• The Korea Journal of Herbology
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• v.23 no.4
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• pp.81-89
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• 2008

Objectives: In this study, the pharmacological effects of the ethylacetate extract of Ostericum koreanum(North Kangwhal; NK) on allergic inflammation were investigated in activated human mast cells. Methods: North Kangwhal was extracted with 80% methanol for 24 h, and then fractionated with ethylacetate(NK-EtOAc extract). HMC-1 cells, an human mast line, were pre-incubated with different concentrations of NK-EtOAc extract for 30 min, and then stimulated with PMA(50 nM/ml) and A23187($1{\mu}M/ml$) at indicated times. The cell toxicity was determined by MTT assay. The concentrations of prostaglandin E2(PGE2) and cytokines(TNF-${\alpha}$, IL-8) were measured by enzyme-linked immunosorbant assay. Results: NK-EtOAc extract($10{\sim}50{\mu}g/ml$) significantly inhibited the productions of $PGE_2$, TNF-${\alpha}$ and IL-8 in PMA/A23187-stimulated HMC-1 cells without cell toxicity($0{\sim}50{\mu}g/ml$). NK-EtOAc extract also inhibited PMA/A23187-induced phosphorylation of ERK1/2 MAPK and the NF-${\kappa}B$ p65 subunit translocation into the nuclear of HMC-1 cells. Conclusions: This study suggests that NK-EtOAc extract may have an anti-inflammatory property through suppressing the production of inflammatory mediators in activated mast cells and its molecular mechanism underlies the blocking of NF-${\kappa}B$ pathway.

• BMB Reports
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• v.50 no.1
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• pp.25-30
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• 2017

In the central nervous system, viral infection can induce inflammation by up-regulating pro-inflammatory mediators that contribute to enhanced infiltration of immune cells into the central nervous areas. Celastrol is known to exert various regulatory functions, including anti-microbial activities. In this study, we investigated the regulatory effects and the mechanisms of action of celastrol against astrocytes activated with polyinosinic-polycytidylic acid (poly(I:C)), a synthetic dsRNA, as a model of pro-inflammatory mediated responses. Celastrol significantly inhibited poly(I:C)-induced expression of adhesion molecules, such as ICAM-1/VCAM-1, and chemokines, such as CCL2, CXCL8, and CXCL10, in CRT-MG human astroglioma cells. In addition, celastrol significantly suppressed poly(I:C)-induced activation of JNK MAPK and STAT1 signaling pathways. Furthermore, celastrol significantly suppressed poly(I:C)-induced activation of the $NF-{\kappa}B$ signaling pathway. These results suggest that celastrol may exert its regulatory activity by inhibiting poly(I:C)-induced expression of pro-inflammatory mediators by suppressing activation of JNK MAPK-STAT1/$NF-{\kappa}B$ in astrocytes.

• Parasites, Hosts and Diseases
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• v.51 no.3
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• pp.289-295
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• 2013

Different functions have been attributed to $CD4^+CD25^+Foxp3^+$ regulatory T-cells (Tregs) during malaria infection. Herein, we describe the disparity in Treg response and pro- and anti-inflammatory cytokines during infection with Plasmodium berghei ANKA between young (3-week-old) and middle-aged (8-month-old) C57BL/6 mice. Young mice were susceptible to cerebral malaria (CM), while the middle-aged mice were resistant to CM and succumbed to hyperparasitemia and severe anemia. The levels of pro-inflammatory cytokines, such as TNF-${\alpha}$, in young CM-susceptible mice were markedly higher than in middle-aged CM-resistant mice. An increased absolute number of Tregs 3-5 days post-inoculation, co-occurring with elevated IL-10 levels, was observed in middle-aged CM-resistant mice but not in young CM-susceptible mice. Our findings suggest that Treg proliferation might be associated with the suppression of excessive pro-inflammatory Th1 response during early malaria infection, leading to resistance to CM in the middle-aged mice, possibly in an IL-10-dependent manner.

• IMMUNE NETWORK
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• v.11 no.1
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• pp.59-67
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• 2011

Background: Insulin resistance is an integral feature of metabolic syndromes, including obesity, hyperglycemia, and hyperlipidemia. In this study, we evaluated whether the aloe component could reduce obesity-induced inflammation and the occurrence of metabolic disorders such as blood glucose and insulin resistance. Methods: Male C57BL/6 obese mice fed a high-fat diet for 54 days received a supplement of aloe formula (PAG, ALS, Aloe QDM, and Aloe QDM complex) or pioglitazone (PGZ) and were compared with unsupplemented controls (high-fat diet; HFD) or mice fed a regular diet (RD). RT-PCR and western blot analysis were used to quantify the expression of obesity-induced inflammation. Results: Aloe QDM lowered fasting blood glucose and plasma insulin compared with HFD. Obesity-induced inflammatory cytokine (IL-$1{\beta}$, -6, -12, TNF-${\alpha}$) and chemokine (CX3CL1, CCL5) mRNA and protein were decreased markedly, as was macrophage infiltration and hepatic triglycerides by Aloe QDM. At the same time, Aloe QDM decreased the mRNA and protein of $PPAR{\gamma}/LXR{\alpha}$ and $11{\beta}$-HSD1 both in the liver and WAT. Conclusion: Dietary aloe formula reduces obesity-induced glucose tolerance not only by suppressing inflammatory responses but also by inducing anti-inflammatory cytokines in the WAT and liver, both of which are important peripheral tissues affecting insulin resistance. The effect of Aloe QDM complex in the WAT and liver are related to its dual action on $PPAR{\gamma}$ and $11{\beta}$-HSD1 ression and its use as a nutritional intervention against T2D and obesity-related inflammation is suggested.

