• Biomolecules & Therapeutics
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• 제21권5호
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• pp.398-404
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• 2013

During a screening program to search the anticolitic herbal medicines, 80% ethanol extract of the rhizome of Anemarrhena asphodeloides (AA) was found to potently inhibit the expression of proinflammatory cytokines TNF-${\alpha}$ and IL-1${\beta}$, as well as the activation of NF-${\kappa}B$ in LPS-stimulated colonic macrophages, followed by that of the rhizome of C. chinensis (CC). AA also potently inhibited TNBS-induced colitic markers, shortening of the colon and increase of macroscopic score, myeloperoxidase activity, TNF-${\alpha}$, IL-1${\beta}$, and IL-6, in mice. The synergistic effect of CC against the anticolitic effect of AA was investigated. CC synergistically inhibited the anticolitic effect of AA. AC-mix (AA+CC, 1:1) potently inhibited them. AC-mix also inhibited the activation of NF-${\kappa}B$, as well as the expression of TNF-${\alpha}$, IL-1${\beta}$, IL-6, iNOS and COX-2. The effects of AC-mix against oxazolone-induced colitis were investigated in mice. AC-mix also potently inhibited oxazolone-induced inflammatory markers, colon shortening, macroscopic score, myeloperoxidase activity, NF-${\kappa}B$ activation and proinflammatory cytokines. Overall, the anti-colitic effect of AC-mix was superior to that of mesalazine. Based on these findings, AC-mix may improve colitis by inhibiting NF-${\kappa}B$ activation.

• Biomolecules & Therapeutics
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• 제24권5호
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• pp.543-551
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• 2016

This study was designed to evaluate the pharmacological effects of Vaccinium bracteatum Thunb. methanol extract (VBME) on microglial activation and to identify the underlying mechanisms of action of these effects. The anti-inflammatory properties of VBME were studied using lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. We measured the production of nitric oxide (NO), inducible NO synthase (iNOS), cyclooxygenase (COX)-2, prostaglandin $E_2$ ($PGE_2$), tumor necrosis factor-alpha (TNF-${\alpha}$), interleukin-1 beta (IL-$1{\beta}$), and interleukin-6 (IL-6) as inflammatory parameters. We also examined the effect of VBME on intracellular reactive oxygen species (ROS) production and the activity of nuclear factor-kappa B p65 (NF-${\kappa}B$ p65). VBME significantly inhibited LPS-induced production of NO and $PGE_2$ and LPS-mediated upregulation of iNOS and COX-2 expression in a dose-dependent manner; importantly, VBME was not cytotoxic. VBME also significantly reduced the generation of the pro-inflammatory cytokines TNF-${\alpha}$, IL-$1{\beta}$, and IL-6. In addition, VBME significantly dampened intracellular ROS production and suppressed NF-${\kappa}B$ p65 translocation by blocking $I{\kappa}B-{\alpha}$ phosphorylation and degradation in LPS-stimulated BV2 cells. Our findings indicate that VBME inhibits the production of inflammatory mediators in BV-2 microglial cells by suppressing NF-${\kappa}B$ signaling. Thus, VBME may be useful in the treatment of neurodegenerative diseases due to its ability to inhibit inflammatory mediator production in activated BV-2 microglial cells.

• 한방안이비인후피부과학회지
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• 제22권3호
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• pp.63-70
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• 2009

Objectives : The present study was examined to evaluate the anti-inflammatory effects of the Gentianae Macrophyllae Radix MeOH extracts (GMR) in vivo. Methods : The effects of GMR on anti-inflammation were measured by production of NO, TNF-$\alpha$ (Tumor Necrosis Factor-alpha) and IL-$1{\beta}$ (Interleukin-$1{\beta}$), IL-6 in Raw 264.7 macrophage cells stimulated with LPS. Results : 1. All concentrations of GMR(0.10 mg/ml) had no significant cytotoxicity in Raw 264.7 cell during the entire experimental period. 2. The level of NO and iNOS in culture medium was dramatically increased by LPS application. However, these increases were dose-dependently(0.03 and 0.10 mg/ml) attenuated by treatment with GMR. 3. All concentrations of GMR significantly inhibited the production of IL-$1{\beta}$ in Raw 264.7 macrophage cells stimulated with LPS. Conclusions : These results provide evidences that therapeutic effect of GMR on heat syndrome, especially due to the acute inflammation, are partly due to the reduction of some of inflammatory factors by inhibiting iNOS and COX-2 through the suppression of $p-I{\kappa}B{\alpha}$. Moreover, it suggests that the mechanism of action of GMR comes from the suppression of inflammatory mediators, such as NO, PGE2 and pro-inflammatory cytokines.

