Abstract
BackgroundCanscora lucidissima (Levl. & Vaniot) Hand.-Mazz. (C. lucidissima), mainly distributed in southern China, has been shown to be effective in the treatment of inflammatory diseases. However, the underlying mechanism of its anti-inflammatory effect is not fully understood.MethodsIn this study, we investigated the anti-inflammatory mechanism of ethanol extract of C. lucidissima (Cl-EE) in lipopolysaccharide (LPS)-induced inflammatory models. ELISA, real-time PCR, Western blot and luciferase reporter assay were used for the experiments in vitro, and ICR mouse endotoxemia model was used for in vivo test.ResultsOur data showed that Cl-EE reduced the production of NO by down-regulating the mRNA and protein expression of inducible nitric oxide synthase (iNOS) in LPS-activated RAW 264.7 cells. Meanwhile, it potently decreased other proinflammatory mediators, such as TNF-α, IL-6, MCP-1 and IL-1β at the transcriptional and translational levels. Further study indicated that Cl-EE did not affect NF-κB signaling pathway but significantly suppressed the phosphorylation of ERK1/2, rather than JNK or p38. In a LPS-induced endotoxemia mouse model, a single intraperitoneal injection of Cl-EE (75–300 mg/kg) could lower circulatory TNF-α, IL-6 and MCP-1 levels.ConclusionsCollectively, our results indicated that Cl-EE suppressed the phosphorylation level of ERK1/2 thus reducing the transcription and translation of inflammatory genes, thereby exerted anti-inflammatory activity. This study reveals the anti-inflammatory mechanism of C. lucidissima and may provide an effective treatment option for a variety of inflammatory diseases.
Highlights
Canscora lucidissima (Levl. & Vaniot) Hand.-Mazz. (C. lucidissima), mainly distributed in southern China, has been shown to be effective in the treatment of inflammatory diseases
The present study aims to evaluate the effects of the ethanol extract of C. lucidissima (Cl-EE) on inflammation in LPS-activated macrophages and the corresponding in vivo model and further explore the underlying mechanism
Ethanol extract of C. lucidissima (Cl-EE) suppresses LPS-induced inducible nitric oxide synthase (iNOS) mRNA and protein expression As NO is generated by iNOS in the activated macrophages, we investigated whether the inhibitory effect of Cl-EE on supernatant NO was attributed to the down-regulation of iNOS activity or expression in LPSstimulated RAW264.7 cells
Summary
Canscora lucidissima (Levl. & Vaniot) Hand.-Mazz. (C. lucidissima), mainly distributed in southern China, has been shown to be effective in the treatment of inflammatory diseases. (C. lucidissima), mainly distributed in southern China, has been shown to be effective in the treatment of inflammatory diseases. Macrophages play a crucial role in killing pathogen microbes and resulting in activating. The IκB kinase (IKK) complex, consisting of IKKα, IKKβ and the regulatory subunit NEMO, plays a vital role in myeloid cells. It is well-documented that IKKβ, rather than IKKα [5, 6], can phosphorylate IκBα and lead. IKK complex activation causes the polyubiquitination and degradation of NF-κB1 p105 [7], which releases TPL-2 from NF-κB1 p105 inhibition and allows TPL-2 to phosphorylate its substrate MEK [8]. Effective antiinflammatory agents are indispensable to suppress these excessive cytokines [9]
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