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Excessive nitric oxide (NO) production by macrophages has been involved in inflammatory diseases. Seven polyphenols ( 1 - 7 ) were isolated from Broussonetia kazinoki (B. kazinoki) and investigated as potential inhibitors of NO overproduction in lipopolysaccharide (LPS)-activated RAW 264.7 cells. Among them, four prenylated polyphenols ( 2 - 4 and 6 ) with a catechol moiety efficiently suppressed the LPS-induced high level of NO with IC 50 values of less than 6 µM. The compounds 2 - 4 and 6 also attenuated protein and mRNA levels of inducible nitric oxide synthase (iNOS). Moreover, they suppressed the nuclear factor κB (NF-κB) activity by inhibiting the degradation of inhibitory-κB-α (I-κB-α) and the translocation of NF-κB into the nucleus in LPS-activated macrophages. Taken together, these findings suggest that polyphenols from B. kazinoki might be beneficial for treatment of inflammatory diseases., Competing Interests: The authors declare no conflict of interest.

Series of carbamate and thiocarbamate derivatives were designed and synthesized and their inhibitory activities of NO production in lipopolysaccharide-activated macrophages were evaluated. Several thoicarbamate derivatives revealed promising inhibitory activity. The structure-activity relationship study of these compounds is also reported. Among these compounds, compound 12b was the most potent with 6.5 μM of IC(50). They inhibited NO production through the suppression of iNOS protein and mRNA expression and nuclear translocation of p65., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The overproduction of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) is known to be responsible for vasodilation and hypotension observed in septic shock and inflammation. Inhibitors of iNOS, thus, may be useful candidates for the treatment of inflammatory diseases accompanied by overproduction of NO. In the course of screening oriental anti-inflammatory herbs for the inhibitory activity of NO synthesis, a crude methanolic extract of Curcuma zedoaria exhibited significant activity. The activity-guided fractionation and repetitive chromatographic procedures with the EtOAc soluble fraction allowed us to isolate three active compounds. They were identified as 1,7-bis (4-hydroxyphenyl)-1,4,6-heptatrien-3-one (1), procurcumenol (2) and epiprocurcumenol (3) by spectral data analyses. Their concentrations for the 50% inhibition of NO production (IC50) in lipopolysaccharide (LPS)-activated macrophages were 8, 75, 77 microM, respectively. Compound 1 showed the most potent inhibitory activity for NO production in LPS-activated macrophages, while the epimeric isomers, compound 2 and 3 showed weak and similar potency. Inhibition of NO synthesis by compound 1 was very weak when activated macrophages were treated with 1 after iNOS induction. In the immunoblot analysis, compound 1 suppressed the expression of iNOS in a dose-dependent manner. In summary, 1,7-bis (4-hydroxyphenyl)-1,4,6-heptatrien-3-one from Curcuma zedoaria inhibited NO production in LPS-activated macrophages through suppression of iNOS expression. These results imply that the traditional use of C. zedoaria rhizome as anti-inflammatory drug may be explained at least in part, by inhibition of NO production.

Four sesquiterpenoids were isolated from an ethyl acetate-soluble fraction of A. princeps ethanolic extract: seco-tanapartholide B (5-epi-seco-tanapartholide A) (1), 4-epi-seco-tanapartholide A (2), 11,13-dehydrodesacetylmatricarin (3) and desacetylmatricarin (4). Compounds 1 − 3 dose-dependently inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-activated macrophages. These compounds also decreased mRNA and protein expression levels of inducible NO synthase and cyclooxygenase-2 as well as mRNA levels of pro-inflammatory cytokines (interleukin-1β and tumour necrosis factor-α) in LPS-stimulated RAW 264.7 macrophages. Moreover, compound 3 effectively enhanced the expression of heme oxygenase-1 (HO-1) in macrophages in the presence or absence of LPS. Additionally, the exocyclic methylene of α-methylene-γ-lactone moiety of compound 3 was found to be essential for the activation of the NF erythroid 2-related factor 2 (Nrf2)/HO-1 pathway. Here, we firstly report the isolation of compounds 3 and 4 from A. princeps and the anti-inflammatory activity of compound 3 by up-regulation of Nrf2/HO-1 pathway. [ABSTRACT FROM AUTHOR]

