• 대한본초학회지
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• 제31권6호
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• pp.37-44
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• 2016

Objective : This study aimed to evaluate the protective effect of Artemisiae Capillaris Herba (AC) in reflux esophagitis (RE) rats. Methods : The AC was measured antioxidant activity through in vitro experiments, such as total polyphenol and flavonoid contents, 1, 1-diphenyl-2-picrylhydrazyl (DPPH) and 2, 2'-azinobis-3-ethyl-benzothiazoline-6-sulfonic acid (ABTS) radical scavenging activity. Base on the results, we had conducted in vivo experiments. Rats were divided normal, control, AC treatment 50 mg/kg BW (AC50), and AC treatment 100 mg/kg BW (AC100) groups. AC were orally administered 2 h before the induction of RE. RE was induced by tie the pylorus and the transitional junction between the forestomach and the corpus in Sprague-Dawley rats. The rats were sacrificed 5 h after the surgery. We analyzed the expression of inflammatory related markers by western blot and observed the production of reactive oxygen species (ROS) and hematoxylin-eosin staining, Results : The $IC_{50}$ of AC for DPPH and ABTS were showed 12.60 and $33.32{\mu}g/m{\ell}$ respectively. In the RE rat, AC decreased inflammatory related markers, such as phosphorylated inhibitor of ${\kappa}B{\alpha}$, nuclear factor-kappa B, cyclooxygenase-2, inducible nitric oxide synthase, and tumor necrosis factor alpha. Also, AC reduced the increased reactive oxygen species in serum. The anti-inflammatory effect of AC appeared to be partially mediated through the inhibition of ROS. Also, AC markedly ameliorated esophageal mucosa damage via the inhibition of protein expression related to inflammation. Conclusions : Therefore, these results suggest that AC would be used as a therapeutic material in protection and/or treatment for reflux esophagitis.

• Journal of Applied Biological Chemistry
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• 제62권2호
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• pp.111-122
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• 2019

The mulberry tree (Morus alba L.) has been traditionally used in Chinese medicine to treat inflammatory diseases. We investigated the effects of bioconversion on different components of the mulberry tree, and determined changes in the physiological activities. Ethyl acetate-soluble fractions of five different segments (fruit, Mori Fructus; leaf, Mori Folium; twig, Mori Ramulus; root, Mori Cortex; and mistletoe, Loranthi Ramulus) of the mulberry tree show enhanced anti-oxidant effects in the 2,2-diphenyl-1-picrylhydrazyl, and 2,2'-azinobis-(3-ethylvenzothiazoline-6-sulfonic acid) assays, and enhanced anti-inflammatory effects of lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production in RAW 264.7 macrophages, after being treated with a crude enzyme extract from Aspergillus kawachii, in the following order of activity: Mori Folium>Mori Cortex>Mori Ramulus>Mori Fructus>Loranthi Ramulus. Ethyl acetate- soluble fraction of mulberry leaves (Mori Folium) that underwent bioconversion was most effective, and was devoid of any cytotoxicity. The fraction was also effective against mRNA expression of LPS-induced pro-inflammatory cytokines, such as inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis $factor-{\alpha}$, $interleukin-1{\beta}$, and interleukin-6. In addition, the fraction was effective in LPS-induced phosphorylation of mitogen-activated protein kinases and IKK, and $I{\kappa}B$ degradation, followed by translocation of the nuclear $factor-{\kappa}B$ from the cytoplasm to the nucleus. Thus, bioconversion increased the anti-oxidative and anti-inflammatory activities of the mulberry leaf.

• Journal of Ginseng Research
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• 제37권1호
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• pp.54-63
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• 2013

Ginsenoside Rd is a primary constituent of the ginseng rhizome and has been shown to participate in the regulation of diabetes and in tumor formation. Reports also show that ginsenoside Rd exerts anti-oxidative effects by activating anti-oxidant enzymes. Treatment with ginsenoside Rd decreased nitric oxide and prostaglandin $E_2$ ($PGE_2$) in lipopolysaccharides (LPS)-challenged RAW264.7 cells and in ICR mouse livers (5 mg/kg LPS; LPS + ginsenoside Rd [2, 10, and 50 mg/kg]). Furthermore, these decreases were associated with the down-regulations of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 and of nuclear factor (NF)-${\kappa}B$ activity in vitro and in vivo. Our results indicate that ginsenoside Rd treatment decreases; 1) nitric oxide production (40% inhibition); 2) $PGE_2$ synthesis (69% to 93% inhibition); 3) NF-${\kappa}B$ activity; and 4) the NF-${\kappa}B$-regulated expressions of iNOS and COX-2. Taken together, our results suggest that the anti-inflammatory effects of ginsenoside Rd are due to the down-regulation of NF-${\kappa}B$ and the consequent expressional suppressions of iNOS and COX-2.

