Abstract
Corydalis bungeana Turcz. is an anti-inflammatory medicinal herb used widely in traditional Chinese medicine for upper respiratory tract infections. It is demonstrated that corynoline is its active anti-inflammatory component. The nuclear factor-erythroid-2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway and the mitogen-activated protein kinase (MAPK) pathway play important roles in the regulation of inflammation. In this study, we investigated the potential anti-inflammatory mechanism of corynoline through modulation of Nfr2 and MAPKs. Lipopolysaccharide (LPS)-activated RAW264.7 cells were used to explore modulatory role of NO production and the activation of signaling proteins and transcription factors using nitrite assay, Western bloting and qPCR. Treatment with corynoline reduced production of nitric oxide (NO) and the protein and mRNA levels of inducible nitric oxide (iNOS) and cyclooxygenase-2 (COX-2) Treatment also significantly increased the expression of Nrf2, quinone oxidoreductase 1 (NQO1) and hemeoxygenase-1 (HO-1) at the mRNA and protein levels, which demonstrated that corynoline may protect cells from inflammation through the Nrf2/ARE pathway In addition, corynoline suppressed the expression of inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), at the mRNA and protein levels. Furthermore, molecular data revealed that corynoline inhibited lipopolysaccharide-stimulated phosphorylation of c-jun NH2-terminal kinase (JNK) and p38. Taken together, these results suggest that corynoline reduces the levels of pro-inflammatory mediators, such as iNOS, COX-2, TNF-α and IL-1β, by suppressing extracellular signal-regulated kinase 1/2 (ERK) and p38 phosphorylation in RAW264.7 cells, which is regulated by the Nrf2/ARE pathway. These findings reveal part of the molecular basis for the anti-inflammatory properties of corynoline.
Highlights
Inflammation is a physiological defense response of the body to tissue damage caused by microbial pathogen infections, chemical irritation and/or wounding [1]
Because corynoline showed the strongest induction of antioxidant response element (ARE)-luciferase activity at 24 h (Figure 2B), we evaluated the expression of nuclear factor-erythroid-2-related factor 2 (Nrf2) and its target genes NQO-1 and HO-1 at the mRNA and protein we evaluated the expression of Nrf2 and its target genes NQO-1 and HO-1 at the mRNA and protein levels
NQO-1 in proteins (p < 0.05)ofcompared the and LPS-treated group. These results indicate the and NQO-1 proteins. These results indicate that the anti-inflammatory effects of corynoline on the Nrf2/ARE pathway may be mediated by its ability to anti-inflammatory effects of corynoline on the pathway may be mediated by its ability to up-regulate the levels of Nrf2, HO-1 and NQO1
Summary
Inflammation is a physiological defense response of the body to tissue damage caused by microbial pathogen infections, chemical irritation and/or wounding [1]. There are two types of inflammatory responses: acute inflammation and chronic inflammation. An acute inflammatory the response is usually beneficial because it is a part of the defense response to irritation, injury and infection, and is characterized by pain, redness, swelling and sometimes loss of function. Failure to resolve acute inflammation may lead to chronic inflammation and various diseases, including cancer [2]. Chronic inflammation has been identified in various steps of tumorigenesis, including cellular transformation, promotion, survival, proliferation, invasion, angiogenesis and metastasis [3,4]. Several studies have reported increased levels of these cytokines in some types of cancer, thereby providing strong support for their possible roles in cancer progression [5,6]
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