Suffrutines A and B Inhibit the Expression of Inflammatory Mediators in LPS-Induced RAW264.7 Cells by Suppressing the NF-κB Signaling Pathway

Abstract Flueggea suffruticosa is a traditional Chinese medicine that has been commonly used for the treatment of inflammatory ailments, including rheumatism and lumbago. Suffrutines A and suffrutines B are a pair of novel E,E and Z,E isomeric indolizidine alkaloids isolated from the roots of F. suffruticosa. However, their anti-inflammatory activity has not been reported thus far. The aim of this study was to investigate the inhibitory effect of inflammatory mediators and possible mechanisms of suffrutines A and B in lipopolysaccharide-induced RAW264.7 cells. Results showed that suffrutines A and B could remarkably inhibit the production of nitric oxide, prostaglandin E2, interleukin-6, inducible nitric oxide synthase, and cyclooxygenase-2 in lipopolysaccharide-induced RAW264.7 cells. Further evaluation demonstrated that compared with suffrutines A, suffrutines B could more significantly inhibit the phosphorylation of IKKα/β, the degradation of IκBα, and the nuclear translocation of the p65 and p52 subunits in the canonical and non-canonical nuclear factor-κB pathways. Therefore, suffrutines B exhibited more potent inhibitory activity on inflammatory mediators than suffrutines A.

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Anti-Inflammatory Activity of Three Triterpene from Hippophae rhamnoides L. in Lipopolysaccharide-Stimulated RAW264.7 Cells

International Journal of Molecular Sciences ◽

10.3390/ijms222112009 ◽

2021 ◽

Vol 22 (21) ◽

pp. 12009

Author(s):

Yu Han ◽

Chen Yuan ◽

Xiaowei Zhou ◽

Yingjie Han ◽

Yanhao He ◽

...

Keyword(s):

Nitric Oxide ◽

Nuclear Translocation ◽

Raw264.7 Cells ◽

Asiatic Acid ◽

Inflammatory Factor ◽

Maslinic Acid ◽

Anti Inflammatory ◽

Oxide Synthase ◽

Inducible Nitric Oxide

Oleanolic acid (OA), asiatic acid (AA), and maslinic acid (MA) are ubiquitous isomeric triterpene phytochemicals with many pharmacological effects. To improve their application value, we used lipopolysaccharide (LPS) to induce RAW264.7 cells and studied the differences in the anti-inflammatory effects of the triterpenes according to their structural differences. MTT, Griess, and immunofluorescence assays, ELISA, flow cytometry, and Western blotting, were performed. The release of LPS-induced pro-inflammatory mediators, such as nitric oxide (NO), inducible nitric oxide synthase (iNOS), and interleukin (IL-6), was significantly inhibited by OA, AA, and MA at the same concentration, and AA and MA promoted the production of anti-inflammatory factor IL-10. OA, AA, and MA inhibited LPS-induced NF-κB nuclear translocation in RAW264.7 cells. OA and AA inhibited the phosphorylation of ERK1/2, P38, and JNK1/2 in LPS-stimulated RAW264.7 cells. Moreover, OA increased LPS-induced Nrf2 expression and decreased Keap1 expression in RAW264.7 cells. OA, AA, and MA inhibited LPS-stimulated intracellular reactive oxygen species (ROS) production and alleviated mitochondrial membrane potential depletion. Overall, our data suggested that OA, AA, and MA exhibited significant anti-inflammatory effects in vitro. In particular, OA and AA take effects through the MAPKs, NF-κB, and Nrf2 signaling pathways.

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Herbacetin inhibits inducible nitric oxide synthase via JNK and nuclear factor-κB in LPS-stimulated RAW264.7 cells

European Journal of Pharmacology ◽

10.1016/j.ejphar.2015.08.032 ◽

2015 ◽

Vol 765 ◽

pp. 115-123 ◽

Cited By ~ 22

Author(s):

Liang Li ◽

Mahesh Sapkota ◽

Se-woong Kim ◽

Yunjo Soh

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Inducible Nitric Oxide Synthase ◽

Nuclear Factor Κb ◽

Raw264.7 Cells ◽

Nuclear Factor ◽

Oxide Synthase ◽

Inducible Nitric Oxide

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Suppressive effects of sulfated polysaccharide ascophyllan isolated from Ascophyllum nodosum on the production of NO and ROS in LPS-stimulated RAW264.7 cells

Bioscience Biotechnology and Biochemistry ◽

10.1093/bbb/zbaa115 ◽

2020 ◽

Vol 85 (4) ◽

pp. 882-889

Author(s):

Yan Liang ◽

Shijiao Zha ◽

Masanobu Tentaku ◽

Takasi Okimura ◽

Zedong Jiang ◽

...

