• BMB Reports
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• 제51권12호
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• pp.654-659
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• 2018

Antioxidant 1 (ATOX1) protein has been reported to exhibit various protective functions, including antioxidant and chaperone. However, the effects of ATOX1 on the inflammatory response has not been fully elucidated. Thus, we prepared cell permeable Tat-ATOX1 and studied the effects on lipopolysaccharide (LPS)- and 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced inflammation. Experimental results showed that transduced Tat-ATOX1 protein significantly suppressed LPS-induced intracellular reactive oxygen species (ROS). Also, Tat-ATOX1 protein markedly inhibited LPS- and TPA-induced inflammatory responses by decreasing cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) and further inhibited phosphorylation of mitogen activated protein kinases (MAPKs; JNK, ERK and p38) and the nuclear factor-kappaB ($NF-{\kappa}B$) signaling pathway. These results indicate that the Tat-ATOX1 protein has a pivotal role in inflammation via inhibition of inflammatory responses, suggesting Tat-ATOX1 protein may offer a therapeutic strategy for inflammation.

• 대한한의학회지
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• 제40권2호
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• pp.51-62
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• 2019

Objectives: This study was designed to evaluate the macrophages polarization of traditional Korean medicine on cardiac pain about Geum-Gwe-Yo-Ryak's two prescriptions including Kwaruhaebaekbanha-tang (KHB) and Kwaruhaebaekpaekju-tang (KHP). Materials and methods: Flow cytometry analysis was used to measure the changes in the ratio of M1 type and M2 type macrophages. Protein expression of nuclear factor-like 2 (Nrf2), heme oxygenase-1 (HO-1), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) were measured by Western Blot, and ABCA1 and SR-B1 were detected by real time PCR (RT-PCR). Intracellular lipid accumulation was measured by Oil Red O staining (ORO staining). Results: KHB and KHP increase anti-oxidative activity related protein levels including Nrf2 and HO-1. Furthermore, KHB and KHP inhibit lipid accumulation on intracellular levels through induction of ATP binding receptor cassette subfamily A member 1 (ABCA1) and scavenging receptor class B member 1 (SR-B1), respectively. Finally, KHB and KHP also blocked pro-inflammatory mediators including tumor necrosis factor-alpha ($TNF{\alpha}$) and interleukin-6 (IL-6), iNOS and COX-2 expression. Conclusion: This study suggests that KHB and KHP potently regulate the M1/M2 macrophage polarization.

• Journal of Applied Biological Chemistry
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• 제62권1호
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• pp.39-50
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• 2019

Mitogen-activated protein (MAP) kinases play an important role in cell growth and differentiation, as well as the modulation of proinflammatory cytokines. The objective of this study was to examine the increase in the anti-inflammatory effect of Gentiana scabra Bunge (GSB), due to bioconversion with the Aspergillus kawachii crude enzyme, via inhibition of the $NF-{\kappa}B$ signaling and MAP kinase pathways in RAW 264.7 cells. The expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 in RAW 264.7 cells treated with the GSB ethyl acetate fraction bioconverted with A. kawachii crude enzyme (GE-BA), was dramatically suppressed as compared to GSB ethyl acetate fraction non-bioconverted with the A. kawachii crude enzyme (GE-UA). The phosphorylation of p38, extracellular signal-regulated kinases, and inhibitory ${\kappa}B$ in RAW 264.7 cells treated with GE-BA was further suppressed, as compared to exposure to GE-UA. Moreover, the mRNA expression of interleukin 6, interleukin 1-beta, and tumor necrosis $factor-{\alpha}$ was further suppressed by GE-BA, compared to GE-UA. Similarly, anti-oxidant activities, such as 2,2-diphenyl-1-picrylhydrazyl hydrate and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) radical scavenging activity, of GE-BA were further increased compared to GE-UA. These observations demonstrate that the anti-oxidant and anti-inflammatory activities of GSB ethyl acetate fraction increases as a result from bioconversion with the A. kawachii crude enzyme.

• 한국식생활문화학회지
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• 제34권1호
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• pp.84-92
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• 2019

Purpose: The objective of this study was conducted to investigate the effects of rutin, buckwheat components on cell growth and anti-inflammation in adipocyte 3T3-L1 and human colon cancer cell SW-480. Methods: We cultured 3T3-L1 adipocyte and SW-480 colon cancer cell to confluence, at which time starvation was induced with SFM for 1 day. Cells were then cultured in medium containing 0, 25, 50, or $100{\mu}mol/mL$ of rutin 3T3-L1 or 0, 10, 20, or $40{\mu}mol/mL$ SW-480. Cell viability was measured using a cell viability kit. In addition, we examined the expression of mRNA related to inflammation. RT-PCR was used to quantity tumor necrosis factor ($TNF-{\alpha}$), interleukin-$1{\beta}$ ($IL-1{\beta}$), IL-6, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) mRNA levels. Results: Rutin significantly inhibited 3T3-L1 and SW-480 cell proliferation in a dose and time dependent manner. Rutin also significantly reduced the mRNA expression of $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ at the highest dose. In addition, rutin treatment caused a significant reduction in COX-2 and iNOS mRNA levels compared to the control group. Conclusion: Overall, our results suggest that rutin has the potential to reduce inflammation, and that these effects are greater during tissue-damaging inflammatory conditions.

