• Journal of Ginseng Research
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• 제43권1호
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• pp.10-19
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• 2019

Background: Frequent overdose of paracetamol (APAP) has become the major cause of acute liver injury. The present study was designed to evaluate the potential protective effects of ginsenoside Rk1 on APAP-induced hepatotoxicity and investigate the underlying mechanisms for the first time. Methods: Mice were treated with Rk1 (10 mg/kg or 20 mg/kg) by oral gavage once per d for 7 d. On the 7th d, allmice treated with 250mg/kg APAP exhibited severeliverinjury after 24 h, and hepatotoxicitywas assessed. Results: Our results showed that pretreatment with Rk1 significantly decreased the levels of serum alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor, and interleukin-$1{\beta}$ compared with the APAP group. Meanwhile, hepatic antioxidants, including superoxide dismutase and glutathione, were elevated compared with the APAP group. In contrast, a significant decrease in levels of the lipid peroxidation product malondialdehyde was observed in the ginsenoside Rk1-treated group compared with the APAP group. These effects were associated with a significant increase of cytochrome P450 E1 and 4-hydroxynonenal levels in liver tissues. Moreover, ginsenoside Rk1 supplementation suppressed activation of apoptotic pathways by increasing Bcl-2 and decreasing Bax protein expression levels, which was shown using western blotting analysis. Histopathological observation also revealed that ginsenoside Rk1 pretreatment significantly reversed APAP-induced necrosis and inflammatory infiltration in liver tissues. Biological indicators of nitrative stress, such as 3-nitrotyrosine, were also inhibited after pretreatment with Rk1 compared with the APAP group. Conclusion: The results clearly suggest that the underlying molecular mechanisms in the hepatoprotection of ginsenoside Rk1 in APAP-induced hepatotoxicity may be due to its antioxidation, antiapoptosis, anti-inflammation, and antinitrative effects.

• 생약학회지
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• 제53권4호
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• pp.192-201
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• 2022

This study aimed to compare bioactivities of Centella asiatica (CA) cultivated in smart farms and fields. Component analysis, cell viability, anti-inflammatory activity, neuroprotection activity, and antioxidant activity were examined with 70% ethanol extracts of CA cultivated in smart farm (SEE) and field (FEE), respectively. Asiaticoside was analyzed by high performance liquid chromatography (HPLC) and as a result, SEE had more asiaticoside content than FEE. After treatment of RAW 264.7 cells with SEE and FEE, there was no cytotoxicity within the treated concentrations. SEE and FEE showed nitric oxide (NO), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 inhibitory activities in a dose-dependent manner in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Moreover, SEE inhibited more NO, TNF-α, and IL-6 production levels than FEE. SEE and FEE reversed the H₂O₂-induced SH-SY5Y cell death. Especially, SEE was more effective in changing the H₂O₂-induced SH-SY5Y cell death than FEE. The antioxidant activity was confirmed by various methods such as total phenol content (TPC), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and superoxide dismutase (SOD). As a result, SEE showed the most potent antioxidant activities about TPC, DPPH, and SOD methods. This study suggested that SEE has higher bioactivities such as effect of anti-inflammation, neuroprotection, and antioxidation than FEE.

• Physical Therapy Rehabilitation Science
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• 제2권1호
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• pp.21-26
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• 2013

Objective: The aim of this study was to investigate the effect of therapeutic ultrasound (US) of cell viability and inflammatory cytokine in rat articular chondrocyte cultures stimulated with lipopolysaccharide (LPS). Design: One group pretest-posttest design. Methods: Cultured chondrocytes were treated with US and/or LPS and assessed for viability, Tumor necrosis factor $(TNF)-{\alpha}$ and Interleukin (IL)-1 production. Results: Oxidative stress was induced in rat chondrocytes with LPS. The cell viability was decreased in chondrocytes after treatment with LPS. The viability revealed that low-intensity pulsed ultrasound (LIPUS) exerted no significant cytotoxicity in the rat chondrocyte. LIPUS inhibited decreased cell viability in the presence of LPS ($30{\mu}g/ml$) in a intensity dependent pattern at LIPUS (p<0.05). $TNF-{\alpha}$ production in the presence of LPS was also inhibited in a dose dependent manner (p<0.05 from $30mW/cm^2$). IL-1 production in the presence of LPS was inhibited as well (p<0.05 from $7.5mW/cm^2$). Conclusions: Our results demonstrate that US was the anti-inflammatory effect of chondrocytes. LIPUS may exert its anti inflammatory effects through inhibition of $TNF-{\alpha}$ and IL-1 synthesis. These results suggest that US have potential for use as a pain relief and reduce the articular destruction.

