Amelioration of an LPS-induced inflammatory response using a methanolic extract of Lagerstroemia ovalifolia to suppress the activation of NF-κB in RAW264.7 macrophages

Park, Ji Won; Kwon, OK; Yuniato, Prasetyawan; Marwoto, Bambang; Lee, Dong Kun; Oh, Sei Ryang; Kim, Jae Hong; Ahn, Kyung Seop

doi:10.3892/ijmm.2016.2646

Cited by 17 publications

(22 citation statements)

References 31 publications

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“…For herbal extracts, several mechanisms of interference with the production or activity of eicosanoids have been described including the regulation of enzyme expression [8][9][10] and enzyme activity [11], but also by influencing the expression of eicosanoid receptors [8,12].…”

Section: Introductionmentioning

confidence: 99%

A tiered approach to investigate the mechanism of anti-inflammatory activity of an herbal medicinal product containing a fixed combination of thyme herb and primula root extracts

et al. 2018

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Background: The herbal medicinal product Bronchipret® TP film-coated tablets contains a fixed combination of thyme and primula dry extracts (BRO) and has long and successfully been used for the treatment of acute bronchitis. However, the underlying pharmacological mechanisms of action have not been determined so far. We report a tiered approach applying in vivo and in vitro studies to investigate the pharmacodynamic activity and underlying mechanisms of action, and to identify possible active ingredients contributing to the product's pharmacodynamic activity. Results: In an LPS-induced rat model of bronchoalveolitis oral administration of BRO effectively ameliorated the influx of leukocytes into the lung. This was accompanied by reduced levels of leukotriene (LT) B 4 , cysteinyl-LTs (cysLT), and prostaglandin (PG) E 2 . We also found that BRO potently reduced the production of LTB 4 in vitro in rat whole blood stimulated with the Ca 2+ -ionophore A23187 whereas the effect on PGE 2 was much less pronounced. The transferability of these findings to human cells was assessed by measuring the effects of BRO on A23187stimulated human monocytes and neutrophils. BRO and thyme extract were potent inhibitors of LTB 4 and cysLT production. We further investigated the effects of BRO, thyme extract as well as single compounds of thyme extract on enzymatic activity of 5-lipoxygenase (5-LO). 5-LO activity was potently reduced by BRO and thyme extract. Of the single ingredients, thymoquinone and rosmarinic acid showed most potent inhibitory activity against 5-LO, with lower potency for thymol and carvacrol.Conclusion: BRO attenuates inflammation-induced leukotriene formation in vivo and affects leukotriene biosynthesis in vitro via 5-LO inhibition. This inhibitory activity appears to be primarily related to the thyme extract component. However, none of the single ingredients tested seems to fully account for the activity of thyme extract alone. Rather, the interaction of different compounds seems to be required for its overall inhibitory effect on leukotriene production.

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Section: Introductionmentioning

confidence: 99%

A tiered approach to investigate the mechanism of anti-inflammatory activity of an herbal medicinal product containing a fixed combination of thyme herb and primula root extracts

et al. 2018

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“…In general, mitogen and differentiation signals are able to activate the ERK while stress stimuli activate p38 and JNK [ 61 ]. Many studies have illustrated that the up-regulation of TNF-α, IL-1β, and IL-6 is diminished by phytochemicals through the inhibition of the activation of ERK, JNK, and p38 [ 6 , 62 ]. In this paper, MHP and linarin down-regulated the phosphorylation levels of ERK, JNK, and p38.…”

Section: Discussionmentioning

confidence: 99%

“…Macrophages are phagocytic white blood cells that play an important role in innate immune inflammatory responses. Activated macrophages secrete various cytokines such as tumor necrosis factor-α (TNF-α), interlenkin-1β (IL-1β), interlenkin-6 (IL-6), and other inflammatory cytokines [ 5 ], which show pleiotropic effects via activating adaptive immune responses and worsening inflammatory responses [ 6 ]. The nuclear factor kappa-B (NF-κB) signaling pathway is involved in regulating diverse gene expression during inflammatory responses [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

