• Asian-Australasian Journal of Animal Sciences
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• v.33 no.7
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• pp.1167-1179
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• 2020

Objective: This study was conducted to fathom the underlying mechanisms of nutrition intervention and redox sensitive transcription factors regulated by Antrodia cinnamomea fermented product (FAC) dietary supplementation in broiler chickens. Methods: Four hundreds d-old broilers (41±0.5 g/bird) assigned to 5 groups were examined after consuming control diet, or control diet replaced with 5% wheat bran (WB), 10% WB, 5% FAC, and 10% FAC. Liver mRNA expression of antioxidant, inflammatory and lipid metabolism pathways were analyzed. Prostaglandin E2 (PGE₂) concentration in each group were tested in the chicken peripheral blood mononuclear cells (cPBMCs) of 35-d old broilers to represent the stress level of the chickens. Furthermore, these cells were stimulated with 2,2'-Azobis(2-amidinopropane) dihydrochloride (AAPH) and lipopolysaccharide (LPS) to evaluate the cell stress tolerance by measuring cell viability and oxidative species. Results: Heme oxygenase-1, glutathione S-transferase, glutamate-cysteine ligase, catalytic subunit, and superoxide dismutase, and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) that regulates the above antioxidant genes were all up-regulated significantly in FAC groups. Reactive oxygen species modulator protein 1 and NADPH oxygenase 1 were both rather down-regulated in 10% FAC group as comparison with two WB groups. Despite expressing higher level than control group, birds receiving diet containing FAC had significantly lower expression level in nuclear factor-kappa B (NF-κB) and other genes (inducible nitric oxide synthase, tumor necrosis factor-α, interleukin-1β, nucleotide-binding domain, leucine-richcontaining family, pyrin domain-containing-3, and cyclooxygenase 2) involving in inflammatory pathways. Additionally, except for 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase that showed relatively higher in both groups, the WB, lipoprotein lipase, Acetyl-CoA carboxylase, fatty acid synthase, fatty acid binding protein, fatty acid desaturase 2 and peroxisome proliferator-activated receptor alpha genes were expressed at higher levels in 10% FAC group. In support of above results, promoted Nrf2 and inhibited NF-κB nuclear translocation in chicken liver were found in FAC containing groups. H₂O₂ and NO levels induced by LPS and AAPH in cPBMCs were compromised in FAC containing diet. In 35-d-old birds, PGE₂ production in cPBMCs was also suppressed by the FAC diet. Conclusion: FAC may promote Nrf2 antioxidant pathway and positively regulate lipid metabolism, both are potential inhibitor of NF-κB inflammatory pathway.

• Journal of Ginseng Research
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• v.36 no.2
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• pp.161-168
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• 2012

The abnormal maturation and ossification of articular chondrocytes play a central role in the pathogenesis of osteoarthritis (OA). Inhibiting the enzymatic degradation of the extracellular matrix and maintaining the cellular phenotype are two of the major goals of interest in managing OA. Ginseng is frequently taken orally, as a crude substance, as a traditional medicine in Asian countries. Ginsenoside $Rb_1$, a major component of ginseng that contains an aglycone with a dammarane skeleton, has been reported to exhibit various biological activities, including anti-inflammatory and anti-tumor effects. However, a chondroprotective effect of ginsenoside $Rb_1$ related to OA has not yet been reported. The purpose of this study was to demonstrate the chondroprotective effect of ginsenoside $Rb_1$ on the regulation of pro-inflammatory factors and chondrogenic genes. Cultured rat articular chondrocytes were treated with 100 ${\mu}M$ ginsenoside $Rb_1$ and/or 500 ${\mu}M$ hydrogen peroxide ($H_2O_2$) and assessed for viability, reactive oxygen species production, nitric oxide (NO) release, and chondrogenic gene expression. Ginsenoside $Rb_1$ treatment resulted in reductions in the levels of pro-inflammatory cytokine and NO in $H_2O_2$-treated chondrocytes. The expression levels of chondrogenic genes, such as type II collagen and SOX9, were increased in the presence of ginsenoside $Rb_1$, whereas the expression levels of inflammatory genes related to chondrocytes, such as MMP1 and MMP13, were reduced by approximately 50%. These results suggest that ginsenoside $Rb_1$ has potential for use as a therapeutic agent in OA patients.

