Licocoumarone isolated from Glycyrrhiza uralensis selectively alters LPS-induced inflammatory responses in RAW 264.7 macrophages

Abstract

The effects of licocoumarone (LC) isolated from Glycyrrhiza uralensis were studied in LPS-stimulated RAW 264.7 macrophages. Our study demonstrated that LC dose-dependently attenuated LPS-induced NO production by down-regulating iNOS expression. Additionally, the treatment with LC inhibited LPS-induced expression of cytokines including IL-1β, IL-6 and IL-10, but not TNF-α, at both mRNA and protein levels. Similar suppressive effects of LC were observed on LPS-stimulated murine peritoneal macrophages as well. Furthermore, LC significantly reduced LPS-stimulated NF-κB activation by inhibition of IκBα degradation and p65 phosphorylation. The results from NF-κB-luc reporter gene assay further support the inhibitory effect of LC on NF-κB activation. Further studies showed that LC also interfered with the MAPKs and STAT3 signaling pathways, which are typical inflammatory signaling pathways triggered by LPS. Taken together, these results show that LC attenuates LPS-induced cytokine gene expression in RAW 264.7 macrophages through mechanisms that involve NF-κB, MAPKs and STAT3 signaling pathways, but the pattern of inhibition differs from that of a global immunosuppresant. Our study indicates that LC is a functional constituent of Glycyrrhiza uralensis with potential implications in infectious and immune-related diseases.

Anti-Inflammatory Activities of Compounds Isolated from the Rhizome of Anemarrhena asphodeloides

“…Accumulation of nitrite, a metabolite of NO in the culture media, was measured by Griess assay as previously reported [ 37 ]. Briefly, cells were stimulated with 100 ng/mL of LPS for 24 h in the presence of the test compounds (0–50 μM).…”

2′-O-Galloylhyperin Isolated From Pyrola incarnata Fisch. Attenuates LPS-Induced Inflammatory Response by Activation of SIRT1/Nrf2 and Inhibition of the NF-κB Pathways in Vitro and Vivo

“…It has been known that activation of MAPKs (ERK1/2, p38, and JNK) is involved in modulating the NF-κB-regulated gene activation ( Wu et al, 2017 ) As shown in Figure 2E , 2′- O -GH significantly suppressed the LPS-induced phosphorylation of ERK1/2, p38, and JNK in a concentration-dependent manner. Furthermore, pretreatment with MAPK inhibitors (U0126, SP600125, and SB203580) suppressed the production of NO (Supplementary Figure S1 ).…”

“…Inflammation is a complex processes triggered by foreign pathogens or tissue injury to eliminate harmful stimuli as well as to initiate the healing and repair process of the damaged tissue ( Laveti et al, 2013 ). LPS is a major constituent of the cell wall of Gram-negative bacteria, which activates macrophages and induces inflammatory mediators and cytokines ( Mo et al, 2014 ; Wu et al, 2017 ). Overwhelming secretion of pro-inflammatory cytokines causes severe tissue damage, multiple organ failure, or death ( Ozer et al, 2017 ).…”

“…However, excessive inflammation is also involved in many human diseases including arthritis, metabolic syndrome, cancer, and atherosclerosis ( Laveti et al, 2013 ). LPS, a complex glycolipid in the outer membrane of Gram-negative bacteria, can innate immune system, because it binds the CD14/TLR4/MD2 receptor complex in many cell types, especially in monocytes and macrophages, which modulates cytokine networks by producing pro-inflammatory cytokines such as TNF-α, IL-6, and pro-inflammatory mediators including nitric oxide (NO) ( Mo et al, 2014 ; Wu et al, 2017 ). In addition, LPS also stimulates the production of ROS via the activation of NADPH-oxidase in macrophages ( Menon et al, 2014 ).…”

Heterogeneous macrophages: Supersensors of exogenous inducing factors

“…Aloe vera extract can downregulate TNF‐α, IL‐1β and IL‐6 expression in macrophages in a mouse model of lipopolysaccharide (LPS)‐induced acute lung injury (ALI), thus potentially protecting LPS‐induced ALI . Other extracts used in traditional Chinese medicine, such as curcumin, emodin, berberine and grass coumarone, have similar effects. Most of the traditional Chinese medications that inhibit tumours have “promoting blood stasis, reducing swelling and dispersing” effects.…”