• Biomedical Science Letters
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• v.25 no.1
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• pp.92-98
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• 2019

Metformin is a drug used for the treatment of diabetes and is associated with anti-inflammatory reaction, but the underlying mechanism is unclear. In this study, we investigated the effect of metformin on the inflammatory response in BV-2 microglial cells induced by lipopolysaccharide (LPS) and S100 calcium-binding protein A8 (S100A8). The results revealed that metformin significantly attenuated several inflammatory responses in BV-2 microglial cells, including the secretion of pro-inflammatory cytokines, such as tumor necrosis factor-${\alpha}$ and interleukin (IL)-6, involved in the activation of Beclin-1, a crucial regulator of autophagy. In addition, metformin inhibited the LPS-induced phosphorylation of ERK. Metformin also suppressed the activation of NOD-like receptor pyrin domain containing 3 inflammasomes composed of NLRP3, caspase-1, and apoptosis-associated speck like protein containing a caspase recruitment domain, which are involved in the innate immune response. Notably, metformin decreased the secretion of S100A8-induced IL-6 production. These findings suggest that metformin alleviates the neuroinflammatory response via autophagy activation.

• Food Science of Animal Resources
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• v.32 no.4
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• pp.434-440
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• 2012

It has been suggested that probiotics could be useful for the prevention of symptomatic relapse in patients with inflammatory bowel disease (IBD). Interleukin (IL)-8 has been well recognized as one of the pro-inflammatory cytokines that could trigger inflammation and epithelial barrier dysfunction. In this study, the anti-inflammatory effects of probiotics were investigated using a human epithelial cell line (HT-29). Probiotics from infant feces and kimchi were tested for their cytotoxicity and effects on adhesion to epithelial cells. The present results show that seven strains could form 70 % adhesion on HT-29. The probiotics used in this study did not affect HT-29 cell viability. To screen anti-inflammatory lactic acid bacteria, HT-29 cells were pretreated with live and heat-killed probiotics, and lipopolysaccharide (LPS) ($1{\mu}g/mL$) was then added to stimulate the cells. The cell culture supernatant was then used to measure IL-8 secretion by ELISA, and the cell pellet was used to determine IL-8 and toll-like receptor (TLR-4) mRNA expression levels by RT-PCR. Some probiotics (KJP421, KDK411, SRK414, E4191, KY21, and KY210) exhibited anti-inflammatory effects through the repression of IL-8 secretion from HT-29 cells. In particular, Lactobacillus salivarius E4191, originating from Egyptian infant feces, not only decreased IL-8 mRNA expression, but also decreased TLR-4 expression. These results indicate that Lactobacillus salivarius E4191 may have a protective effect in intestinal epithelial cells.

• Korean Journal of Agricultural Science
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• v.46 no.3
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• pp.579-589
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• 2019

Due to the ban on the use of antibiotics, interest has been increasing for the development of therapeutic agents to treat various diseases using natural resources. Osthole, a natural coumarin compound used in traditional Chinese medicines, exerts an anti-inflammatory effect, but its effects in cows remain unknown. In this study, the effect of osthole on lipopolysaccharide (LPS)- or concanavalin-A (Con-A)- stimulated peripheral blood mononuclear cells (PBMCs) was assessed. Jugular venous blood was collected from Korean calves, and PBMCs were isolated. They were then used to study the immune response of PBMCs to treatment with osthole and LPS or Con-A for 72 h by measuring inflammatory cytokines including tumor necrosis factor-${\alpha}$ ($TNF-{\alpha}$) and interferon-${\gamma}$ ($IFN-{\gamma}$). Osthole significantly inhibited the mRNA secretion of $TNF-{\alpha}$ and $IFN-{\gamma}$ in a dose-dependent manner. Therefore, osthole inhibited LPS- or Con-A- induced $TNF-{\alpha}$ and Con-A-induced $IFN-{\gamma}$ production significantly in dose-dependent manner. These results clearly suggest that osthole inhibited the LPS- or Con-A- stimulated upregulation of pro-inflammatory cytokines in a dose-dependent manner, without causing obvious cytotoxic effects. Osthole could also protect cows from LPS- or Con-A- induced endotoxin shock, possibly by inhibiting the production of pro-inflammatory cytokines, which suggests that osthole might be a novel therapeutic agent for the prevention of inflammatory diseases.