• Journal of Life Science
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• v.29 no.7
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• pp.809-816
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• 2019

The ubiquitous plant metabolite p-coumaric acid (p-CA) has antioxidant and anti-inflammatory properties, but its anti-cancer activity has not been established in gastric cancer cell lines. In this study, we investigated the effects of p-CA on the proliferation and transcriptome profile of SNU16 gastric cancer cells. Treatment with p-CA induced apoptosis of the SNU-16 cells by regulating the expression of pro-apoptotic and anti-apoptotic proteins, such as Bcl-2, poly (ADP-ribose) polymerase (PARP), Bax, procaspase-3, and cleaved-caspase-3. The genes differentially expressed in response to p-CA treatment of the SNU-16 cells were identified by RNA sequencing analysis. Genes regulated by p-CA were involved mainly in the inflammatory response, apoptotic processes, cell cycle, and immune response. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that the phosphatidylinositol-3-kinase-Akt and cancer signaling pathways were altered by p-CA. Protein-protein interaction (PPI) network analysis also revealed that p-CA treatment was correlated with differential expression of genes associated with the inflammatory response and cancer. Collectively, these results suggest that p-CA has potential utility in gastric cancer prevention.

• The Journal of Internal Korean Medicine
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• v.25 no.1
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• pp.46-58
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• 2004

Objectives : This study was designed to investigate the effects of Injinchunggan-tang(Yinchenqinggan-tang) on the expression of inflammatory cytokine genes and proteins in kupffer cells. Materials and Methods : The mRNA expression level and protein secretion level were measured using quantitative RT-PCR and ELISA assay respectively in Injinchunggan-tang-treated and untreated kupffer cells after exposed to ethanol, acetaldehyde and lipopolysaccharide. Results : Injinchunggan-tang(Yinchenqinggan-tang) reduced mRNA expression level and protein secretion level of $TNF-{\alpha},\;TGF-{\beta}1,\;IL-1{\beta},\;IL-6,\;IL-8$ that are induced by ethanol, acetaldehyde and lipopolysaccharide in kupffer cells and that mediate inflammation and fibrosis of liver. Conclusion : The result indicates that Injinchunggan-tang (Yinchenqinggan-tang) blocks alcohol-induced liver injury and protects liver by reducing production of inflammatory cytokines.

• The Journal of Internal Korean Medicine
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• v.34 no.4
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• pp.339-348
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• 2013

Objectives : Danguieumja is a traditional medicinal prescription to treat skin disease. It was commonly used for the treatment of itching, chronic urticaria and atopic dermatitis in Korea by the addition or omission of several herbs. This study investigated the anti-inflammatory potential of Gagam-Danguieumja (GDE) water extract. Methods : We examined the effects of GDE on the lipopolysaccharide (LPS)-induced production of nitric oxide (NO) in a murine macrophage cell line, RAW 264.7 cells. Results : GDE inhibited production of NO in a dose dependent manner and also decreased the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2). As a possible molecular mechanism of anti-inflammatory effect increased phosphorylation of mitogen-activating protein kinases (MAPK) by LPS were blocked by GDE treatment. Conclusions : These results suggest that GDE has an anti-inflammatory therapeutic potential through the inhibition of MAPK phosphorylation, thereby decreasing the expression of pro-inflammatory genes.

• Molecules and Cells
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• v.26 no.1
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• pp.48-52
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• 2008

We here demonstrate an anti-inflammatory action of raloxifene, a selective estrogen receptor modulator, in lipopolysaccharide (LPS)-induced murine macrophage RAW264.7 cells. Treatment with raloxifene at micromolar concentrations suppressed the production of nitric oxide (NO) by down-regulating expression of the inducible nitric oxide synthase (iNOS) gene in LPS-activated cells. The decreased expression of iNOS and subsequent reduction of NO were due to inhibition of nuclear translocation of transcription factor NF-${\kappa}B$. These effects were significantly inhibited by exposure to the phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor, LY294002, or by expression of a dominant negative mutant of PI 3-kinase. In addition, pretreatment with raloxifene reduced LPS-induced Akt phosphorylation as well as NF-${\kappa}B$ DNA binding activity and NF-${\kappa}B$-dependent reporter gene activity. Thus our findings indicate that raloxifene exerts its anti-inflammatory action in LPS-stimulated macrophages by blocking the PI 3-kinase-Akt-NF-${\kappa}B$ signaling cascade, and eventually reduces expression of pro-inflammatory genes such as iNOS.

• Molecules and Cells
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• v.37 no.6
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• pp.441-448
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• 2014