• Journal of Periodontal and Implant Science
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• v.43 no.4
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• pp.191-197
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• 2013

Purpose: Nitric oxide (NO) is a short-lived bioactive molecule that is known to play an important role in the pathogenesis of periodontal disease. In the current study, we investigated the effect of the flavonoid quercetin on the production of NO in murine macrophages activated with lipopolysaccharide (LPS) from Prevotella intermedia, a pathogen related to inflammatory periodontal disease, and tried to elucidate the underlying mechanisms of action. Methods: LPS was isolated from P. intermedia ATCC 25611 cells by the standard hot phenol-water method. The concentration of NO in cell culture supernatants was determined by measuring the accumulation of nitrite. Inducible NO synthase (iNOS) and heme oxygenase-1 (HO-1) protein expression, phosphorylation of c-Jun N-terminal kinase (JNK) and p38, inhibitory ${\kappa}B$ $(I{\kappa}B)-{\alpha}$ degradation, and signal transducer and activator of transcription 1 (STAT1) phosphorylation were analyzed via immunoblotting. Results: Quercetin significantly attenuated iNOS-derived NO production in RAW246.7 cells activated by P. intermedia LPS. In addition, quercetin induced HO-1 protein expression in cells activated with P. intermedia LPS. Tin protoporphyrin IX (SnPP), a competitive inhibitor of HO-1, abolished the inhibitory effect of quercetin on LPS-induced NO production. Quercetin did not affect the phosphorylation of JNK and p38 induced by P. intermedia LPS. The degradation of $I{\kappa}B-{\alpha}$ induced by P. intermedia LPS was inhibited when the cells were treated with quercetin. Quercetin also inhibited LPS-induced STAT1 signaling. Conclusions: Quercetin significantly inhibits iNOS-derived NO production in murine macrophages activated by P. intermedia LPS via anti-inflammatory HO-1 induction and inhibition of the nuclear factor-${\kappa}B$ and STAT1 signaling pathways. Our study suggests that quercetin may contribute to the modulation of host-destructive responses mediated by NO and appears to have potential as a novel therapeutic agent for treating inflammatory periodontal disease.

• Exercise Science
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• v.26 no.3
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• pp.223-228
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• 2017

PURPOSE: This study investigated the protective role of high-intensity interval training against acute liver injury induced by D-galactosamine (D-Gal)/lipopolysaccharide (LPS). METHODS: A total of 30 male BALB/c mice aged 5-week were randomly assigned to high-intensity, interval training group (EX, n=10) or control group in cage (Non-EX, n=20) for 10 weeks. Peritoneal injection of D-Gal (700 mg/kg body weight) and LPS ($10{\mu}g/kg$ body weight) was applied to induce acute liver injury, and liver tissue was harvested 6 hours after the injection. Hematoxylin and Eosin (H&E) staining was used for liver histology. Real-time PCR was used to quantify expression of pro-inflammatory and anti-inflammatory genes in the liver. RESULTS: The liver histology showed that D-Gal/LPS treatment resulted in hepatic damage and increased number of neutrophils in conjunction with upregulation of hepatic IL-6 and $TNF-{\alpha}$ mRNAs and downregulation of hepatic $PPAR{\alpha}$ and SIRT1 mRNAs. On the other hand, the 10-week interval training resulted in a significant improvement in cardiorespiratory fitness assessed as run time to exhaustion on a treadmill. In addition, the interval training attenuated the D-Gal/LPS-induced liver damage and increased number of neutrophil in conjunction with downregulation of hepatic IL-6 and $TNF-{\alpha}$ mRNAs and upregulation of hepatic $PPAR{\alpha}$ and SIRT1 mRNAs. CONCLUSIONS: This study suggests that high-intensity interval training suppresses the D-Gal and LPS-induced acute liver damage and inflammatory responses.