• Journal of Ginseng Research
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• 제39권2호
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• pp.116-124
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• 2015

Background: Ginseng, the root of Panax ginseng (PG), is used widely as a herbal medicine to prevent and treat various diseases. Panax ginseng has pharmacological effects on neurodegenerative diseases such as Alzheimer's disease (AD). The present study evaluated the neuroprotective effects of PG and its possible neuroprotective mechanisms in advanced glycation end product (AGE)-induced AD in a rat model. Methods: Advanced glycation end products were injected bilaterally into the CA3 region of the rats' brains. The Morris water maze test and step-down type passive avoidance test were performed to evaluate their memory and cognitive abilities. The oxidation indexes in the hippocampus were detected. Immunohistochemistry was conducted to visualize the receptors for advanced glycation end products (RAGEs) and nuclear factor-kappa-light-chain-enhancer of activated B cell (NF-${\kappa}B$). Results: Behavioral results showed that PG (1 g/kg, 0.5 g/kg, and 0.25 g/kg) significantly shortened the escape latency, remarkably increased the number of crossing times, significantly decreased the number of errors, and prolonged the latency in rats with AGE-induced AD. Panax ginseng also significantly reduced the malondialdehyde level, increased the glutathione content, and increased superoxide dismutase activity in the hippocampus. Panax ginseng significantly decreased the expression of RAGE and NF-${\kappa}B$. The blockade of anti-RAGE antibody could significantly reduce AGE-induced impairments and regulate these expressions. Conclusion: Our results demonstrated that PG significantly inhibits AGE-induced memory impairment and attenuates Alzheimer-like pathophysiological changes. These neuroprotective effects of PG may be associated with the RAGE/NF-${\kappa}B$ pathway. Our results provided the experimental basis for applying PG in preventing and treating AD.

• Journal of Microbiology and Biotechnology
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• 제29권2호
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• pp.297-303
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• 2019

Corticosteroids are commonly used for pain control in rotator cuff tear. Deregulated $NF-{\kappa}B$ activation is a hallmark of chronic inflammatory diseases and has been responsible for the pathogenesis of rotator cuff tear. The Dexamethasone(DEXA) is a synthetic corticosteroid. The purpose of this study was to examine the exact effect of dexamethasone on $NF-{\kappa}B$ signaling in rotator cuff tear. We measured $NF-{\kappa}B$ expression in four groups: control, $TNF-{\alpha}$-treated, DEXA-treated, and combined treatment with $TNF-{\alpha}$ and DEXA. Tenocytes were isolated from patients with rotator cuff tears and pre-incubated with $TNF-{\alpha}$ (10 ng/ml), DEXA ($1{\mu}M$), or both of them for 10 min, 1 h, and 2 h. Expression of p65, p50, and p52 in the nuclei and cytosol was analyzed by western blotting and immunofluorescence imaging using confocal microscopy. We also evaluated nucleus/cytosol (N/C) ratios of p65, p50, and p52. In our study, the combined treatment with DEXA and $TNF-{\alpha}$ showed increased N/C ratios of p65, p50, and p52 compared with those in the $TNF-{\alpha}$ group at all time points. Additionally, in the DEXA group, N/C ratios of p65, p50, and p52 gradually increased from 10 min to 2 h. In conclusion, DEXA promoted the nuclear localization of p65, p50, and p52, but was not effective in inhibiting the inflammatory response of $TNF-{\alpha}$-stimulated rotator cuff tear.