Inflammasomes are specialized signaling platforms critical for the regulation of innate immune and inflammatory responses. Various NLR family members (i.e., NLRP1, NLRP3, and IPAF) as well as the PYHIN family member AIM2 can form inflammasome complexes. These multiprotein complexes activate inflammatory caspases (i.e., caspase-1) which in turn catalyze the maturation of select pro-inflammatory cytokines, including interleukin (IL)-$1{\beta}$ and IL-18. Activation of the NLRP3 inflammasome typically requires two initiating signals. Toll-like receptor (TLR) and NOD-like receptor (NLR) agonists activate the transcription of pro-inflammatory cytokine genes through an NF-${\kappa}B$-dependent priming signal. Following exposure to extracellular ATP, stimulation of the P2X purinoreceptor-7 ($P2X_7R$), which results in $K^+$ efflux, is required as a second signal for NLRP3 inflammasome formation. Alternative models for NLRP3 activation involve lysosomal destabilization and phagocytic NADPH oxidase and /or mitochondria-dependent reactive oxygen species (ROS) production. In this review we examine regulatory mechanisms that activate the NLRP3 inflammasome pathway. Furthermore, we discuss the potential roles of NLRP3 in metabolic and cognitive diseases, including obesity, type 2 diabetes mellitus, Alzheimer's disease, and major depressive disorder. Novel therapeutics involving inflammasome activation may result in possible clinical applications in the near future.

• Food Science of Animal Resources
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• v.35 no.5
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• pp.604-610
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• 2015

We investigated the synergic anti-inflammatory activity of Gleditsia sinensis Lam. (GS) extract and Lactobacillus brevis KY21 both in vitro and in vivo. Western blot analysis and immunostaining showed that AKT phosphorylation that increased by the exposure of LPS were significantly decreased by the presence of either GS extract or L. brevis KY21. In addition, p65 intracellular transport was critically inhibited by GS extract and L. brevis KY21. We further studied these effects using an in vivo dextran sulfate sodium (DSS)-induced mouse model. Body weight, food intake, and clinical scores were dramatically decreased after treatment with DSS, whereas these effects were palliated by the addition of GS extract and L. brevis KY21. Importantly, transcription of genes encoding pro-inflammatory cytokines including IL-1β, TNF-α, and IFN-γ in mesenteric lymph nodes (MLN) and the spleen were increased by DSS treatment, whereas they were inhibited by the presence of GS extract and L. brevis KY21.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.5
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• pp.413-420
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• 2015

Dexmedetomidine is a sedative and analgesic agent that exerts its effects by selectively agonizing ${\alpha}2$ adrenoceptor. Histamine is a pathophysiological amine that activates G protein-coupled receptors, to induce $Ca^{2+}$ release and subsequent mediate or progress inflammation. Dexmedetomidine has been reported to exert inhibitory effect on inflammation both in vitro and in vivo studies. However, it is unclear that dexmedetomidine modulates histamine-induced signaling and pro-inflammatory cytokine expression. This study was carried out to assess how dexmedetomidine modulates histamine-induced $Ca^{2+}$ signaling and regulates the expression of pro-inflammatory cytokine genes encoding interleukin (IL)-6 and -8. To elucidate the regulatory role of dexmedetomidine on histamine signaling, HeLa cells and human salivary gland cells which are endogenously expressed histamine 1 receptor were used. Dexmedetomidine itself did not trigger $Ca^{2+}$ peak or increase in the presence or absence of external $Ca^{2+}$. When cells were stimulated with histamine after pretreatment with various concentrations of dexmedetomidine, we observed inhibited histamine-induced $[Ca^{2+}]_i$ signal in both cell types. Histamine stimulated IL-6 mRNA expression not IL-8 mRNA within 2 hrs, however this effect was attenuated by dexmedetomidine. Collectively, these findings suggest that dexmedetomidine modulates histamine-induced $Ca^{2+}$ signaling and IL-6 expression and will be useful for understanding the antagonistic properties of dexmedetomidine on histamine-induced signaling beyond its sedative effect.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.6
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• pp.513-520
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• 2023

Cornuside is a secoiridoid glucoside compound extracted from the fruits of Cornus officinalis. Cornuside has immunomodulatory and anti-inflammatory properties; however, its potential therapeutic effects on diabetic nephropathy (DN) have not been completely explored. In this study, we established an in vitro model of DN through treating mesangial cells (MMCs) with glucose. MMCs were then treated with different concentrations of cornuside (0, 5, 10, and 30 μM). Cell viability was determined using cell counting kit-8 and 5-ethynyl-2'-deoxyuridine assays. Levels of proinflammatory cytokines, including interleukin (IL)-6, tumor necrosis factor-α, and IL-1β were examined using enzyme-linked immunosorbent assay. Reverse transcription quantitative real-time polymerase chain reaction and Western blotting were performed to detect the expression of AKT and nuclear factor-kappa B (NF-κB)-associated genes. We found that cornuside treatment significantly reduced glucose-induced increase in MMC viability and expression of pro-inflammatory cytokines. Moreover, cornuside inhibited glucose-induced phosphorylation of AKT and NF-κB inhibitor alpha, decreased the expression of proliferating cell nuclear antigen and cyclin D1, and increased the expression of p21. Our study indicates that the anti-inflammatory properties of cornuside in DN are due to AKT and NF-κB inactivation in MMCs.