• Nutrition Research and Practice
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• v.15 no.1
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• pp.26-37
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• 2021

BACKGROUND/OBJECTIVES: Hyperuricemic nephropathy is a common cause of acute kidney injury. Resveratrol can ameliorate kidney injury, but the explicit mechanism remains unclear. We investigated the effects of resveratrol on the inflammatory response and renal injury in hyperuricemic rats. MATERIALS/METHODS: A rat model of hyperuricemic nephropathy was established by the oral administration of a mixture of adenine and potassium oxinate. Biochemical analysis and hematoxylin and eosin staining were performed to assess the rat kidney function. Enzyme-linked immunosorbent assays were performed to evaluate the immune and oxidative responses. RESULTS: The expression levels of urine albumin and β2-microglobulin were significantly decreased after resveratrol treatment. In addition, the levels of serum creatinine and uric acid were significantly decreased in the resveratrol groups, compared with the control group. The levels of proinflammatory factors, such as interleukin-1β and tumor necrosis factor-α, in kidney tissue and serum were also increased in the hyperuricemic rats, and resveratrol treatment inhibited their expression. Moreover, the total antioxidant capacity in kidney tissue as well as the superoxide dismutase and xanthine oxidase levels in serum were all decreased by resveratrol treatment. CONCLUSIONS: Resveratrol may protect against hyperuricemic nephropathy through regulating the inflammatory response.

• Journal of Animal Science and Technology
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• v.64 no.1
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• pp.123-134
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• 2022

Toll-like receptors (TLRs), as a part of innate immunity, plays an important role in detecting pathogenic molecular patterns (PAMPs) which are structural components or product of pathogens and initiate host defense systems or innate immunity. Precise negative feedback regulations of TLR signaling are important in maintaining homeostasis to prevent tissue damage by uncontrolled inflammation during innate immune responses. In this study, we identified and characterized the function of the pancreatic progenitor cell differentiation and proliferation factor (PPDPF) as a negative regulator for TLR signal-mediated inflammation in chicken. Bioinformatics analysis showed that the structure of chicken PPDPF evolutionarily conserved amino acid sequences with domains, i.e., SH3 binding sites and CDC-like kinase 2 (CLK2) binding sites, suggesting that relevant signaling pathways might contribute to suppression of inflammation. Our results showed that stimulation with polyinosinic:polycytidylic acids (Poly [I:C]), a synthetic agonist for TLR3 signaling, increased the mRNA expression of PPDPF in chicken fibroblasts DF-1 but not in chicken macrophage-like cells HD11. In addition, the expression of pro-inflammatory genes stimulated by Poly(I:C) were reduced in DF-1 cells which overexpress PPDPF. Future studies warrant to reveal the molecular mechanisms responsible for the anti-inflammatory capacity of PPDPF in chicken as well as a potential target for controlling viral resistance.

• The Journal of Internal Korean Medicine
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• v.43 no.6
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• pp.1089-1104
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• 2022

Objective: The aim of this study was to identify the efficacy and underlying mechanism of cloves as an osteoarthritis (OA) treatment in a monosodium iodoacetate (MIA)-induced rat OA model. Osteoarthritis (OA) is nowadays one of the most prevalent degenerative joint diseases. Methods: Sprague-Dawley rats treated with MIA (50 μL; 80 mg/mL) were used as in vivo OA models. Cloves (100 and 200 mg/kg b.w.) were administered orally once daily for 2 weeks from 7 days after MIA injection. Changes in hindpaw weight distribution (HWD) were measured as a joint discomfort index. Activation markers related to inflammatory responses and cartilage degeneration in the right knee joints were evaluated by serum analysis and western blotting. Results: HWD decreased in the MIA control group but showed a dose-dependent elevation after clove treatment. Clove treatment inhibited inflammatory factors by PI3K/Akt/NF-κB signaling pathways, while also activating antioxidant factors through Sirt1/AMPK signaling pathways. Clove treatment also suppressed matrix metalloproteinase (MMP) overexpression and significantly increased the levels of tissue inhibitors of metalloproteinases (TIMPs). Conclusions: Treatment with cloves effectively reversed MIA-induced effects. Therefore, clove treatment could have the potential to protect against or treat OA.

• Korean Journal of Food Science and Technology
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• v.52 no.5
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• pp.467-475
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• 2020

Ultraviolet radiation is a major cause of photoaging, characterized by wrinkle formation and skin dehydration. Mojaban (Sargassum fulvellum), belonging to the brown algae of the Sargassaceae family, exerts anti-inflammatory, antioxidant, and anti-atopic activities. Particularly, Mojaban extract alleviated ultraviolet B (UVB)-induced inflammatory responses in human keratinocytes and BALB/c mice. Here, the dorsal skin of hairless mice was exposed to UVB for photoaging. The mice were administrated 300 mg/kg Mojaban extract (S. fulvellum extract; SFE) daily. Phenotypically, SFE reduced wrinkle formation and epidermal thickness and increased skin elasticity. SFE increased hydroxyproline content by upregulating the expression of collagen-related genes and downregulating matrix metalloproteinase expression. Furthermore, SFE increased skin moisture content and inhibited transepidermal water loss. SFE upregulated the expression of involucrin, loricrin, and transglutaminase for cornified envelope formation as well as the expression of filaggrin and caspase-14 for natural moisturizing factors. Collectively, SFE may be employed as a nutraceutical ingredient for anti-photoaging.