Keyword(s):

Nitric Oxide ◽

Ascophyllum Nodosum ◽

Sulfated Polysaccharide ◽

Intracellular Reactive Oxygen Species ◽

Raw264.7 Cells ◽

Dependent Manner ◽

Oxygen Species ◽

Oxide Synthase ◽

Dose Dependent ◽

Inducible Nitric Oxide

ABSTRACT In this study, we found that a sulfated polysaccharide isolated from the brown alga Ascophyllum nodosum, ascophyllan, showed suppressive effects on stimulated RAW264.7 cells. Ascophyllan significantly inhibited expression of inducible nitric oxide synthase mRNA and excessive production of nitric oxide (NO) in lipopolysaccharide (LPS)-stimulated RAW264.7 cells in a dose-dependent manner without affecting the viability of RAW264.7 cells. Ascophyllan also reduced the elevated level of intracellular reactive oxygen species (ROS) in LPS-stimulated RAW264.7 cells. Furthermore, preincubation with ascophyllan resulted in concentration-dependent decrease in ROS production in phorbol 12-myristate-13-acetate-stimulated RAW264.7 cells. Our results suggest that ascophyllan can exhibit anti-inflammatory effects on stimulated macrophages mainly through the attenuation of NO and ROS productions.

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Activation of Nuclear Factor κB and Induction of Inducible Nitric Oxide Synthase by Ureaplasma urealyticumin Macrophages

Infection and Immunity ◽

10.1128/iai.68.12.7087-7093.2000 ◽

2000 ◽

Vol 68 (12) ◽

pp. 7087-7093 ◽

Cited By ~ 28

Author(s):

Y.-H. Li ◽

Z.-Q. Yan ◽

J. Skov Jensen ◽

K. Tullus ◽

A. Brauner

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Inducible Nitric Oxide Synthase ◽

Alveolar Macrophages ◽

Nuclear Factor Κb ◽

Inos Expression ◽

Dependent Manner ◽

Nuclear Factor ◽

Oxide Synthase ◽

Inducible Nitric Oxide

ABSTRACT Chronic lung disease (CLD) of prematurity is an inflammatory disease with a multifactorial etiology. The importance ofUreaplasma urealyticum in the development of CLD is debated, and steroids produce some improvement in neonates with this disease. In the present study, the capability of U. urealyticum to stimulate rat alveolar macrophages to produce nitric oxide (NO), express inducible nitric oxide synthase (iNOS), and activate nuclear factor κB (NF-κB) in vitro was characterized. The effect of NO on the growth of U. urealyticum was also investigated. In addition, the impact of dexamethasone and budesonide on these processes was examined. We found that U. urealyticum antigen (≥4 × 107 color-changing units/ml) stimulated alveolar macrophages to produce NO in a dose- and time-dependent manner (P < 0.05). This effect was further enhanced by gamma interferon (100 IU/ml; P < 0.05) but was attenuated by budesonide and dexamethasone (10−4 to 10−6 M) (P < 0.05). The mRNA and protein levels of iNOS were also induced in response to U. urealyticum and inhibited by steroids.U. urealyticum antigen triggered NF-κB activation, a possible mechanism for the induced iNOS expression, which also was inhibited by steroids. NO induced by U. urealyticum caused a sixfold reduction of its own growth after infection for 10 h. Our findings imply that U. urealyticum may be an important factor in the development of CLD. The host defense response againstU. urealyticum infection may also be influenced by NO. The down-regulatory effect of steroids on NF-κB activation, iNOS expression, and NO production might partly explain the beneficial effect of steroids in neonates with CLD.

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