• Anatomy and Cell Biology
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• 제56권4호
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• pp.494-507
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• 2023

Vascular dementia (VaD) is characterized by progressive memory impairment, which is associated with microglia-mediated neuroinflammation. Polyphenol-rich natural plants, which possess anti-inflammatory activities, have attracted scientific interest worldwide. This study investigated whether Rubus fruticosus leaf extract (RFLE) can attenuate VaD. Sprague-Dawley rats were separated into five groups: SO, sham-operated and treated with vehicle; OP, operated and treated with vehicle; RFLE-L, operated and treated with low dose (30 mg/kg) of RFLE; RFLE-M, operated and treated with medium dose (60 mg/kg) of RFLE; and RFLE-H, operated and treated with high dose (90 mg/kg) of RFLE. Bilateral common carotid artery and hypotension were used as a modeling procedure, and the RFLE were intraorally administered for 5 days (preoperative 2 and postoperative 3 days). The rats then underwent memory tests including the novel object recognition, Y-maze, Barnes maze, and passive avoidance tests, and neuronal viability and neuroinflammation were quantified in their hippocampi. The results showed that the OP group exhibited VaD-associated memory deficits, neuronal death, and microglial activation in hippocampi, while the RFLE-treated groups showed significant attenuation in all above parameters. Next, using BV-2 microglial cells challenged with lipopolysaccharide (LPS), we evaluated the effects of RFLE in dynamics of proinflammatory mediators and the upstream signaling pathway. RFLE pretreatment significantly inhibited the LPS-induced release of nitric oxide, TNF-α, and IL-6 and upregulation of the MAPKs/NF-κB/iNOS pathway. Collectively, we suggest that RFLE can attenuate the histologic alterations and memory deficits accompanied by VaD, and these roles are, partly due to the attenuation of microglial activation.

• Journal of Ginseng Research
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• 제47권5호
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• pp.672-680
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• 2023

Background: Korean Red Ginseng (KRG), the steamed root of Panax ginseng, has pharmacological activities for immunological and neurodegenerative disorders. But, the role of KRGE in multiple sclerosis (MS) remains unclear. Purpose: To determine whether KRG extract (KRGE) could inhibit demyelination in corpus callosum (CC) of cuprizone (CPZ)-induced murine model of MS Methods: Male adult mice were fed with a standard chow diet or a chow diet supplemented with 0.2% (w/w) CPZ ad libitum for six weeks to induce demyelination while were simultaneously administered with distilled water (DW) alone or KRGE-DW (0.004%, 0.02 and 0.1% of KRGE) by drinking. Results: Administration with KRGE-DW alleviated demyelination and oligodendrocyte degeneration associated with inhibition of infiltration and activation of resident microglia and monocyte-derived macrophages as well as downregulation of proinflammatory mediators in the CC of CPZ-fed mice. KRGE-DW also attenuated the level of infiltration of Th1 and Th17) cells, in line with inhibited Mrna expression of IFN-γ and IL-17, respectively, in the CC. These positive effects of KRGE-DW mitigated behavioral dysfunction based on elevated plus maze and the rotarod tests. Conclusion: The results strongly suggest that KRGE-DW may inhibit CPZ-induced demyelination due to its oligodendroglial protective and anti-inflammatory activities by inhibiting infiltration/activation of immune cells. Thus, KRGE might have potential in therapeutic intervention for MS.

• Toxicological Research
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• 제34권1호
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• pp.65-73
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• 2018

