• Journal of Ginseng Research
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• 제45권6호
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• pp.717-725
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• 2021

Background: Korean Red Ginseng (KRG) is a traditional herb that has several beneficial properties including anti-aging, anti-inflammatory, and autophagy regulatory effects. However, the mechanisms of these effects are not well understood. In this report, the underlying mechanisms of anti-inflammatory and autophagy-promoting effects were investigated in aged mice treated with KRG-water extract (WE) over a long period. Methods: The mechanisms of anti-inflammatory and autophagy-promoting activities of KRG-WE were evaluated in kidney, lung, liver, stomach, and colon of aged mice using semi-quantitative reverse transcription polymerase chain reaction (RT-PCR), quantitative RT-PCR (qRT-PCR), and western blot analysis. Results: KRG-WE significantly suppressed the mRNA expression levels of inflammation-related genes such as interleukin (IL)-1β, IL-8, tumor necrosis factor (TNF)- α, monocyte chemoattractant protein-1 (MCP-1), and IL-6 in kidney, lung, liver, stomach, and colon of the aged mice. Furthermore, KRG-WE downregulated the expression of transcription factors and their protein levels associated with inflammation in lung and kidney of aged mice. KRG-WE also increased the expression of autophagy-related genes and their protein levels in colon, liver, and stomach. Conclusion: The results suggest that KRG can suppress inflammatory responses and recover autophagy activity in aged mice.

• Journal of Applied Biological Chemistry
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• 제64권3호
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• pp.277-284
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• 2021

The emergence and rapid spread of the potentially fatal coronavirus disease 2019, caused due to infection by severe acute respiratory syndrome coronavirus-2, has led to worldwide interest in developing functional bioactive ingredients that act as immunomodulatory agents. In this study, we aimed to characterize Carica papaya extract and explore its potential as an immunomodulator by performing in vitro cell screening. Papaya leaf water extract (PLW) was found to significantly increase the levels of nitric oxide (NO) and prostaglandin E₂ (PGE₂) by upregulating inducible nitric oxide synthase and cyclo-oxygenase-2 activity, respectively. Additionally, PLW increased the production of tumor necrosis factor-α and interleukin 1β in RAW 264.7 cells. Furthermore, PLW activated the expression of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) but not that of p38 mitogen-activated protein kinase. These results indicate that PLW increased the production of NO, PGE₂, and pro-inflammatory cytokines by activating the JNK and ERK pathways in macrophages, thus demonstrating immunomodulatory properties. Finally, high-performance liquid chromatography fingerprint analysis indicated the presence of rutin, narirutin, and ρ-coumaric acid in PLW (6.30, 119.76, and 47.25 ppm, respectively). Treating cells with these compounds at non-toxic concentrations had no effect on NO production. Taken together, these results suggest that PLW may have potential as an immunity-enhancing supplement.

• Journal of Veterinary Science
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• 제22권2호
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• pp.20.1-20.13
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• 2021

Background: Pseudorabies virus (PRV) infection leads to high mortality in swine. Despite extensive efforts, effective treatments against PRV infection are limited. Furthermore, the inflammatory response induced by PRV strain GXLB-2013 is unclear. Objectives: Our study aimed to investigate the inflammatory response induced by PRV strain GXLB-2013, establish an inflammation model to elucidate the pathogenesis of PRV infection further, and develop effective drugs against PRV infection. Methods: Kunming mice were infected intramuscularly with medium, LPS, and different doses of PRV-GXLB-2013. Viral spread and histopathological damage to brain, spleen, and lung were determined at 7 days post-infection (dpi). Immune organ indices, levels of reactive oxygen species (ROS), nitric oxide (NO), and inflammatory cytokines, as well as levels of activity of COX-2 and iNOS were determined at 4, 7, and 14 dpi. Results: At 10⁵-10⁶ TCID₅₀ PRV produced obviously neurological symptoms and 100% mortality in mice. Viral antigens were detectable in kidney, heart, lung, liver, spleen, and brain. In addition, inflammatory injuries were apparent in brain, spleen, and lung of PRV-infected mice. Moreover, PRV induced increases in immune organ indices, ROS and NO levels, activity of COX-2 and iNOS, and the content of key pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, tumor necrosis factor-α, interferon-γ and MCP-1. Among the tested doses, 10² TCID₅₀ of PRV produced a significant inflammatory mediator increase. Conclusions: An inflammatory model induced by PRV infection was established in mice, and 10² TCID50 PRV was considered as the best concentration for the establishment of the model.