• Journal of Ginseng Research
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• 제40권4호
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• pp.325-333
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• 2016

Background: Ginseng extracts are known to have angiogenic effects. However, to date, only limited information is available on the molecular mechanism underlying the angiogenic effects and the main components of ginseng that exert these effects. Human umbilical-vein endothelial cells (HUVECs) are used as an in vitro model for screening therapeutic agents that promote angiogenesis and wound healing. We recently isolated gintonin, a novel ginseng-derived lysophosphatidic acid (LPA) receptor ligand, from ginseng. LPA plays a key role in angiogenesis and wound healing. Methods: In the present study, we investigated the in vitro effects of gintonin on proliferation, migration, and tube formation of HUVECs, which express endogenous LPA1/3 receptors. Results: Gintonin stimulated proliferation and migration of HUVECs. The LPA1/3 receptor antagonist, Ki16425, short interfering RNA against LPA1 or LPA3 receptor, and the Rho kinase inhibitor, Y-27632, significantly decreased the gintonin-induced proliferation, migration, and tube formation of HUVECs, which indicates the involvement of LPA receptors and Rho kinase activation. Further, gintonin increased the release of vascular endothelial growth factors from HUVECs. The cyclooxygenase-2 inhibitor NS-398, nuclear factor kappa B inhibitor BAY11-7085, and c-Jun N-terminal kinase inhibitor SP600125 blocked the gintonin-induced migration, which shows the involvement of cyclooxygenase-2, nuclear factor kappa B, and c-Jun N-terminal kinase signaling. Conclusion: The gintonin-mediated proliferation, migration, and vascular-endothelial-growth-factor release in HUVECs via LPA-receptor activation may be one of in vitro mechanisms underlying ginsenginduced angiogenic and wound-healing effects.

• 한국미생물·생명공학회지
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• 제42권3호
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• pp.275-284
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• 2014

본 연구에서는 식물자원으로부터 생리활성을 보유한 새로운 기능성 소재를 찾고자 하였다. 이를 위해 수종의 중국 자생 식물을 분석하여 강한 항산화능을 보유한 3종(Malus hupehensis, Ophiorrhiza cantonensis, 그리고 Psychotria rubra)을 선별하고, 각 추출물의 항산화능과 항염증 생리활성을 분석하였다. 먼저 각 추출물의 항산화능을 DPPH radical 소거능을 통해 분석한 결과 모두 양성 대조군으로 사용한 ascorbic acid와 유사한 정도의 높은 활성을 보여 각 소재가 매우 강한 항산화능을 보유함을 확인하였다. 또한 RAW 264.7 세포주에서 $H_2O_2$ 및 LPS에 의해 유도된 ROS에 대한 각 추출물의 소거능을 분석한 결과에서도 농도의존적인 강한 소거능을 보였다. 뿐만 아니라 대표적인 항산화효소 중 하나로 항산화능 보유 천연물에 의해 발현이 유도되는 HO-1 및 그 전사 인자인 Nrf-2의 단백질 발현이 각 추출물의 처리에 의해 증가됨을 보였다. 한편 각 소재가 LPS에 의해 유도된 NO 생성에 미치는 영향을 분석한 결과 모두 농도의존적인 NO 생성 저해능을 보였으며 이는 NO 생성 단백질인 iNOS의 발현 저해에서 기인함을 확인하였다. 이와 같은 각 소재의 NO 생성 및 iNOS 발현 억제 효과는 염증 상위신호 전달계인 NF-${\kappa}B$ 및 AP-1의 조절을 통해 일어날 가능성을 보였다. 이러한 결과를 통해 중국 자생 식물 3종의 높은 항산화능과 항염증 활성을 처음으로 확인하였으며 향후 기능성 소재로서 유용하게 활용될 수 있을 것으로 판단된다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권6호
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• pp.2277-2281
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• 2015