• Journal of Microbiology and Biotechnology
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• 제29권5호
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• pp.704-712
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• 2019

Although nanometric dead Lactobacillus plantarum has emerged as a potentially important modulator of immune responses, its underlying mechanism of action has not been fully understood. This study aimed to identify the detailed biochemical mechanism of immune modulation by micronized and heat-treated L. plantarum LM1004 (MHT-LM1004, <$1{\mu}m$ in size). MHT-LM1004 was prepared from L. plantarum LM1004 via culture in a specifically designed membrane bioreactor and heat treatment. MHT-LM1004 was shown to effectively induce the secretion of $TNF-{\alpha}$ and IL-6 and the mRNA expression of inducible nitric oxide synthase (iNOS). MHT-LM1004 enhanced the expression of TLR-2, phosphorylation of MAPKs (ERK), and nuclear translocation of $NF-{\kappa}B$ in a dose-dependent manner. Oral administration of MHT-LM1004 ($4{\times}10^9$ or $4{\times}10^{11}cells/kg$ mouse body weight) increased the splenocyte proliferation and serum cytokine levels. These results suggested that MHT-LM1004 effectively enhances early innate immunity by activating macrophages via the TLR-2/MAPK/$NF-{\kappa}B$ signalling pathway and that this pathway is one of the major routes in immune modulation by the Lactobacillus species.

• Clinics in Shoulder and Elbow
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• 제22권2호
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• pp.79-86
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• 2019

Background: Increased oxidative stress and inflammation play a critical role in the etiopathogenesis of chronic tendinopathy. Melatonin is an endogenous molecule that exhibits antioxidant and anti-inflammatory activity. The aim of this study was to evaluate the biochemical and histopathological effects of exogenous melatonin administrations in supraspinatus overuse tendinopathy. Methods: Fifty rats were divided into the following four groups: cage activity, melatonin treatment, corticosteriod therapy, and control. Melatonin (10 mg/kg, intraperitoneal; twice a day) and triamcinolone (0.3 mg/kg, subacromial; weekly) were administered to the treatment groups after the overuse period. Biochemical and histopathological evaluations were performed on serum samples and biopsies obtained from rats. Plasma inducible nitric oxide synthase (iNOS), vascular endothelial growth factor (VEGF), total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) levels were evaluated biochemically. Results: The TAS, TOS, OSI, iNOS, and VEGF values were significantly lower than the pre-treatment levels in rats receiving exogenous melatonin treatment (3 or 6 weeks) (p<0.05). TOS, iNOS, VEGF, and OSI values after 3 weeks of triamcinolone administration, and TOS, VEGF, and OSI levels after 6 weeks of triamcinolone application, were significantly lower than the pre-treatment levels (p<0.05). Conclusions: Exogenous melatonin application in overuse tendinopathy reduces oxidative stress and inflammation. Melatonin might be an alternative potential molecule to corticosteroids in the treatment of chronic tendinopathy.

• Journal of Ginseng Research
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• 제43권2호
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• pp.252-260
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• 2019

Background: Increases in the average global temperature cause heat stress-induced disorders by disrupting homeostasis. Excessive heat stress triggers an imbalance in the immune system; thus protection against heat stress is important to maintain immune homeostasis. Korean ginseng (Panax ginseng Meyer) has been used as a herbal medicine and displays beneficial biological properties. Methods: We investigated the protective effects of Korean ginseng extracts (KGEs) against heat stress in a rat model. Following acclimatization for 1 week, rats were housed at room temperature for 2 weeks and then exposed to heat stress ($40^{\circ}C$/2 h/day) for 4 weeks. Rats were treated with three KGEs from the beginning of the second week to the end of the experiment. Results: Heat stress dramatically increased secretion of inflammatory factors, and this was significantly reduced in the KGE-treated groups. Levels of inflammatory factors such as heat shock protein 70, interleukin 6, inducible nitric oxide synthase, and tumor necrosis factor-alpha were increased in the spleen and muscle upon heat stress. KGEs inhibited these increases by down-regulating heat shock protein 70 and the associated nuclear $factor-{\kappa}B$ and mitogen-activated protein kinase signaling pathways. Consequently, KGEs suppressed activation of T-cells and B-cells. Conclusion: KGEs suppress the immune response upon heat stress and decrease the production of inflammatory cytokines in muscle and spleen. We suggest that KGEs protect against heat stress by inhibiting inflammation and maintaining immune homeostasis.

