PMID- 29401674 OWN - NLM STAT- MEDLINE DCOM- 20180807 LR - 20240314 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 19 IP - 2 DP - 2018 Feb 3 TI - Scandoside Exerts Anti-Inflammatory Effect Via Suppressing NF-kappaB and MAPK Signaling Pathways in LPS-Induced RAW 264.7 Macrophages. LID - 10.3390/ijms19020457 [doi] LID - 457 AB - The iridoids of Hedyotis diffusa Willd play an important role in the anti-inflammatory process, but the specific iridoid with anti-inflammatory effect and its mechanism has not be thoroughly studied. An iridoid compound named scandoside (SCA) was isolated from H. diffusa and its anti-inflammatory effect was investigated in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. Its anti-inflammatory mechanism was confirmed by in intro experiments and molecular docking analyses. As results, SCA significantly decreased the productions of nitric oxide (NO), prostaglandin E(2) (PGE(2)), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) and inhibited the levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-alpha and IL-6 messenger RNA (mRNA) expression in LPS-induced RAW 264.7 macrophages. SCA treatment suppressed the phosphorylation of inhibitor of nuclear transcription factor kappa-B alpaha (IkappaB-alpha), p38, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). The docking data suggested that SCA had great binding abilities to COX-2, iNOS and IkappaB. Taken together, the results indicated that the anti-inflammatory effect of SCA is due to inhibition of pro-inflammatory cytokines and mediators via suppressing the nuclear transcription factor kappa-B (NF-kappaB) and mitogen-activated protein kinase (MAPK) signaling pathways, which provided useful information for its application and development. FAU - He, Jingyu AU - He J AD - Bioengineering Research Centre, Guangzhou Institute of Advanced Technology, Chinese Academy of Sciences, Guangzhou 511458, China. jy.he@giat.ac.cn. FAU - Li, Jiafeng AU - Li J AD - Bioengineering Research Centre, Guangzhou Institute of Advanced Technology, Chinese Academy of Sciences, Guangzhou 511458, China. jiafengli2018@gmail.com. FAU - Liu, Han AU - Liu H AD - Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China. hanliuchn@outlook.com. FAU - Yang, Zichao AU - Yang Z AD - Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China. zcyangchn@163.com. FAU - Zhou, Fenghua AU - Zhou F AD - School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China. wendy515@fimmu.com. FAU - Wei, Ting AU - Wei T AD - Bioengineering Research Centre, Guangzhou Institute of Advanced Technology, Chinese Academy of Sciences, Guangzhou 511458, China. ting.wei@siat.ac.cn. FAU - Dong, Yaqian AU - Dong Y AD - Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China. yqdongchn@163.com. FAU - Xue, Hongjiao AU - Xue H AD - Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China. xuehongjiao@sina.com. FAU - Tang, Lan AU - Tang L AD - Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China. tl405@smu.edu.cn. FAU - Liu, Menghua AU - Liu M AD - Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China. liumenghua@smu.edu.cn. LA - eng PT - Journal Article DEP - 20180203 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Interleukin-6) RN - 0 (Iridoids) RN - 0 (Lipopolysaccharides) RN - 0 (NF-kappa B) RN - 0 (Plant Extracts) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (interleukin-6, mouse) RN - 31C4KY9ESH (Nitric Oxide) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) RN - EC 1.14.13.39 (Nos2 protein, mouse) RN - EC 1.14.99.- (Ptgs2 protein, mouse) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - EC 2.7.11.10 (I-kappa B Kinase) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (Mapk1 protein, mouse) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - K7Q1JQR04M (Dinoprostone) SB - IM MH - Animals MH - Anti-Inflammatory Agents/chemistry/isolation & purification/*pharmacology MH - Cell Survival/drug effects MH - Cyclooxygenase 2/chemistry/genetics/metabolism MH - Dinoprostone/antagonists & inhibitors/biosynthesis MH - Hedyotis/*chemistry MH - I-kappa B Kinase/antagonists & inhibitors/chemistry/genetics/metabolism MH - Interleukin-6/genetics/metabolism MH - Iridoids/chemistry/isolation & purification/*pharmacology MH - JNK Mitogen-Activated Protein Kinases/genetics/metabolism MH - Lipopolysaccharides/*antagonists & inhibitors/pharmacology MH - Mice MH - Mitogen-Activated Protein Kinase 1/genetics/metabolism MH - Mitogen-Activated Protein Kinase 3/genetics/metabolism MH - Molecular Docking Simulation MH - NF-kappa B/*antagonists & inhibitors/genetics/metabolism MH - Nitric Oxide/antagonists & inhibitors/biosynthesis MH - Nitric Oxide Synthase Type II/antagonists & inhibitors/chemistry/genetics/metabolism MH - Plant Extracts/chemistry MH - RAW 264.7 Cells MH - Tumor Necrosis Factor-alpha/genetics/metabolism MH - p38 Mitogen-Activated Protein Kinases/*antagonists & inhibitors/genetics/metabolism PMC - PMC5855679 OTO - NOTNLM OT - anti-inflammation OT - mitogen-activated protein kinase OT - nuclear transcription factor kappa-B alpaha OT - scandoside COIS- The authors declare no conflict of interest. EDAT- 2018/02/07 06:00 MHDA- 2018/08/08 06:00 PMCR- 2018/02/01 CRDT- 2018/02/07 06:00 PHST- 2018/01/07 00:00 [received] PHST- 2018/01/29 00:00 [revised] PHST- 2018/01/31 00:00 [accepted] PHST- 2018/02/07 06:00 [entrez] PHST- 2018/02/07 06:00 [pubmed] PHST- 2018/08/08 06:00 [medline] PHST- 2018/02/01 00:00 [pmc-release] AID - ijms19020457 [pii] AID - ijms-19-00457 [pii] AID - 10.3390/ijms19020457 [doi] PST - epublish SO - Int J Mol Sci. 2018 Feb 3;19(2):457. doi: 10.3390/ijms19020457.