The overproduction of nitric oxide (NO) and prostaglandin E2 (PGE2) by microglia may cause neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. From the activity-guided purification of Cullen corylifolium (L.) Medik. (syn. Psoralea corylifolia L.), three prenylated chalcones were identified: isobavachalcone (1), bavachromene (2), and kanzonol B (3). These prenylated chalcones showed concentration-dependent inhibitory effects on NO and PGE2 production in lipopolysaccharide (LPS)-activated microglia. Western blotting and RT-PCR analysis demonstrated that these prenylchalcones reduced the expression of protein and mRNA of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-activated microglia. Furthermore, three prenylated chalcones blocked the inhibitory-κBα (I-κBα) degradation and down-regulated nuclear factor κB (NF-κB) level of nucleus in LPS-stimulated BV-2 microglia. Therefore, these prenylated chalcones from Psoralea corylifolia may be beneficial for the treatment of neuro-inflammatory diseases by modulating iNOS and COX-2 expressions in activated microglial cells. [ABSTRACT FROM AUTHOR]

The ethyl acetate-soluble fraction from the ethanolic extract of Angelica keiskei showed potent inhibitory activity against the production of nitric oxide (NO) in lipopolysaccharide (LPS)-activated RAW 264.7 cells. We identified seven chalcones ( 1- 7) from EtOAc-soluble fractions through the activity-guided separation. Four active principles, identified as 4-hydroxyderrcine ( 1), xanthoangelol E ( 2), xanthokeismin A ( 4), and xanthoangelol B ( 5), inhibited the production of NO and the expression of proinflammatory cytokines, interleukin (IL)-1β and IL-6, in LPS-activated macrophages. Western blotting and reverse transcription-polymerase chain reaction analysis demonstrated that these chalcones attenuated protein and mRNA levels of inflammatory enzymes such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Moreover, these active compounds suppressed the degradation of inhibitory- κB α (I- κB α) and the translocation of nuclear factor κB (NF- κB) into nuclei of LPS-activated macrophages. These data demonstrate that four chalcones ( 1, 2, 4, and 5) from A. keiskei can suppress the LPS-induced production of NO and the expression of iNOS/COX-2 genes by inhibiting the degradation of I- κB α and nuclear translocation of NF- κB. Taken together, four chalcones from A. keiskei may have efficacy as anti-inflammatory agents. [ABSTRACT FROM AUTHOR]

Abstract: Carabrol, isolated from Carpesium macrocephalum, showed anti-inflammatory potential in LPS-induced RAW 264.7 murine macrophages. In present study, carabrol demonstrated the inhibitory activity on pro-inflammatory cytokines such as IL-1β, IL-6 and TNF-α. In addition, mRNA and protein levels of iNOS and COX-2 were reduced by carabrol. Molecular analysis revealed that these suppressive effects were correlated with the inactivation of p38 and JNK via inhibition of NF-κB activation. Immunoblotting showed that carabrol suppressed LPS-induced degradation of I-κBα and decreased nuclear translocation of p65. Taken together, these results suggest that carabrol can be a modulator of pro-inflammatory signal transduction pathway in RAW 264.7 cells. [Copyright &y& Elsevier]