• Nutrition Research and Practice
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• v.17 no.1
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• pp.164-173
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• 2023

BACKGROUND/OBJECTIVES: Hyperglycemia is a major cause of diabetes and diabetesrelated diseases. Sodium butyrate (NaB) is a short-chain fatty acid derivative that produces dietary fiber by anaerobic bacterial fermentation in the large intestine and occurs in foods, such as Parmesan cheese and butter. Butyrate has been shown to prevent obesity, improve insulin sensitivity, and ameliorate dyslipidemia in diet-induced obese mice. Therefore, this study examined the effects and mechanism of NaB on the secretion of inflammatory cytokines induced by high glucose (HG) in THP-1 cells. MATERIALS/METHODS: THP-1 cells were used as an in vitro model for HG-induced inflammation. The cells were cultured under normal glycemic or hyperglycemic conditions with or without NaB (0-25 μM). Western blotting and quantitative polymerase chain reaction were used to evaluate the protein and mRNA levels of nuclear factor-κB (NF-κB), interleukin-6, tumor necrosis factor-α, acetylated p65, acetyl CREB-binding protein/p300 (CBP/p300), and p300 using THP-1 cells. Histone acetyltransferase (HAT), histone deacetylase (HDAC), and pro-inflammatory cytokine secretion activity were analyzed using an enzyme-linked immunosorbent assay. RESULTS: HG significantly upregulated histone acetylation, acetylation levels of p300, NF-κB activation, and inflammatory cytokine release in THP-1 cells. Conversely, the NaB treatment reduced cytokine release and NF-κB activation in HG-treated cells. It also significantly reduced p65 acetylation, CBP/p300 HAT activity, and CBP/p300 gene expression. In addition, NaB decreased the interaction of p300 in acetylated NF-κB and TNF-α. CONCLUSIONS: These results suggest that NaB suppresses HG-induced inflammatory cytokine production through HAT/HDAC regulation in monocytes. NaB has the potential for preventing and treating diabetes and its related complications.

• Journal of Microbiology and Biotechnology
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• v.33 no.4
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• pp.430-440
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• 2023

The type three secretion system (T3SS) is a major virulence system of Pseudomonas aeruginosa (P. aeruginosa). The effector protein Exotoxin S (ExoS) produced by P. aeruginosa is secreted into the host cells via the T3SS. For the purpose of an experiment on inhibitors with regard to ExoS secretion, we developed a sandwich-type enzyme-linked immunosorbent assay (ELISA) system. Quercetin was selected because it has a prominent ExoS inhibition effect and also is known to have anti-inflammatory and antioxidant effects on mammalian cells. In this study, we investigated the effects of quercetin on the expression and secretion of ExoS using ELISA and Western blot analysis methods. The results showed that the secretion of ExoS was significantly decreased by 10 and 20 µM of quercetin. Also, popB, popD, pscF, and pcrV which are composed of the T3SS needle, are reduced by quercetin at the mRNA level. We also confirmed the inhibitory effect of quercetin on cytokines (IL-6, IL-1β, and IL-18) in P. aeruginosa-infected H292 cells by real-time polymerase chain reaction (PCR) and ELISA. Collectively, quercetin inhibits the secretion of ExoS by reducing both ExoS production and the expression of the needle protein of T3SS. Furthermore, these results suggest that quercetin has the potential to be used as an anti-toxic treatment for the inflammatory disease caused by P. aeruginosa infection.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.1
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• pp.127-134
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• 2009

In the present study, we investigated the anti-allergic effect of the water extract of Bopyeoyangyeong-jun(BYJ) to cytokines and transcription. To investigate the biological effect of BYJ, We examined cytotoxicity and inflammatory cytokine secretion with RBL-2H3. We examined tumor necrosis factor-alpha(TNF-$\alpha$), interleukin(IL)-4 secretion from RBL-2H3 cell after pre- treatment with Bopyeoyangyeong-jun of $1\;mg/m{\ell}$, $2\;mg/m{\ell}$. RBL-2H3 cell was stimulated with phorbol 12-myristate 13-acetate(PMA) and calcium ionophore A23187. We observed that Bopyeoyangyeong-jun reduced TNF-$\alpha$, IL-4 secretion and mRNA expression in RBL-2H3 cells. Moreover, the expression of levels of cyclooxygenase (COX)-2 mRNA, nuclear factor-kappa B (NF-${\kappa}B$) (p65) protein, ERK MAPK, and the degradation of level inhibitor kappa B-alpha ($I{\kappa}B-{\alpha}$) were down-regulated by BYJ. Taken together, these results indicate that Bopyeoyangyeong-jun hascontrols TNF-$\alpha$, IL-4 secretion on allergic reaction.