Pretreatment of low-dose lipopolysaccharide (LPS) induces a hyporesponsive state to subsequent secondary challenge with high-dose LPS in innate immune cells, whereas super-low-dose LPS results in augmented expression of pro-inflammatory cytokines. However, little is known about the difference between super-low-dose and low-dose LPS pretreatments on immune cell-mediated inflammatory and hepatic acute-phase responses to secondary LPS. In the present study, RAW 264.7 cells, EL4 cells, and Hepa-1c1c7 cells were pretreated with super-low-dose LPS (SL-LPS: 50 pg/mL) or low-dose LPS (L-LPS: 50 ng/mL) in fresh complete medium once a day for 2~3 days and then cultured in fresh complete medium for 24 hr or 48 hr in the presence or absence of LPS ($1{\sim}10{\mu}g/mL$) or concanavalin A (Con A). SL-LPS pretreatment strongly enhanced the LPS-induced production of tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-6, TNF-${\alpha}$/IL-10, prostaglandin E2 ($PGE_2$), and nitric oxide (NO) by RAW 264.7 cells compared to the control, whereas L-LPS increased IL-6 and NO production only. SL-LPS strongly augmented the Con A-induced ratios of interferon (IFN)-${\gamma}$/IL-10 in EL4 cells but decreased the LPS-induced ratios of IFN-${\gamma}$/IL-10 compared to the control, while L-LPS decreased the Con A- and LPS-induced ratios of IFN-${\gamma}$/IL-10. SL-LPS enhanced the LPS-induced production of IL-6 by Hepa1c1c-7 cells compared to the control, while L-LPS increased IL-6 but decreased IL-$1{\beta}$ and C reactive protein (CRP) levels. SL-LPS pretreatment strongly enhanced the LPS-induced production of TNF-${\alpha}$, IL-6, IL-10, $PGE_2$, and NO in RAW 264.7 cells, and the IL-6, IL-$1{\beta}$, and CRP levels in Hepa1c1c-7 cells, as well as the ratios of IFN-${\gamma}$/IL-10 in LPS- and Con A-stimulated EL4 cells compared to L-LPS. These findings suggest that pre-conditioning of SL-LPS may contribute to the mortality to secondary infection in sepsis rather than pre-conditioning of L-LPS.

• Clinical and Experimental Pediatrics
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• 제56권11호
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• pp.482-489
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• 2013

Purpose: The aim of the present study was to investigate the differences in lower airway inflammatory immune responses, including cellular responses and responses in terms of inflammatory mediators in bronchoalveolar lavage fluid (BALF) and the airway, to rhinovirus (RV) infection on asthma exacerbation by comparing a control and a murine asthma model, with or without RV infection. Methods: BALB/c mice were intraperitoneally injected with a crude extract of Dermatophagoides farinae (Df ) or phosphate buffered saline (PBS) and were subsequently intranasally treated with a crude extract of Df or PBS. Airway responsiveness and cell infiltration, differential cell counts in BALF, and cytokine and chemokine concentrations in BALF were measured 24 hours after intranasal RV1B infection. Results: RV infection increased the enhanced pause (Penh) in both the Df sensitized and challenged mice (Df mice) and PBS-treated mice (PBS mice) (P<0.05). Airway eosinophil infiltration increased in Df mice after RV infection (P<0.05). The levels of interleukin (IL) 13, tumor necrosis factor alpha, and regulated on activation, normal T cells expressed and secreted (RANTES) increased in response to RV infection in Df mice, but not in PBS mice (P<0.05). The level of IL-10 significantly decreased following RV infection in Df mice (P<0.05). Conclusion: Our findings suggest that the augmented induction of proinflammatory cytokines, Th2 cytokines, and chemokines that mediate an eosinophil response and the decreased induction of regulatory cytokines after RV infection may be important manifestations leading to airway inflammation with eosinophil infiltration and changes in airway responsiveness in the asthma model.

• Journal of Chest Surgery
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• 제35권2호
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• pp.118-126
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• 2002

배경: 체외순환에 의해 생성되는 염증매개체는 소아 환자에서 술 후 다기관 기능부전과 연관이 있다. 본 연구에서는 선천성 신장질환 소아환자에서 체외순환에 의한 전염증성 사이토카인과 케모카인의 유전자 발현 특성에 대해 알아보고자 하였다. 대상 및 방법: 개심술을 시행한 18명의 소아 환자의 요골 동맥에서 마취유도 후(기준치), 체외순환(0시간), 체외순환 2시간 후 24시간 후, 48시간 후에 혈액을 채취하였다. 모든 환자에서 인터루킨-1알파, 인터루킨-1베타 인터루킨-6, 인터루킨-8, 종양괴사자인자-알파, 인터루킨-15,인터페론 감마의 mRNA의 유전자 발현 정도를 반정량적으로 역전사 중합효소 연쇄반응으로 측정하였다. 6명의 환자에서 인터루킨-6단백치는효소결합면역흡착검사로 측정하였다. 결과: 전신적인 인터루킨-6 mRNA와 비슷한 양상을 보였으나 최고치는 인터루킨-6보다 낮은 값을 보였다. 인터루킨-1알파와 인터루킨-1베타의 mRNA의 발현은 체외순환 2시간 후에 최고치를 나타내었고 체외순환 2시간 후에 최고치를 나타내었고 체외순환 48시간 후에 감소하였다. 종양괴사자인자-알파는 체외 순환 24시간 후에 최고치를 나타내었고 체외순환 48시간 후에 감소하였다. 인터루킨-15 mRNA 발현은 체외순환 전후와 비교하여 유의한 변화가 없었다. 인터페론-감마는 시간이 지남에 따라 감소하였다. 결론: 선천성 심장질환으로 개심술을 시행한 소아환자의 혈청 내 인터루킨-6, 인터루킨-8, 인터루킨-1알파, 인터루킨-베타, 종양괴사자인자-알파의 유전자 발현은 체외 순환 전후로 유의한 변화를 보였다. 인터루킨-15는 유의한 변화가 없었고 인터페론-감마는 반대 양상의 변화를 보였다. 체외순환 후 전염증성 사이토카인과 케모카인의 높은 혈중 농도는 술 후 조직 손상과 연관되리라 생각한다.