• 대한한방소아과학회지
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• 제28권3호
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• pp.47-58
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• 2014

Objectives GyejigaChulBuTang (GCBT) is a prescription used to treat acute and chronic arthritis in Korea, China, and Japan. This study assessed the anti-inflammatory and anti-oxidant activities of GCBT on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. Methods Raw264.7 cells were pretreated with or without GCBT for 1 hour prior to incubation with LPS. Anti-inflammatory activity of GCBT was evaluated with reference to gene expression and production levels of proinflammatory cytokines ($TNF{\alpha}$, IL-$1{\beta}$, IL-6, GM-CSF and $INF{\gamma}$) and inflammatory mediators (iNOS, COX-2, NO and $PGE_2$). In addition, intracellular ROS generation and signal transduction of MAPK family, PI3K/Akt and $I{\kappa}B{\alpha}/NF{\kappa}B$ was investigated. Results Prior treatment with GCBT inhibited elevation of $TNF{\alpha}$, IL-$1{\beta}$, IL-6, GM-CSF, $INF{\gamma}$, NO and $PGE_2$, together with their cognate mRNAs in a dose-dependent manner. Intracellular ROS contents were similarly reduced. These effects were due to inhibition of LPS-induced phosphorylation of MAPK family, PI3K/Akt and $I{\kappa}B{\alpha}$ as well as nuclear translocation of $NF{\kappa}B$. Conclusions GCBT suppresses pro-inflammatory mediators. GCBT has potential in the treatment of juvenile rheumatoid arthritis associated with inflammation.

• Nutrition Research and Practice
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• 제13권3호
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• pp.189-195
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• 2019

BACKGROUND/OBJECTIVES: Although aged black garlic has various biological activities such as anti-allergy, anti-inflammation and neuroprotection, effect of aged black garlic on chemically contact dermatitis is unclarified. MATERIALS/METHODS: To evaluate anti-dermatitic activity of aged black garlic extract, we investigated effects of a fraction of aged black garlic extract (BG10) on both in vivo and in vitro. RESULTS: BG10 almost inhibited formation of nitric monoxide and interleukin-6 (IL-6; $IC_{50}$, $7.07{\mu}g/mL$) at $25{\mu}g/mL$, and dose-dependently reduced production of tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$; $IC_{50}$, $52.07{\mu}g/mL$) and prostaglandin $E_2$ ($IC_{50}$, $38.46{\mu}g/mL$) in lipopolysaccharide-stimulated RAW264.7 cells. In addition, BG10 significantly inhibited the expression of inducible nitric oxide synthase, cyclooxygenase-2 and nuclear $NF-{\kappa}B$, and improved that of cytosolic levels of $NF-{\kappa}B$ and $I{\kappa}B{\alpha}$ in the cells. Consistent with in vitro studies, BG10 (0.5 mg/mL) not only reduced ear edema but also suppressed the formation of IL-6 and $TNF-{\alpha}$ induced by 12-O-tetradecanoylphorbol-13-acetate in ear tissues of mice. CONCLUSIONS: These findings suggest BG10 has anti-dermatitic activity through inhibiting activation of macrophages. Therefore, such effects of BG10 may provide information for the application of aged black garlic for prevention and therapy of contact dermatitis.