• Journal of Microbiology and Biotechnology
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• 제31권8호
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• pp.1115-1122
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• 2021

Rotavirus (RV), as the main cause of diarrhea in children under 5 years, contributes to various childhood diseases. Valeriana jatamansi Jones is a traditional Chinese herb and possesses antiviral effects. In this study we investigated the potential mechanisms of V. jatamansi Jones in RV-induced diarrhea. MTT assay was performed to evaluate cell proliferation and the diarrhea mice model was constructed using SA11 infection. Mice were administered V. jatamansi Jones and ribavirin. Diarrhea score was used to evaluate the treatment effect. The enzyme-linked immunosorbent assay was performed to detect the level of cytokines. Western blot and quantitative reverse transcription-PCR were used to determine protein and mRNA levels, respectively. Hematoxylin-eosin staining was applied to detect the pathological change of the small intestine. TdT-mediated dUTP nick-end labeling was conducted to determine the apoptosis rate. The results showed V. jatamansi Jones promoted MA104 proliferation. V. jatamansi Jones downregulated phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) in protein level, which was consistent with the immunohistochemistry results. Moreover, V. jatamansi Jones combined with ribavirin regulated interleukin-1β (IL-1β), interferon γ, IL-6, tumor necrosis factor α, and IL-10, and suppressed secretory immunoglobulin A secretion to remove viruses and inhibit dehydration. V. jatamansi Jones + ribavirin facilitated the apoptosis of small intestine cells. In conclusion, V. jatamansi Jones may inhibit RV-induced diarrhea through PI3K/AKT signaling pathway, and could therefore be a potential therapy for diarrhea.

• 대한한방부인과학회지
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• 제34권4호
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• pp.1-11
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• 2021

Objectives: Nephrotic syndrome is a kidney disorder, which is characterized by proteinuria, edema (swelling), and hyperlipidemia. Maydis Stigma (Corn silk) has been widely used in Asia as a traditional medicine and is known to have a diuretic effect and is used for the treatment of edema and indigestion. Methods: The aim of this study is to investigate the improvement effect of Maydis Stigma in treating nephrotic syndrome induced by puromycin aminonucleoside. Sprague-Dawley rats were intravenously injected with 75 mg/kg/day puromycin aminonucleoside, then treated with either Losartan or 200 mg/kg/day Maydis Stigma for seven days. Results: Maydis Stigma significantly decreased ascites and proteinuria level. Plasma levels of blood urea nitrogen (BUN) and plasma creatinine reduced significantly by Maydis Stigma. In addition, treatment with Maydis Stigma attenuated histological damage. Treatment with Maydis Stigma also restored podocin expression and reduced inflammation markers such as intracellular adhesion molecules (ICAM-1), monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor alpha (TNF-α) and high-mobility group box-1 (HMGB1). Conclusions: Maydis Stigma ameliorates kidney injury in nephrotic syndrome rat models. Maydis Stigma exerts a renoprotective effect owing to its anti-inflammatory effects and reductions of ascites and proteinuria. Thus, these results indicate that Maydis Stigma is likely to be a promising agent in the treatment of nephrotic syndrome.

• Nutrition Research and Practice
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• 제15권1호
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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.

• The Korean Journal of Physiology and Pharmacology
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• 제25권2호
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• pp.97-109
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• 2021

Neonatal hypoxia/ischemia (H/I), injures white matter, results in neuronal loss, disturbs myelin formation, and neural network development. Neuroinflammation and oxidative stress have been reported in neonatal hypoxic brain injuries. We investigated whether Paeoniflorin treatment reduced H/I-induced inflammation and oxidative stress and improved white matter integrity in a neonatal rodent model. Seven-day old Sprague-Dawley pups were exposed to H/I. Paeoniflorin (6.25, 12.5, or 25 mg/kg body weight) was administered every day via oral gavage from postpartum day 3 (P3) to P14, and an hour before induction of H/I. Pups were sacrificed 24 h (P8) and 72 h (P10) following H/I. Paeoniflorin reduced the apoptosis of neurons and attenuated cerebral infarct volume. Elevated expression of cleaved caspase-3 and Bad were regulated. Paeoniflorin decreased oxidative stress by lowering levels of malondialdehyde and reactive oxygen species generation and while, and it enhanced glutathione content. Microglial activation and the TLR4/NF-κB signaling were significantly down-regulated. The degree of inflammatory mediators (interleukin 1β and tumor necrosis factor-α) were reduced. Paeoniflorin markedly prevented white matter injury via improving expression of myelin binding protein and increasing O1-positive olidgodendrocyte and O4-positive oligodendrocyte counts. The present investigation demonstrates the potent protective efficiency of paeoniflorin supplementation against H/I-induced brain injury by effectually preventing neuronal loss, microglial activation, and white matter injury via reducing oxidative stress and inflammatory pathways.

