title: Inhibitory effects of flavonoids extracted from Nepalese propolis on the LPS signaling pathway.
abstract: Flavonoids, particularly those derived from plants, harbor biological effects such as anti-inflammation and the inhibition of cancer progression. In the present study, we investigated the effects of 10 kinds of flavonoids isolated from Nepalese propolis on the LPS signaling pathway in order to clarify their anti-inflammatory activities. Five types of flavonoids: isoliquiritigenin, chrysin, 3',4'-dihydroxy-4-methoxydalbergione, 4-methoxydalbergion, and cearoin, markedly inhibited inflammatory responses including LPS-induced NO production by suppressing the expression of iNOS mRNA and LPS-induced mRNA expression of TNFα and CCL2. Their inhibitory effects on LPS-induced inflammatory responses correlated with the intensities of these flavonoids to suppress the LPS-induced activation of nuclear factor κB (NF-κB), an essential transcription factor for the mRNA expression of iNOS, TNFα, and CCL2. Among these flavonoids, 3',4'-dihydroxy-4-methoxydalbergione and 4-methoxydalbergion markedly inhibited the LPS-induced activation of IKK, thereby abrogating the degradation of IκBα and nuclear localization of NF-κB. On the other hand, isoliquiritigenin, chrysin, and cearoin failed to inhibit these signaling steps, but suppressed the transcriptional activity of NF-κB, which caused their anti-inflammatory effects. The results of the present study revealed that these five kinds of flavonoids are the components of Nepalese propolis that exhibit anti-inflammatory activities with a different regulatory mechanism for the activation of NF-κB.
authors: Graduate School of Pharmaceutical Sciences, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan. Electronic address: tago-mg@pha.keio.ac.jp.
authors: Megumi
authors: M
authors: Funakoshi-Tago
authors: Graduate School of Pharmaceutical Sciences, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
authors: Kentaro
authors: K
authors: Ohsawa
authors: Graduate School of Pharmaceutical Sciences, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
authors: Toshiyuki
authors: T
authors: Ishikawa
authors: Graduate School of Pharmaceutical Sciences, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
authors: Fumika
authors: F
authors: Nakamura
authors: Graduate School of Pharmaceutical Sciences, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
authors: Fumihito
authors: F
authors: Ueda
authors: Graduate School of Pharmaceutical Sciences, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
authors: Yuji
authors: Y
authors: Narukawa
authors: Graduate School of Pharmaceutical Sciences, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
authors: Fumiyuki
authors: F
authors: Kiuchi
authors: Graduate School of Pharmaceutical Sciences, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
authors: Hiroomi
authors: H
authors: Tamura
authors: Department of Biochemistry, Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
authors: Kenji
authors: K
authors: Tago
authors: Graduate School of Pharmaceutical Sciences, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
authors: Tadashi
authors: T
authors: Kasahara
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy*; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D011429:Propolis / Q000276:immunology*; D000067996:RAW 264.7 Cells; D015398:Signal Transduction / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D018932:Chemokine CCL2; D005419:Flavonoids; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D011429:Propolis; D052247:Nitric Oxide Synthase Type II
keywords: Anti-inflammatory activity; Flavonoid; IKK; LPS; NF-κB; Propolis