• 공업화학
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• 제30권2호
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• pp.145-150
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• 2019

본 연구에서는 우슬(Achyranthes japonica, AJ)과 Lactobacillus plantarum으로 발효한 우슬(AJ-LP)을 5가지 용매(물, 에탄올, 헥산, 아세트산에틸, 부탄올)로 추출하여 RAW264.7 세포에서 항염증 활성에 미치는 영향을 확인하였다. lipopolysaccharide(LPS)로 유도된 RAW264.7 세포에서 nitric oxide (NO) 및 cytokine 생성을 측정하였으며 western blot으로 cyclooxygenase-2(COX-2)와 nitric oxide synthase (iNOS)의 발현 정도를 관찰하였다. 세포 독성은 CCK assay를 통해 확인하였으며 독성을 가지지 않는 농도인 $100{\mu}g/mL$로 실험을 진행하였다. NO 생성 저해 활성 결과 AJ-LP를 에탄올(E)로 추출한 시료가 LPS만 처리한 control군에 비해 약 74%로 저해율이 가장 높았으며 염증관련 cytokine인 Interleukin-6 (IL-6), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), and Interleukin-$1{\beta}$ (IL-$1{\beta}$)의 결과에서도 약 57, 70, 74%의 저해율로 우수한 효능을 보였다. COX-2와 iNOS 발현결과 AJ군에서 대조군(20-hydroxyecdysone)의 저해율이 가장 높은 것으로 나타났다. AJ-LP군에서 COX-2 발현량은 헥산(H)으로 추출한 시료가 대조군에 비해 약 16%로 감소하였고 iNOS 발현량은 부탄올(B)으로 추출한 시료가 약 7%로 감소하였다. 이상의 결과들에서 우슬보다 L. plantarum으로 발효한 우슬이 천연물 소재로서의 활용 가능성이 높음을 시사하였다.

• 한방안이비인후피부과학회지
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• 제18권1호
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• pp.183-198
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• 2005

This experimental study was performed to investigate the anti-inflammatory effects of Phellodendri Cortex(PC), Indigo Naturalis(IN). Alumen(AM), and Chinensis Galla(CG). These four prescriptions most frequently have been used in of oriental medicine for the external the theraphy of Gu-Chang. This study was done to evaluate the activity of superoxide dismutase(SOD) and the inhibitory effects of the formation of cyclooxygenase-2(COX-2), tumor necrosis $factor-{\alpha}(TNF-{\alpha}),\;interlenkin-1{\beta}(IL-1{\beta})$, prostaglandin-E2(PGE2) on the monocyte and neutrophil. The results were summerized as follows. 1. IN has no cytotoxicity but PC, AM, CG have a little cytotoxicity by the increase of concentrations. 2. PC, IN, AM and CG all inhibited the formation of COX-2 in the human neutrophil. 3. $1000{\mu}g/m{\ell}$ of PC increased the formation of SOD in the human monocyte. 4. $1000{\mu}g/m{\ell}$ of PC, $100{\mu}g/m{\ell}$ and $1000{\mu}g/m{\ell}$ of IN, $100{\mu}g/m{\ell}$ of CG inhibited the formation of $TNF-{\alpha}$ in the human monocyte. 5. $10{\mu}g/m{\ell}$ of PC, $1000{\mu}g/m{\ell}$ of IN inhibited the formation of $IL-1\;{\beta}$ in the human monocyte. 6. PC, IN, AM and CG all did not inhibit the production of PGE2 in the human monocyte In addition, the results show that PC, IN, AM and CG all have anti-inflammatory effects and can be used fer the external theraphy of Cu-Chang.

• 동의신경정신과학회지
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• 제22권2호
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• pp.107-128
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• 2011