• 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 Korean Obstetrics and Gynecology
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• v.34 no.4
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• pp.12-29
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• 2021

Objective: This study was performed to investigate the inhibitory effect of Cheongpochukeo-tang (CCT) on lipopolysaccharide (LPS)-induced inflammation model. Methods: RAW 264.7 cells were pre-treated with CCT and incubated with LPS (500 ng/ml) after 1 hour. Cell viability was measured by MTT assay to figure out cytotoxicity of CCT. The production of nitric oxide and mRNA expression of pro-inflammatory cytokine were measured. And the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) were examined to figure out molecular mechanisms of CCT's anti-inflammatory effects. In addition, mice survival rate and cytokine levels of serum were observed after treated with CCT. And mice liver tissues were observed and their cytokines levels in liver tissue were measured. Results: CCT did not have cytotoxic effect in RAW 264.7 cells. It inhibited LPS-induced nitric oxide (NO) production, but showed an increase in NO by itself at 2 mg/ml concentration. CCT inhibited mRNA expression of IL-1β, IL-6, TNF-α in a dose dependant and the activaton of MAPKs and NF-κB. In addition, CCT reduced mortality in the LPS-induced mouse model and inhibited production of cytokines in mouse serum and liver tissue. Conclusion: The results suggest that CCT could reduce LPS-induced inflammation by inhibiting MAPKs and NF-κB activaton, NO production, and pro-inflammatory cytokines secretion. Thereby, CCT could be effective medicine for the inflammatory disease.

• Journal of the Korea Convergence Society
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• v.8 no.1
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• pp.239-243
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• 2017

This study aims to demonstrate the inhibitory effect of proinflammatory cytokines by using Frankinsense. The present data was designed to determine the production of the frankincence on pro-inflammatory factors such as $TNF-{\alpha}$ and $IL-1{\beta}$ in lipopolysaccharide(LPS) stimulated RAW264.7 macrophages cell. The cell toxicity was identified by CellTiter 96 AQueous One solution cell proliferation assay. To evaluate of anti-inflammatory effect of frankincence, pro-inflammatory cytokines were measured by ELISA kit. As a result, the frankincence reduced NO and $TNF-{\alpha}$ production without cytotoxicity. As a result, Francincense was not cytotoxic at 10 ug / ml-1000 ug / ml and significantly inhibited the proinflammatory cytokines $TNF-{\alpha}$ and $IL-1{\beta}$. The secretion inhibition effect of proinflammatory cytokine is believed to be applicable to various physiological activity data and functional materials to demonstrate the anti - inflammatory properties of frankincense.

• The Journal of Korean Medicine
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• v.39 no.4
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• pp.40-50
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• 2018

Objectives: The aim of this study is to investigate anti-inflammatory effects of Kyungheechunggan-tang (KHCGT) on LPS- induced RAW 264.7 cells and LX-2 cells and anti-fibrotic effects of KHCGT on LX-2 cells. Materials and Methods: Three types of KHCGTs (KHCGT-A, -B, and -C) by narrowing down the number of constituent herbs from 9 (KHCGT-A) to 5 (KHCGT-B) and to 3 (KHCGT-C) were developed. To understand pharmacological effects of KHCGT, three types of KHCGTs were treated on RAW 264.7 cells and LX-2 cells. Anti-inflammatory activities of KHCGT were evaluated by ELISA assay for pro-inflammatory cytokines, IL-6, $TNF-{\alpha}$ and IL-10, in LPS-stimulated RAW 264.7 cells and for IL-6 production in LPS-induced LX-2 cells. In addition, anti-fibrotic effects of KHCGT were determined by quantitative real-time PCR assay for fibrosis-related genes, ${\alpha}-SMA$, collagen1A1, TIMP1, MMP-2, in LX-2 cells. Results: KHCGT-A and KHCGT-C showed inhibitory effects on secretion of IL-6 in LPS-stimulated RAW 264.7 cells and LX-2 cells. KHCGT-B and KHCGT-C exhibited inhibitory effects on the expression of pro-inflammatory cytokines such as IL-6, $TNF-{\alpha}$, and IL-10 in LPS-stimulated RAW 264.7 cells. The mRNA expression levels of collagen1A1 and MMP-2 were significantly reduced by KHCGT-C whereas TIMP-1 was suppressed by KHCGT-A and KHCGT-B in LX-2 cells. Among three different formulas, KHCGT-C demonstrated the most remarkable effects on inflammation and fibrosis. Conclusions: In this study, KHCGT showed both anti-inflammatory and anti-fibrotic effects which make it to be a prospective agent for chronic liver diseases with inflammation and fibrosis.