PMID- 30149753 OWN - NLM STAT- MEDLINE DCOM- 20181218 LR - 20181218 IS - 1793-6853 (Electronic) IS - 0192-415X (Linking) VI - 46 IP - 6 DP - 2018 TI - Ethanol Extract of Lilium Bulbs Plays an Anti-Inflammatory Role by Targeting the IKK[Formula: see text]/[Formula: see text]-Mediated NF-[Formula: see text]B Pathway in Macrophages. PG - 1281-1296 LID - 10.1142/S0192415X18500672 [doi] AB - Lilium bulbs have long been used as Chinese traditional medicines to alleviate the symptoms of various human inflammatory diseases. However, mechanisms of Lilium bulb-mediated anti-inflammatory activity and the bioactive components in Lilium bulbs remain unknown. In the present study, the anti-inflammatory activity of Lilium bulbs and the underlying mechanism of action were investigated in macrophages using Lilium bulb ethanol extracts (Lb-EE). In a dose-dependent manner, Lb-EE inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and bone marrow-derived macrophages (BMDMs) without causing significant cytotoxicity. Lb-EE also down-regulated mRNA expression of inflammatory genes in LPS-stimulated RAW264.7 cells, which included inducuble nitric oxide synthase (iNOS), cyclooxygenase-2 (COX2), and tumor necrosis factor-[Formula: see text] (TNF-[Formula: see text]). Furthermore, Lb-EE markedly restored LPS-induced morphological changes in RAW264.7 cells to a normal morphology. HPLC analysis identified quercetin, luteolin, and kaempferol as bioactive components contained in Lb-EE. Mechanistic studies in LPS-stimulated RAW264.7 cells revealed that Lb-EE suppressed MyD88- and TRIF-induced NF-[Formula: see text]B transcriptional activation and the nuclear translocation of NF-[Formula: see text]B transcription factors. Moreover, Lb-EE inhibited IKK[Formula: see text]/[Formula: see text]-induced activation of the NF-[Formula: see text]B signaling pathway and IKK inhibition significantly reduced NO production in LPS-stimulated RAW264.7 cells. Taken together, these results suggest that Lb-EE plays an anti-inflammatory role by targeting IKK[Formula: see text]/[Formula: see text]-mediated activation of the NF-[Formula: see text]B signaling pathway during macrophage-mediated inflammatory responses. FAU - Han, Sang Yun AU - Han SY AD - * Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea. FAU - Yi, Young-Su AU - Yi YS AD - dagger Department of Pharmaceutical Engineering, Cheongju University, Cheongju 28503, Republic of Korea. FAU - Jeong, Seong-Gu AU - Jeong SG AD - * Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea. FAU - Hong, Yo Han AU - Hong YH AD - * Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea. FAU - Choi, Kang Jun AU - Choi KJ AD - double dagger Horticultural Research Division, Gangwondo Provincial Agricultural Research and Extension Services, Chuncheon 24226, Republic of Korea. FAU - Hossain, Mohammad Amjad AU - Hossain MA AD - section sign Department of Veterinary Physiology, College of Medicine, Chonbuk National University, Iksan 54596, Republic of Korea. FAU - Hwang, Hyunsik AU - Hwang H AD - * Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea. FAU - Rho, Ho Sik AU - Rho HS AD - paragraph sign Department of Chemical Engineering, College of Engineering, Suwon University, Suwon 18323, Republic of Korea. FAU - Lee, Jongsung AU - Lee J AD - * Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea. FAU - Kim, Jong-Hoon AU - Kim JH AD - section sign Department of Veterinary Physiology, College of Medicine, Chonbuk National University, Iksan 54596, Republic of Korea. FAU - Cho, Jae Youl AU - Cho JY AD - * Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea. LA - eng PT - Journal Article DEP - 20180827 PL - Singapore TA - Am J Chin Med JT - The American journal of Chinese medicine JID - 7901431 RN - 0 (Anti-Inflammatory Agents) RN - 0 (NF-kappa B) RN - 0 (Plant Extracts) RN - 31C4KY9ESH (Nitric Oxide) RN - 3K9958V90M (Ethanol) RN - EC 2.7.11.10 (I-kappa B Kinase) SB - IM MH - Animals MH - *Anti-Inflammatory Agents MH - Cell Survival/drug effects MH - Ethanol MH - HEK293 Cells MH - Humans MH - I-kappa B Kinase/*metabolism MH - Lilium/*chemistry MH - Macrophages/*immunology/*metabolism MH - Mice MH - NF-kappa B/*metabolism MH - Nitric Oxide/metabolism MH - Plant Extracts/isolation & purification/*pharmacology MH - RAW 264.7 Cells MH - Signal Transduction/*drug effects/*genetics OTO - NOTNLM OT - Anti-Inflammatory OT - IKK/ OT - Lilium Bulbs OT - Macrophage OT - NF-B EDAT- 2018/08/29 06:00 MHDA- 2018/12/19 06:00 CRDT- 2018/08/29 06:00 PHST- 2018/08/29 06:00 [pubmed] PHST- 2018/12/19 06:00 [medline] PHST- 2018/08/29 06:00 [entrez] AID - 10.1142/S0192415X18500672 [doi] PST - ppublish SO - Am J Chin Med. 2018;46(6):1281-1296. doi: 10.1142/S0192415X18500672. Epub 2018 Aug 27.