The Phenolic Fraction of Mentha haplocalyx and Its Constituent Linarin Ameliorate Inflammatory Response through Inactivation of NF-κB and MAPKs in Lipopolysaccharide-Induced RAW264.7 Cells

et al. 2017

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Mentha haplocalyx has been widely used for its flavoring and medicinal properties and as a traditional Chinese medicine with its anti-inflammation properties. The present study was designed to investigate the anti-inflammatory effects and potential molecular mechanisms of the phenolic fraction of M. haplocalyx (MHP) and its constituent linarin in lipopolysaccharide (LPS)-induced RAW264.7 cells. The high-performance liquid chromatography coupled with linear ion trap-orbitrap mass spectrometry (HPLC-LTQ-Orbitrap MS) was used to analyze the chemical composition of MHP. Using the enzyme-linked immunosorbent assay (ELISA) and quantitative realtime polymerase chain reaction (qRT-PCR), the expression of pro-inflammatory meditators and cytokines was measured at the transcriptional and translational levels. Western blot analysis was used to further investigate changes in the nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK), and Akt signaling pathways. Fourteen phenolic constituents were identified from MHP based on the data of the mass spectrometry (MS)/MS analysis. MHP and linarin decreased the production of NO, tumor necrosis factor-α (TNF-α), interlenkin-1β (IL-1β), and IL-6. The messenger ribonucleic acid (mRNA) expression levels of inducible NO synthase (iNOS), TNF-α, IL-1β, and IL-6 were also suppressed by MHP and linarin. Further investigation showed that MHP and linarin down-regulated LPS-induced phosphorylation content of NF-κB p65, inhibitor kappa B α (IκBα), extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38. However, MHP and linarin showed no inhibitory effect on the phosphorylated Akt. These results suggested that MHP and linarin exerted a potent inhibitory effect on pro-inflammatory meditator and cytokines production via the inactivation of NF-κB and MAPKs, and they may serve as potential modulatory agents for the prevention and treatment of inflammatory diseases.

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“…These subunits block IκB-α in its normal state, but upon stimulation by the inflammatory response, IκB-α undergoes phosphorylation and is degraded, while NF-κB is activated (18). LPS induces the activation of NF-κB, which then stimulates the expression of pro-inflammatory cytokines, including IL-6 and TNF-α, as well as chemokines (19). Therefore, the present study confirmed that CSME suppressed LPS-induced inflammatory mediators and cytokines, as well as phosphorylation of IκB-α and p65, in RAW264.7 cells.…”

Section: Discussionmentioning

confidence: 99%

Anti-inflammatory effects of a methanolic extract of Castanea seguinii Dode in LPS-induced RAW264.7 macrophage cells

et al. 2017

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Castanea extracts are known to have antioxidant properties and are used as a traditional medicine in China and Asia. However, the biological activity of Castanea seguinii Dode has remained to be fully elucidated. The present study investigated the anti-inflammatory effects of a Castanea seguinii Dode methanolic extract (CSME) on lipopolysaccharide-induced RAW264.7 macrophage cells. CSME inhibited the production of nitric oxide (NO) and the expression of inducible NO synthase. It also suppressed the production of the pro-inflammatory cytokines inteleukin-6 and tumor necrosis factor-α, as well as chemokine monocyte chemoattractant protein 1. In addition, CSME inhibited nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling, while also downregulating transcription factor activator protein-1. Furthermore, CSME increased heme oxygenase 1 through the upregulation of NF (erythroid-derived 2)-like-2 (Nrf-2), which directly or indirectly affects inflammation. It also increased the phosphorylation of 5'-adenosine monophosphate-activated protein kinase (AMPK). In conclusion, CSME was demonstrated to exert its anti-inflammatory activities through the inhibition of the NF-κB and the MAPK signaling pathways, as well as the activation of Nrf-2 and AMPK. These results indicated that CSME may be a promising for development as a commercial anti-inflammatory medicine.

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Amelioration of an LPS-induced inflammatory response using a methanolic extract of Lagerstroemia ovalifolia to suppress the activation of NF-κB in RAW264.7 macrophages

Cited by 17 publications

References 31 publications

A tiered approach to investigate the mechanism of anti-inflammatory activity of an herbal medicinal product containing a fixed combination of thyme herb and primula root extracts

A tiered approach to investigate the mechanism of anti-inflammatory activity of an herbal medicinal product containing a fixed combination of thyme herb and primula root extracts

The Phenolic Fraction of Mentha haplocalyx and Its Constituent Linarin Ameliorate Inflammatory Response through Inactivation of NF-κB and MAPKs in Lipopolysaccharide-Induced RAW264.7 Cells

Anti-inflammatory effects of a methanolic extract of Castanea seguinii Dode in LPS-induced RAW264.7 macrophage cells

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