• 동의생리병리학회지
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• 제17권4호
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• pp.1065-1074
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• 2003

In order to evaluate the antiallergic effects of Kamiyukgunja-tang (KYGJT), studies were done. We measured the cytotoxic activity for lung fibroblast cell, cytokines transcript expression, production of INF-γ, IL-10, IL-4, GM-CSF, IL-1 β, TNF-α. IL-5 proliferation of B cell in anti-CD40mAb plus r1L-4 stimulated murine splenic B cells. The results were obtained as follows : 1. KYGJT was not showed cytotoxicity in the fibroblast lung cell. 2. KYGJT increased the gene synthesis of INF-γ, IL-10, GM-CSF(m-RNA). 3. KYGJT decreased the gene synthesis of IL-1β, IL-4, TNF-α, IL-5(m-RNA). 4. KYGJT decreased the appearance of TNF-α significantly. 5. KYGJT decreased the appearance of IgE significantly. 6. KYGJT decreased the proliferation of B cell significantly. 7. KYGJT decreased the appearance of Histamin Release Production significantly. The facts above prove that KYGJT is effective against the allergy. Thus. I think that we should study on this continuously

• International Journal of Molecular Medicine
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• 제44권5호
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• pp.1741-1752
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• 2019

In the present study, a polyphenolic mixture was isolated from Seomae mugwort (SM; a native Korean variety of Artemisia argyi H.) via extraction with aqueous 70% methanol followed by the elution of ethyl acetate over a silica gel column. Each polyphenolic compound was analyzed using high-performance liquid chromatography coupled with tandem mass spectrometry, and compared with the literature. In addition to the 14 characterized components, one hydroxycinnamate, six flavonoids, and one lignan were reported for the first time, to the best our knowledge, in Artemisia argyi H. The anti-inflammatory properties of SM polyphenols were studied in lipopolysaccharide-treated RAW 264.7 macrophage cells. The SM polyphenols attenuated the activation of macrophages via the inhibition of nitric oxide production, nuclear factor-κB activation, the mRNA expression of inducible nitric oxide synthase, tumor necrosis factor α and interleukin-1β, and the phosphorylation of mitogen-activated protein kinase. Our results suggested that SM polyphenols may have therapeutic potential for the treatment of inflammatory-related diseases.

• 한국식품영양과학회지
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• 제43권10호
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• pp.1527-1534
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• 2014

Lactobacillus rhamnosus로 발효시킨 흑마늘 발효물의 항염증 효능을 검증하기 위해 LPS로 염증 유도된 RAW 264.7 cells를 이용하여 관련 인자들을 분석하였다. 100, 200, 400 및 $800{\mu}g/mL$ 농도에서 세포독성은 유발되지 않았으며, 오히려 농도 의존적으로 세포 생존율은 증가하였다. LPS에 의해 염증 유도된 RAW 264.7 cells에서 흑마늘 발효물은 농도 의존적으로 NO와 $PGE_2$의 생성 감소와 염증성 사이토카인인 TNF-${\alpha}$, IL-$1{\beta}$ 및 IL-6의 단백질 생성을 감소시켰다. 또한 iNOS, COX-2, NF-${\kappa}B$ 및 $I{\kappa}B$ 단백질의 발현을 감소시키고 HO-1의 단백질의 발현을 증가시켰다. 이상의 연구 결과를 통해 흑마늘 발효물은 염증에 의한 NF-${\kappa}B$의 활성과 TNF-${\alpha}$, IL-$1{\beta}$와 IL-6의 생성을 억제시키고, iNOS 및 COX-2의 발현을 억제시키는 메커니즘을 통해 염증성 질환의 예방 및 개선 효능을 나타내는 것으로 판단된다.

• 한국식품영양과학회지
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• 제41권9호
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• pp.1226-1234
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• 2012

본 연구에서는 염증반응을 조절하는 다양한 신호전달체계를 중심으로 분자생물학적 방법을 통해 piceatannol의 항염증 기전을 규명하였다. LPS로 염증반응을 유도한 Raw 264.7 대식세포에서 piceatannol은 iNOS의 발현 억제를 통해 NO의 생성을 감소시키고 염증성 사이토카인(TNF-${\alpha}$, IL-6, IL-$1{\beta}$)의 생성을 감소시켰다. 염증반응을 조절하는 신호전달체계 중 piceatannol은 LPS에 의해 유도된 $I{\kappa}B$의 분해와 p65의 핵으로의 이동을 억제하고, LPS에 의해 유도된 SAPK/JNK의 인산화를 억제하였다. 또한 piceatannol은 LPS와 IL-6(LPS에 의해 증가됨)에 의한 STAT3의 활성화를 억제하였다. 뿐만 아니라 piceatannol은 Nrf2의 핵 내 축적을 야기하고 ARE의 transcriptional activity를 증가시켜 HO-1의 발현을 증가시켰다. 본 연구의 결과, piceatannol은 NF-${\kappa}B$와 AP-1, STAT3 신호전달의 억제를 통해, 그리고 HO-1의 발현 증가를 통해 항염증 효과를 나타내었다(Fig. 8).