In relation to anti-inflammatory agents from medicinal plants, we have isolated three compounds from Atractylodes macrocephala; 1, 2-[(2E)-3,7-dimethyl-2,6-octadienyl]-6-methyl-2, 5-cyclohexadiene-1, 4-dione; 2, 1-acetoxy-tetradeca-6E,12E-diene-8, 10-diyne-3-ol; 3, 1,3-diacetoxy-tetradeca-6E, 12E-diene-8, 10-diyne. Compounds 1–3 showed concentration-dependent inhibitory effects on production of nitric oxide (NO) and prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. Western blotting and RT-PCR analyses demonstrated that compounds 1–3 suppressed the protein and mRNA levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, compounds 1–3 inhibited transcriptional activity of nuclear factor-κB (NF-κB) and nuclear translocation of NF-κB in LPS-activated RAW 264.7 cells. The most active compound among them, compound 1, could reduce the mRNA levels of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and suppress the phosphorylation of MAPK including p38, JNK, and ERK1/2. Taken together, these results suggest that compounds 1–3 from A. macrocephala can be therapeutic candidates to treat inflammatory diseases. [ABSTRACT FROM AUTHOR]

Abstract: Three sesquiterpenoids, xanthatin (1), xanthinosin (2), and 4-oxo-bedfordia acid (3) were isolated from Xanthium strumarium as inhibitors of nitric oxide synthesis in activated microglia (IC50 values: 0.47, 11.2, 136.5μM, respectively). Compounds 1 and 2 suppressed the expression of iNOS and COX-2 and the activity of NF-κB through the inhibition of LPS-induced I-κB-α degradation in microglia. [Copyright &y& Elsevier]

Abstract: Ethonopharmacological relevance: Thuja orientalis (L) ENDL (Cupressaceae) is an evergreen arbor that is distributed throughout Northeast Asia. This plant has been used as a traditional medicine for the treatment of various inflammatory diseases such as dermatitis, gout and chronic tracheitis. Aim of the study: To isolate the active principles responsible for the anti-inflammatory activities of Thuja orientalis and to disclose their mechanism of action in lipopolysaccharide (LPS)-stimulated macrophages. Materials and methods: The methanolic leaves and stem extracts of the Thuja orientalis were successively fractionated into EtOAc, n-BuOH and the remaining aqueous fractions. The EtOAc soluble fraction, which exhibited significant inhibitory activity on LPS-induced nitric oxide (NO) production, was followed by successive activity-guided chromatography to yield seven diterpenoids. The anti-inflammatory properties of active constituents were evaluated by RT-PCR, Western blotting and reporter gene assay in cell culture system. Results: A new labdane diterpene, 15-nor-14-oxolabda-8(17),13(16)-dien-19-oic acid (1), and six known diterpenoids (2–7) were isolated from the EtOAc extracts of Thuja orientalis. The isolated compounds 1–7 were evaluated for the inhibitory activity of LPS-induced NO production in RAW264.7 macrophage cells. Compound 1 was the most potent among the isolated compounds for the inhibition of LPS-induced NO production (IC50 1: 3.56μM). Compound 1 reduced the production of pro-inflammatory mediators and suppressed the expression of the inflammatory enzymes of iNOS and COX-2. In addition, compound 1 attenuated the LPS-induced transcriptional activity of NF-κB by the inhibition of inhibitory-κBα degradation, and suppressed the activity of extracellular signal regulated kinase (ERK). Conclusions: This study demonstrates that a new labdane diterpene from Thuja orientalis inhibits the inflammatory responses by the suppression of NF-κB activity and ERK phosphorylation. This compound might be a valuable candidate for the development of anti-inflammatory drugs. [Copyright &y& Elsevier]

Abstract: The overproduction of nitric oxide (NO) and prostaglandin E2 (PGE2) causes neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease. Four lignans, (+)-eudesmin (1), (+)-magnolin (2), (+)-yangambin (3) and a new structure named as epimagnolin B (4) were isolated from Magnolia fargesii (Magnoliaceae) as the inhibitors of NO production in LPS-activated microglia. The most potent compound 4 inhibited the production of NO and PGE2 and the expression of respective enzyme iNOS and COX-2 through the suppression of I-κB-α degradation and nuclear translocation of p65 subunit of NF-κB. [Copyright &y& Elsevier]