• Journal of Ginseng Research
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• 제43권2호
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• pp.218-225
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• 2019

Background: Streptococcus pneumoniae, more than 90 serotypes of which exist, is recognized as an etiologic agent of pneumonia, meningitis, and sepsis associated with significant morbidity and mortality worldwide. Immunization with a pneumococcal pep27 mutant (${{\Delta}}pep27$) has been shown to confer comprehensive, long-term protection against even nontypeable strains. However, ${{\Delta}}pep27$ is effective as a vaccine only after at least three rounds of immunization. Therefore, treatments capable of enhancing the efficiency of ${{\Delta}}pep27$ immunization should be identified without delay. Panax ginseng Mayer has already been shown to have pharmacological and antioxidant effects. Here, the ability of Korean Red Ginseng (KRG) to enhance the efficacy of ${{\Delta}}pep27$ immunization was investigated. Methods: Mice were treated with KRG and immunized with ${{\Delta}}pep27$ before infection with the pathogenic S. pneumoniae strain D39. Total reactive oxygen species production was measured using lung homogenates, and inducible nitric oxide (NO) synthase and antiapoptotic protein expression was determined by immunoblotting. The phagocytic activity of peritoneal macrophages was also tested after KRG treatment. Results: Compared with the other treatments, KRG significantly increased survival rate after lethal challenge and resulted in faster bacterial clearance via increased phagocytosis. Moreover, KRG enhanced ${{\Delta}}pep27$ vaccine efficacy by inhibiting reactive oxygen species production, reducing extracellular signal-regulated kinase apoptosis signaling and inflammation. Conclusion: Taken together, our results suggest that KRG reduces the time required for immunization with the ${{\Delta}}pep27$ vaccine by enhancing its efficacy.

• 한국식품과학회지
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• 제53권2호
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• pp.115-120
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• 2021

Scutellaria baicalensis water extract (SWE)는 지질 다당류 LPS로 유도된 RAW 264.7 세포에서 NO 및 전 염증성 사이토카인인 TNF-α의 생성을 세포 독성을 유발하지 않고 유의하게 억제하였다. 또한, SWE는 iNOS 및 COX-2의 단백질발현을 농도의존적으로 감소시켰으며, ERK, JNK, p38과 같은 MAPKs 계열의 인산화 발현 수준을 조사한 결과 JNK와 p38의 발현 수준을 감소시켰다. 이는 SWE가 p38 인산화를 억제함으로써 iNOS, COX, 그리고 TNF-α와 같은 전 염증성 사이토카인의 발현을 감소시키며 결론적으로 NO의 생성을 억제시킨다는 결과를 도출할 수 있었다. 본 연구는 항염증 효능 검증뿐 아니라 염증대사기전의 주요인자를 탐색함으로써 황금의 기능성 소재로써의 가능성을 시사한다.

• Molecules and Cells
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• 제42권10호
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• pp.702-710
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• 2019

Neuroinflammation is an important contributor to the pathogenesis of neurodegenerative disorders including Parkinson's disease (PD). We previously reported that our novel synthetic compound KMS99220 has a good pharmacokinetic profile, enters the brain, exerts neuroprotective effect, and inhibits $NF{\kappa}B$ activation. To further assess the utility of KMS99220 as a potential therapeutic agent for PD, we tested whether KMS99220 exerts an anti-inflammatory effect in vivo and examined the molecular mechanism mediating this phenomenon. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice, oral administration of KMS99220 attenuated microglial activation and decreased the levels of inducible nitric oxide synthase and interleukin 1 beta ($IL-1{\beta}$) in the nigrostriatal system. In lipopolysaccharide (LPS)-challenged BV-2 microglial cells, KMS99220 suppressed the production and expression of $IL-1{\beta}$. In the activated microglia, KMS99220 reduced the phosphorylation of $I{\kappa}B$ kinase, c-Jun N-terminal kinase, and p38 MAP kinase; this effect was mediated by heme oxygenase-1 (HO-1), as both gene silencing and pharmacological inhibition of HO-1 abolished the effect of KMS99220. KMS99220 induced nuclear translocation of the transcription factor Nrf2 and expression of the Nrf2 target genes including HO-1. Together with our earlier findings, our current results show that KMS99220 may be a potential therapeutic agent for neuroinflammation-related neurodegenerative diseases such as PD.