Objectives : This experiment was designed to investigate the efficacy of DDTCMT hot water extract & ultra-fine powder on Alzheimer's Disease Model. Methods : The effects of the DDTCMT hot water extract on expression of IL-$1{\beta}$, IL-6, TNF-${\alpha}$, COX-2, NOS-II, IL-10, IL-1 receptor antagonist mRNA and production of IL-$1{\beta}$, IL-6, TNF-${\alpha}$ in BV2 microglial cell line treated by lipopolysacchaide(LPS) were investigated. Expression of NO, ROS in BV2 microglial cell line treated by LPS and AChE activity in PC-12 cell treated by NGF were investigated. anti-AChE was observed through Western blot analysis. The effects of the DDTCMT hot water extract & ultra-fine powder on the behavior of the memory deficit mice induced by scopolamine were investigated. Results : 1. The DDTCMT hot water extract significantly decreased the production of mIL-6, mNOS-II, mTNF-${\alpha}$, and increased the production of mIL-10, mIL-1 receptor antagonist. 2. The DDTCMT hot water extract significantly suppressed the production of IL-$1{\beta}$, IL-6, TNF-${\alpha}$ in BV2 microglial cell line treated by LPS. 3. The DDTCMT hot water extract significantly suppressed the NO and ROS production in BV2 microglial cell line treated by LPS. 4. The DDTCMT hot water extract groups showed inhibition of AChE activity in NGF treated PC-12 cell line. 5. The DDTCMT hot water extract suppressed anti-AChE expression in NGF treated PC-12 cell line was observed by Western blot analysis. 6. The DDTCMT hot water extract & ultra-fine powder groups showed significantly inhibitory effect on the scopolamine -induced impairment of memory in the experiment of Morris water maze. Conclusions : These results suggest that the DDTCMT hot water extract & ultra-fine powder may be effective for the prevention and treatment of Alzheimer's disease.

• Natural Product Sciences
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• 제21권4호
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• pp.240-247
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• 2015

Viridicatol (1) has previously been isolated from the extract of the marine-derived fungus Penicillium sp. SF-5295. In the course of further biological evaluation of this quinolone alkaloid, anti-inflammatory effect of 1 in RAW264.7 and BV2 cells stimulated with lipopolysaccharide (LPS) was observed. In this study, our data indicated that 1 suppressed the expression of well-known pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, and consequently inhibited the production of iNOS-derived nitric oxide (NO) and COX-2-derived prostaglandin E2 ($PGE_2$) in LPS stimulated RAW264.7 and BV2 cells. Compound 1 also reduced mRNA expression of pro-inflammatory cytokines such as $interleukin-1{\beta}$ ($IL-1{\beta}$), interleukin-6 (IL-6), and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$). In the further evaluation of the mechanisms of these anti-inflammatory effects, 1 was shown to inhibit nuclear factor-kappa B ($NF-{\kappa}B$) pathway in LPS-stimulated RAW264.7 and BV2 cells. Compound 1 blocked the phosphorylation and degradation of inhibitor kappa B $(I{\kappa}B)-{\alpha}$ in the cytoplasm, and suppressed the translocation of $NF-{\kappa}B$ p65 and p50 heterodimer in nucleus. In addition, viridicatol (1) attenuated the DNA-binding activity of $NF-{\kappa}B$ in LPS-stimulated RAW264.7 and BV2 cells.

• 한국자원식물학회지
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• 제28권2호
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• pp.145-152
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• 2015

본 연구에서는 까마귀쪽나무 잎과 열매 추출물의 항염증 활성을 비교하고자 마우스 대식세포주인 RAW 264.7 cell에서 LPS에 의해 유도된 COX-2/PGE2와 iNOS/NO 및 염증성 cytokine 인 TNF-${\alpha}$, IL-$1{\beta}$, IL-6의 생성 억제 정도를 확인하였다. 그 결과, 동일한 농도 조건($10{\mu}g/ml$)에서 까마귀쪽나무의 열매 추출물이 잎 추출물에 비해 NO, $PGE_2$, iNOS, 염증성 cytokine인 TNF-${\alpha}$, IL-$1{\beta}$, IL-6의 생성량 모두에서 억제 효능이 우수하게 나타났다. 따라서 까마귀쪽나무가 보여주는 항염증 효과적 측면과 안전성의 두가지 측면을 고려할 때, 까마귀쪽나무의 열매 추출물이 저농도에서 잎 추출물보다 항염증 효과가 우수하거나 동등하며, 그 안전성이 크다고 판단됨으로 까마귀쪽나무의 열매추출물이 항염증 효능을 가진 기능성 식품 소재로써 개발 가능성이 있음을 제시한다.