• Journal of Microbiology and Biotechnology
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• 제32권2호
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• pp.228-237
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• 2022

In this study, the effects of the immune stimulator Euglena gracilis (Euglena) in cyclophosphamide (CCP)-induced immunocompromised mice were assessed. The key component β-1,3-glucan (paramylon) constitutes 50% of E. gracilis. Mice were orally administered Euglena powder (250 and 500 mg/kg body weight (B.W.)) or β-glucan powder (250 mg/kg B.W.) for 19 days. In a preliminary immunology experiment, ICR mice were intraperitoneally injected with 80 mg of CCP/kg B.W. during the final 3 consecutive days. In the main experiment, BALB/c mice were treated with CCP for the final 5 days. To evaluate the enhancing effects of Euglena on the immune system, mouse B.W., the spleen index, natural killer (NK) cell activity and mRNA expression in splenocytes lungs and livers were determined. To detect cytokine and receptor expression, splenocytes were treated with 5 ㎍/ml concanavalin A or 1 ㎍/ml lipopolysaccharide. The B.W. and spleen index were significantly increased and NK cell activity was slightly enhanced in all the experimental groups compared to the CCP-only group. In splenocytes, the gene expression levels of tumor necrosis factor-α, interferon-γ, interleukin (IL)-10, IL-6, and IL-12 receptor were increased in the E. gracilis and β-glucan groups compared to the CCP-only group, but there was no significant difference. Treatment with 500 mg of Euglena/kg B.W. significantly upregulated dectin-1 mRNA expression in the lung and liver compared to the CCP-only group. These results suggest that Euglena may enhance the immune system by strengthening innate immunity through immunosuppression.

• 한국미생물·생명공학회지
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• 제50권1호
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• pp.22-30
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• 2022

Haliotis discus hannai called abalone, is the valuable marine mollusks and the by-products of abalone processing are viscera. Brownish abalone male viscera (AMV), which have not been reported as having anti-inflammatory effects, was extracted with acetone and fractionated by different six acetone/hexane ratios (0, 10, 20, 30, 40, and 100%) using a silica column via in vitro ABTS and DPPH radical and nitric oxide (NO) production assay-guided fractionation. Among the fractions, the acetone/hexane ratio 40%, A40 exhibited the most potent radical scavenging activities and inhibition of lipopolysaccharide (LPS)-induced NO production without cytotoxicity. A40 inhibited LPS-induced intracellular reactive oxygen species (ROS) production in a dose-dependent manner. Western blot analysis revealed that A40 down-regulated the activation of NF-κB, MAPK (ERK 1/2, p-38, and JNK), and inflammatory enzymes, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2. Moreover, this fraction inhibited the generation of pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. These results suggested that AMV containing A40 with anti-inflammatory and anti-oxidantive effects, is the effective therapeutic and functional material for treating inflammatory disorders.

• Molecules and Cells
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• 제44권12호
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• pp.893-899
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• 2021

BLT2 is a low-affinity receptor for leukotriene B₄, a potent lipid mediator of inflammation generated from arachidonic acid via the 5-lipoxygenase pathway. The aim of this study was to investigate whether BLT2 plays any role in sepsis, a systemic inflammatory response syndrome caused by infection. A murine model of cecal ligation and puncture (CLP)-induced sepsis was used to evaluate the role of BLT2 in septic inflammation. In the present study, we observed that the levels of ligands for BLT2 (LTB₄ [leukotriene B₄] and 12(S)-HETE [12(S)-hydroxyeicosatetraenoic acid]) were significantly increased in the peritoneal lavage fluid and serum from mice with CLP-induced sepsis. We also observed that the levels of BLT2 as well as 5-lipoxygenase (5-LO) and 12-LO, which are synthesizing enzymes for LTB₄ and 12(S)-HETE, were significantly increased in lung and liver tissues in the CLP mouse model. Blockade of BLT2 markedly suppressed the production of sepsis-associated cytokines (IL-6 [interleukin-6], TNF-α [tumor necrosis factor alpha], and IL-1β [interleukin-β] as well as IL-17 [interleukin-17]) and alleviated lung inflammation in the CLP group. Taken together, our results suggest that BLT2 cascade contributes to lung inflammation in CLP-induced sepsis by mediating the production of inflammatory cytokines. These findings suggest that BLT2 may be a potential therapeutic target for sepsis patients.