. AD - Department of Pharmacy, 967th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army, Dalian, Liaoning, China. FAU - Liu, Chang AU - Liu C AD - College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, China. FAU - Zhang, Mingbo AU - Zhang M AD - College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, China. FAU - Wang, Xiaobo AU - Wang X AD - Department of Pharmacy, 967th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army, Dalian, Liaoning, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United Arab Emirates TA - Comb Chem High Throughput Screen JT - Combinatorial chemistry & high throughput screening JID - 9810948 RN - 0 (NF-kappa B) RN - 0 (Lipopolysaccharides) RN - 0 (Toll-Like Receptor 4) RN - DRM0753K4T (nomilin) RN - 0 (Anti-Inflammatory Agents) SB - IM MH - *NF-kappa B/metabolism MH - *Lipopolysaccharides/pharmacology MH - Toll-Like Receptor 4/metabolism MH - Molecular Docking Simulation MH - Anti-Inflammatory Agents/pharmacology MH - Cell Differentiation OTO - NOTNLM OT - Anti-inflammatory activity OT - ELISA OT - LPS-TLR4/MD-2-NF-kappaB signaling pathway OT - lipopolysaccharide OT - myeloid differentiation protein 2 OT - nomilin EDAT- 2023/04/20 00:41 MHDA- 2023/08/31 06:42 CRDT- 2023/04/19 23:13 PHST- 2022/07/21 00:00 [received] PHST- 2023/02/12 00:00 [revised] PHST- 2023/03/03 00:00 [accepted] PHST- 2023/08/31 06:42 [medline] PHST- 2023/04/20 00:41 [pubmed] PHST- 2023/04/19 23:13 [entrez] AID - CCHTS-EPUB-131082 [pii] AID - 10.2174/1386207326666230418112827 [doi] PST - ppublish SO - Comb Chem High Throughput Screen. 2023;26(14):2469-2475. doi: 10.2174/1386207326666230418112827.