• 한국식품영양과학회지
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• 제45권2호
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• pp.181-187
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• 2016

본 연구에서는 홍조류인 꽃지누아리 에탄올 추출물(GIHEE)의 항염증 활성을 확인하기 위해 LPS로 활성화된 RAW 264.7 세포로부터 분비되는 염증매개성 물질들의 발현량 억제를 관찰하여 추출물의 항염증 활성을 탐색하고자 하였다. 그 결과 GIHEE 50 및 $100{\mu}g/mL$ 농도 처리 시 LPS로 유도된 염증반응에서 NF-${\kappa}B$ 활성 억제와 더불어 MAPKs의 인산화를 효과적으로 억제함을 보였다. 염증반응 매개인자들인 NO 및 염증성 사이토카인의 생성도 효과적으로 제어함을 보였으며, 특히 GIHEE $50{\mu}g/mL$ 농도에서 TNF-${\alpha}$ 및 IL-$1{\beta}$ 분비량은 각각 약 51% 및 30% 이상, IL-6 분비량은 $100{\mu}g/mL$에서 약 54% 이상의 높은 분비량 감소를 나타내었다. 따라서 GIHEE는 이들 염증매개성 물질들의 활성을 효과적으로 억제함으로써 항염증 활성을 나타내었으며, 염증성 질병의 예방 및 치료에 효과적인 기능성 소재로의 가능성이 충분하다고 사료된다.

• The Korean Journal of Physiology and Pharmacology
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• 제24권4호
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• pp.363-372
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• 2020

Gardenia jasminoides (GJ) is a widely used herbal medicine with anti-inflammatory properties, but its effects on the ORAI1 channel, which is important in generating intracellular calcium signaling for T cell activation, remain unknown. In this study, we investigated whether 70% ethanolic GJ extract (GJ_EtOH) and its subsequent fractions inhibit ORAI1 and determined which constituents contributed to this effect. Whole-cell patch clamp analysis revealed that GJ_EtOH (64.7% ± 3.83% inhibition at 0.1 mg/ml) and all its fractions showed inhibitory effects on the ORAI1 channel. Among the GJ fractions, the hexane fraction (GJ_HEX, 66.8% ± 9.95% at 0.1 mg/ml) had the most potent inhibitory effects in hORAI1-hSTIM1 co-transfected HEK293T cells. Chemical constituent analysis revealed that the strong ORAI1 inhibitory effect of GJ_HEX was due to linoleic acid, and in other fractions, we found that genipin inhibited ORAI1. Genipin significantly inhibited I_ORAI1 and interleukin-2 production in CD3/CD28-stimulated Jurkat T lymphocytes by 35.9% ± 3.02% and 54.7% ± 1.32% at 30 μM, respectively. Furthermore, the same genipin concentration inhibited the proliferation of human primary CD4⁺ T lymphocytes stimulated with CD3/CD28 antibodies by 54.9% ± 8.22%, as evaluated by carboxyfluorescein succinimidyl ester assay. Our findings suggest that genipin may be one of the active components of GJ responsible for T cell suppression, which is partially mediated by activation of the ORAI1 channel. This study helps us understand the mechanisms of GJ in the treatment of inflammatory diseases.

• 셀메드
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• 제4권4호
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• pp.28.1-28.27
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• 2014

Linderae Radix, the dry roots of Lindera aggregata (Sims) Kosterm, has long been used as traditional Chinese medicine for treatment of inflammatory diseases. The total alkaloids are believed to be the active components responsible for anti-inflammation of Linderae Radix. Here, the total alkaloids of Linderae Radix were extracted and isolated, including 12 isoquinoline alkaloids and 1 furan sesquiterpene. Within the alkaloids, norisoboldine, boldine, linderaline, isoboldine, reticuline, N-methyllaurotetanine, norjuziphine were found to be the major ingredients. In lipopolysaccharide-treated macrophage RAW 264.7 cells, application of Linderae Radix extract, or total alkaloids, suppressed the transcription of proinflammatory cytokines, interleukin-$1{\beta}$ and interleukin-6. Out of the 12 alkaloids, norisoboldine, boldine, and isoboldine were tested in lipopolysaccharide-treated macrophages, and norisoboldine was the strongest alkaloid in suppressing the cytokine expressions. The current studies suggested that the identification of alkaloids from Linderae Radix could provide a plausible explanation for herbal therapeutic functions.