• 한국해양바이오학회지
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• 제13권2호
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• pp.86-93
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• 2021

A high salt diet contributes to kidney damage by causing hypoxia and oxidative stress. Recently, an increase in dietary salt has been reported to induce an inflammatory phenotype in immune cells, further contributing to kidney damage. However, studies on the exact mechanism and role of a high salt diet on the inflammatory response in the kidneys are still insufficient. In this study, a cisplatin-induced acute kidney injury model using C57BL/6 mice was used to analyze the effect of salt intake on kidney injury. Results showed that high salt administration aggravated kidney edema in mice induced by treatment with cisplatin. Moreover, the indicators of kidney and liver function impairment were significantly increased in the group cotreated with high salt compared with that treated with cisplatin alone. Furthermore, the exacerbation of kidney damage by high salt administration was also associated with a decrease in the number of cells in the immune regulatory system. Additionally, high salt administration further decreased renal perfusion functions along with increased cisplatin-induced damage to proximal tubules. This was accompanied by increased expression of T cell immunoglobulin, mucin domain 1 (a biomarker of kidney injury), and Bax (a pro-apoptotic factor). Moreover, cisplatin-induced expression of proinflammatory mediators and cytokines, including cyclooxygenase-2 and tumor necrosis factor-α in kidney tissue, was further increased by high salt intake. Therefore, these results indicate that the kidney's inflammatory response by high salt treatment can further promote kidney damage caused by various pathological factors.

• 대한한의학방제학회지
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• 제26권4호
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• pp.295-306
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• 2018

Schisandra chinensis (SC) and Lycium chinense (LC) were widely distributed in Asia and the fruit has been used traditionally for medicinal herbs. The processing method was solid-state fermentation using Aspergillus oryzae for 48 h after stir-frying treatment at $220^{\circ}C$ for 12 min. In this study, in vitro the anti-inflammatory effect and in vivo hangover reduction were compared to unprocessed SC and LC water extract. Anti-inflammatory effects have been evaluated in pro-inflammatory mediators which were secreted by lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. Nitric oxide (NO) was determined using Griess reaction. Proinflammatory cytokines such as tumor necrosis factor $(TNF)-{\alpha}$ and interleukin $(IL)-1{\beta}$ were measured by enzyme-linked immunosorbent assays (ELISA). Alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) activities were compared to processed SC or LC and mixtures thereof (1:1). In vivo study was compared to hangover relief in alcohol-fed mice. After administering a mixture of SC and LC (300 mg/kg) water extract (1:1), mice were fed 3 g/kg of ethanol. Serum was collected at 1, 3, and 5 h intervals to analyze ethanol and acetaldehyde levels using a colorimetric assay kit. The processed SC and LC water extracts compared to raw materials significantly inhibited LPS-induced NO and inflammatory cytokine production in RAW 264.7 cells. The results of the hangover mouse model are also consistent with anti-inflammatory effects. These results suggest that processed SC and LC extracts may be functional materials for the treatment of inflammation and hangover.