Objectives: To explore the expression of astrocyte elevated gene-1 (AEG-1) in cervical cancer and analyze its correlation with microvascular density (MVD), nuclear factor kappaB (NF-kB p65) and vascular endothelial growth factor (VEGF). Materials and Methods: Immunohistochemical MaxVision method was adopted to detect the expression level of AEG-1, NF-kB p65 and VEGF in 45 samples of invading cervical cancer and 12 samples of cervicitis from The First Affiliated Hospital of Wenzhou Medical University. Tumor microvascular endothelial marker CD34 combined with Weidner was used to determine the MVD in cervical cancer tissue. The positive expression and staining conditions of AEG-1, NF-kB p65 and VEGF in cervical cancer tissues were observed under a light microscope. Correlations between expression of AEG-1 protein and those of NF-Kb p65 and VEGF, as well as MVD, were analyzed using Pearson correlation. Results: The expression levels of AEG-1 were $0.186{\pm}0.043$ in cervical cancer and $0.051{\pm}0.002$ in chronic cervicitis (p<0.01). Moreover, expression of AEG-1 was related to vascular invasion and lymphatic metastasis of cervical cancer (p<0.01), but not with age of the patients, differentiation degree, tumour size, pathological type and parametrial infiltration (p>0.05). Pearson correlation analysis showed that the expression of AEG-1 was linked with NF-kB p65 (r=0.501, p=0.000), VEGF (r=0.718, p=0.000) as well as MVD in cervical cancer tissue (r=0.815, p=0.000). Conclusions: AEG-1 is highly expressed in cervical cancer and promotes angiogenesis, which might be related to the fact that AEG-1 activating the signal pathway of NF-kB could up-regulate the level of VEGF expression.

• 생명과학회지
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• 제27권5호
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• pp.509-516
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• 2017

들깨(Perilla frutescents (L.) Britton var.) 새싹은 꿀풀과에 속하는 1년생 초본이다. 본 연구의 목적은 들깨 새싹 에탄올 추출물이 사이토카인으로 유도된 췌장 베타 세포 손상에 대한 예방 효과를 평가하기 위함이다. 췌장 소도 주위에 염증 세포 침습으로 의해 분비되는 사이토카인은 1형 당뇨병의 발병원인에 해당된다. 인터루킨-$1{\beta}$ (IL-$1{\beta}$), 인터페론-${\gamma}$ (IFN-${\gamma}$), 종양괴사인자-${\alpha}$ (TNF-${\alpha}$) 등의 사이토카인은 활성산소 형성을 유도한다. 세포 내 활성산소 축적은 췌장 베타 세포 기능장애와 세포사멸을 이끈다. 들깨 새싹 추출물은 항산화 효과를 증가 시켰으며 활성산소 생성을 억제하였다. 사이토카인은 세포생존율을 감소시켰고, iNOS와 COX-2의 발현을 증가시키고 산화질소 생성을 유도하였다. 들깨 새싹 추출물은 사이토카인으로 유도된 세포생존을 농도 의존적으로 예방하였다. 또한, 사이토카인에 의한 산화질소 생성과 iNOS와 COX-2의 단백질 발현 증가를 억제하였다. 더 나아가 들깨 새싹 추출물은 췌장 베타 세포주(RIN-m5F)에서 $I{\kappa}B{\alpha}$ 인산화 억제를 통해서 NF-${\kappa}B$의 활성화를 상당히 감소시켰다. 요약하자면, 본 연구 결과는 들깨 새싹 추출물이 사이토카인으로 유도된 췌장 베타 세포 손상에 대한 보호 효과를 가지고 있다는 것이 확인되었다. 결과적으로 들깨 새싹은 혈당 증가에 의한 산화 스트레스와 염증성 사이토카인에 의한 베타 세포 손상을 완화하여 당뇨에 유익할 것으로 사료된다.

• BMB Reports
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• 제53권2호
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• pp.106-111
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• 2020

Glutaredoxin 1 (GLRX1) has been recognized as an important regulator of redox signaling. Although GLRX1 plays an essential role in cell survival as an antioxidant protein, the function of GLRX1 protein in inflammatory response is still under investigation. Therefore, we wanted to know whether transduced PEP-1-GLRX1 protein inhibits lipopolysaccharide (LPS)- and 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced inflammation. In LPS-exposed Raw 264.7 cells, PEP-1-GLRX1 inhibited cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), activation of mitogen activated protein kinases (MAPKs) and nuclear factor-kappaB (NF-κB) expression levels. In a TPA-induced mouse-ear edema model, topically applied PEP-1-GLRX1 transduced into ear tissues and significantly ameliorated ear edema. Our data reveal that PEP-1-GLRX1 attenuates inflammation in vitro and in vivo, suggesting that PEP-1-GLRX1 may be a potential therapeutic protein for inflammatory diseases.