Abstract
Background: Dracocephalum kotschyi is traditionally used for its anti-inflammatory effects. We aimed to investigate the effects of ethyl acetate extract of D. kotschyi on the expression of key inflammatory mediators and main signaling molecules involved in the regulation of inflammation.
Methods: Lipopolysaccharide (LPS)-stimulated J774.1 mouse macrophages were cultured in the presence of the plant extract and examined by the real time-PCR for gene expressions of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2. Cytokine levels and phosphorylated forms of stressactivated protein kinases/c-Jun N-terminal kinase (SAPK/JNK), signal transducer and activator of transcription (STAT)-3, p38, IκB-α and nuclear factor (NF)-κB p65 were determined using ELISA.
Results: The extract significantly reduced the expression of key mediators of inflammation. iNOS expression level decreased from 138±8.5 fold in LPS-only treated cells to 6.5±2.6 fold after treatment with 25 µg/ml of the extract (p<0.001). Similarly, COX-2 expression decreased from 632 ±98.8 fold in control to 124 ±24.6 fold (p<0.01). Treatment of cells with the extract significantly reduced IL-1β and TNF-α cytokines at both gene and protein expression levels. The extract at 25 µg/ml caused significant decreases in phospho- SAPK/JNK and phospho-STAT3 levels in macrophages (p<0.01). Proteins of phospho-p38, NFκB-p65 and phospho-NF-κB p65 had a reduced level in treated cells (p<0.05). No significant change in phospho-IκB level was observed.
Conclusion: These findings suggested that D. kotschyi with inhibition of NF-κB, SAPK/JNK, STAT-3 and p-38 might have reduced the expression levels of key inflammatory mediators and thus possibly have potential beneficial impact on inflammatory diseases.
Keywords: Anti-inflammatory, cytokines, Dracocephalum kotschyi, macrophages, transcription factors.
Graphical Abstract
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry
Title:Investigation of Dracocephalum kotschyi Plant Extract on the Effective Inflammatory Transcription Factors and Mediators in Activated Macrophages
Volume: 17 Issue: 1
Author(s): Kurosh Kalantar, Nasser Gholijani, Nashmin Mousaei, Malihe Yazdani and Zahra Amirghofran*
Affiliation:
- Department of Immunology, Medical School, Shiraz University of Medical Sciences, Shiraz,Iran
Keywords: Anti-inflammatory, cytokines, Dracocephalum kotschyi, macrophages, transcription factors.
Abstract: Background: Dracocephalum kotschyi is traditionally used for its anti-inflammatory effects. We aimed to investigate the effects of ethyl acetate extract of D. kotschyi on the expression of key inflammatory mediators and main signaling molecules involved in the regulation of inflammation.
Methods: Lipopolysaccharide (LPS)-stimulated J774.1 mouse macrophages were cultured in the presence of the plant extract and examined by the real time-PCR for gene expressions of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2. Cytokine levels and phosphorylated forms of stressactivated protein kinases/c-Jun N-terminal kinase (SAPK/JNK), signal transducer and activator of transcription (STAT)-3, p38, IκB-α and nuclear factor (NF)-κB p65 were determined using ELISA.
Results: The extract significantly reduced the expression of key mediators of inflammation. iNOS expression level decreased from 138±8.5 fold in LPS-only treated cells to 6.5±2.6 fold after treatment with 25 µg/ml of the extract (p<0.001). Similarly, COX-2 expression decreased from 632 ±98.8 fold in control to 124 ±24.6 fold (p<0.01). Treatment of cells with the extract significantly reduced IL-1β and TNF-α cytokines at both gene and protein expression levels. The extract at 25 µg/ml caused significant decreases in phospho- SAPK/JNK and phospho-STAT3 levels in macrophages (p<0.01). Proteins of phospho-p38, NFκB-p65 and phospho-NF-κB p65 had a reduced level in treated cells (p<0.05). No significant change in phospho-IκB level was observed.
Conclusion: These findings suggested that D. kotschyi with inhibition of NF-κB, SAPK/JNK, STAT-3 and p-38 might have reduced the expression levels of key inflammatory mediators and thus possibly have potential beneficial impact on inflammatory diseases.
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Kalantar Kurosh , Gholijani Nasser , Mousaei Nashmin , Yazdani Malihe and Amirghofran Zahra *, Investigation of Dracocephalum kotschyi Plant Extract on the Effective Inflammatory Transcription Factors and Mediators in Activated Macrophages, Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry 2018; 17 (1) . https://dx.doi.org/10.2174/1871523017666180608081656
DOI https://dx.doi.org/10.2174/1871523017666180608081656 |
Print ISSN 1871-5230 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-614X |

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