• 생명과학회지
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• 제28권11호
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• pp.1332-1338
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• 2018

뇌신경 질환의 주요 원인이 되는 것으로 알려진 미세아교세포의 과도한 활성화에 의한 신경염증반응에서 풀무치 에탄올 추출물이 미세아교세포의 염증 반응에 미치는 영향을 검토하였다. 미세아교세포의 활성화를 유도하기 위해 LPS를 사용하였으며, LPS 처리에 의해 신경염증반응의 지표인 NO의 생성량과 이들을 조절하는 iNOS, COX-2의 발현이 증가됨을 확인 할 수 있었다. 그러나 풀무치 에탄올 추출물을 1시간 전처리 한 후 LPS를 처리한 경우 추출물의 농도에 의존적으로 이들의 발현량이 현저히 감소되는 것을 확인 하였다. 또한 LPS 처리로 인해 분비되는 염증성 cytokine들의 생성량도 풀무치 에탄올 추출물에 의해 현저히 억제 됨을 확인 할 수 있었다. 따라서 본 연구의 결과는 미세아교세포의 과도한 활성화로 인해 발생되는 뇌 신경질환의 치료 소재로서 풀무치 에탄올 추출물의 활성 가능성을 제시하였다.

• 치위생과학회지
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• 제20권4호
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• pp.221-229
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• 2020

Background: The purpose of this study was to investigate the anti-oral microbial activity and anti-inflammatory effects of rosmarinic acid (RA) in lipopolysaccharide (LPS)-stimulated MC3T3-E1 osteoblastic cells on a titanium (Ti) surface during osseointegration, and to confirm the possibility of using RA as a safe natural substance for the control of peri-implantitis (PI) in Ti-based dental implants. Methods: A disk diffusion test was conducted to confirm the antimicrobial activity of RA against oral microorganisms. In order to confirm the anti-inflammatory effects of RA, inflammatory conditions were induced with 100 ng/ml of LPS in MC3T3-E1 osteoblastic cells on the Ti surface treated with or without 14 ㎍/ml of RA. The production of nitric oxide (NO) and prostaglandin E2 (PGE2) in LPS-stimulated MC3T3-E1 osteoblastic cells on the Ti surface was confirmed using an NO assay kit and PGE2 enzyme-linked immunosorbent assay kit. Reverse transcription polymerase chain reaction and western blot analysis were performed to confirm the expression of interleukin (IL)-1β and tumor necrosis factor (TNF)-α in total RNA and protein. Results: RA showed weak antimicrobial effects against Streptococcus mutans and Escherichia coli, but no antimicrobial activity against the bacteria Aggregatibacter actinomycetemcomitans and the fungus Candida albicans. RA reduced the production of pro-inflammatory mediators, NO and PGE2, and proinflammatory cytokines, TNF-α and IL-1β, in LPS-stimulated MC3T3-E1 osteoblastic cells on the Ti surface at the protein and mRNA levels. Conclusion: RA not only has anti-oral microbial activity, but also anti-inflammatory effects in LPS-stimulated MC3T3-E1 osteoblasts on the Ti surface, therefore, it can be used as a safe functional substance derived from plants for the prevention and control of PI for successful Ti-based implants.

• 대한본초학회지
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• 제28권3호
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• pp.53-60
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• 2013

Objectives : DojukSan is known to be effective for treating a urinary diseases and stomatitis. However, there has been a lack of studies regarding the effects of Dojuksan on the inflammatory activities and effector inflammatory disease mechanism about macrophage before is not known. To elucidate the molecular mechanisms of Dojuksan water extract (DJS) on pharmacological and biochemical actions in inflammation, we examined the effect of DJS on pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated macrophages. Methods : In the present study, pro-inflammatory cytokine production was determined by performing enzyme-linked immunosorbent assay, reverse transcription polymerase chain reaction, and western blot analysis to measure the activation of MAPKs. Cells were treated with 200 ng/mL of LPS 1 h prior to the addition of DJS. Cell viability was measured by MTS assay. The investigation focused on whether DJS inhibited nitric oxide (NO) and prostaglandin E2 ($PGE_2$) productions, as well as the expressions of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6) and mitogen-activated protein kinases (MAPKs) in LPS-stimulated RAW 264.7 cells. Results : We found that DJS inhibited LPS-induced NO, $PGE_2$ and IL-6 productions as well as the expressions of iNOS and COX-2. Furthermore, DJS suppressed the LPS-induced phosphorylation of p38 MAPK and c-Jun NH2-protein kinase (JNK). Conclusions : These results suggest that DJS has inhibitory effects on LPS-induced $PGE_2$, NO, and IL-6 production, as well as the expressions of iNOS and COX-2 in the murine macrophage. These inhibitory effects occur through blockades on the MAPKs phosphorylation.