• Journal of Nutrition and Health
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• 제55권1호
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• pp.59-69
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• 2022

본 연구실의 선행 연구에서 항산화 활성이 가장 높았던 조팝나무 H₂O-EtOH (40:60) 분획물(SP60)의 항염 효능을 확인하여 기능성 소재로의 개발 가능성을 알아보고자 하였다. 항염활성 측정을 위해 RAW 264.7 세포에서 먼저 WST assay를 실시하여 SP60이 125 ㎍/mL 농도까지 세포 생존율에 영향을 미치지 않는 것을 확인하였다. Raw264.7 세포에 LPS와 SP60을 동시에 처리하여 NO, TNF-α, IL-6, IL-1β 생성과 iNOS, COX-2, NF-κB 발현을 측정하였다. SP60은 NO, TNF-α, IL-6, IL-1β 생성량을 모두 유의하게 억제시켰으며 western blot으로 iNOS, COX-2의 발현과 NF-κB의 활성을 측정한 결과 SP60을 처리한 군에서 농도 의존적으로 그 발현량과 활성을 억제하였다. 따라서 조팝나무 분획물은 항염 효능을 가진 것으로 판단되며 항염 관련 기능성 식품 및 소재로의 개발 가능성을 확인하였다.

• Journal of Ginseng Research
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• 제46권6호
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• pp.738-749
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• 2022

Background: Ginseng possesses antitumor effects, and ginsenosides are considered to be one of its main active chemical components. Ginsenosides can further be hydrolyzed to generate secondary saponins, and 20(R)-panaxotriol is an important sapogenin of ginsenosides. We aimed to synthesize a new ginsengenin derivative from 20(R)-panaxotriol and investigate its antitumor activity in vivo and in vitro. Methods: Here, 20(R)-panaxotriol was selected as a precursor and was modified into its derivatives. The new products were characterized by ¹H-NMR, ¹³C-NMR and HR-MS and evaluated by molecular docking, MTT, luciferase reporter assay, western blotting, immunofluorescent staining, colony formation assay, EdU labeling and immunofluorescence, apoptosis assay, cells migration assay, transwell assay and in vivo antitumor activity assay. Results: The derivative with the best antitumor activity was identified as 6,12-dihydroxy-4,4,8,10,14-pentamethyl-17-(2,6,6-trimethyltetrahydro-2H-pyran-2-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl(tert-butoxycarbonyl)glycinate (A11). The focus of this research was on the antitumor activity of the derivatives. The efficacy of the derivative A11 (IC₅₀ < 0.3 µM) was more than 100 times higher than that of 20(R)- panaxotriol (IC₅₀ > 30 µM). In addition, A11 inhibited the protein expression and nuclear accumulation of the hypoxia-inducible factor HIF-1α in HeLa cells under hypoxic conditions in a dose-dependent manner. Moreover, A11 dose-dependently inhibited the proliferation, migration, and invasion of HeLa cells, while promoting their apoptosis. Notably, the inhibition by A11 was more significant than that by 20(R)-panaxotriol (p < 0.01) in vivo. Conclusion: To our knowledge, this is the first study to report the production of derivative A11 from 20(R)-panaxotriol and its superior antitumor activity compared to its precursor. Moreover, derivative A11 can be used to further study and develop novel antitumor drugs.

• Nuclear Engineering and Technology
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• 제25권4호
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• pp.529-538
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• 1993

이전에 제신된 시간 균일적인 경우의 모델［1］에 대한 확장으로 균열암반내 핵종이동에 관한 연속시간 마코프 프로세스를 이용한 통계적 방법에 의한 모델이 제시되었다. 단일 평판 균일을 갖는 암반매질에서 핵종이 균열로부터 알반조직내로 확산 이동하는 경우 더 이상 균열시간적인 마코프 모델을 적용할 수 없으므로 암반으로의 확산항을 시간에 따라 변화하는 과정으로 보아 모델을 제시한 후 기존의 결정론적 해석해와 비교하였다. 통계적모델의 최종 결과는 시간의 함수로서의 상태변수에 대한 기댓값과 그 분산치일 것이다. 핵종의 시간 종속적인 확률분포가 전이강도가 주어질 때 매질내의 특성이 균질하다고 볼 수 있도록 나누어진 암반매질의 각 구획에 대해 주어지게 된다. 이 모델은 매질공간에 대해 불연속적이므로 핵종이동에 영향을 주는 변수들이 쉽게 균열암반이나 다중매질 등과 같은 비균질한 매질에 적용되어 질수 있다. 매질을 나눈 구획수가 수치적 분산에 민감한 것으로 나타났지만 분산계수의 보정에 의해 해석해와 잘 일치되는 것을 알 수 있었다.

• 생명과학회지
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• 제19권5호
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• pp.633-638
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• 2009

저온 진공 공정으로 건조된 참치를 유기용매로 추출하여 이들 참치 추출물 및 분획물들에 의한 인체 결장암 및 섬유육종세포에 대한 증식 및 세포 내 활성산소종 억제 효과에 대해 검토하였다. 건조 참치의 A+M 추출물과 MeOH 추출물을 0.5, 1, 및 5 mg/ml의 농도로 인체 섬유육종세포(HT1080)에 처리했을 때 농도 의존적으로 인체 암세포 증식을 억제시켰으며(p<0.05), 특히 A+M 추출물이 MeOH 추출물에 비하여 그 억제효과가 우수하였다. 건조 참치 추출물로부터 얻어진 분획물들의 경우 특히 hexane과 85% aq. MeOH 분획물들에 의한 암세포 증식 억제효과가 높았다. 인체 결장암세포(HT-29)에 대한 결과로 A+M 추출물은 인체 섬유육종세포(HT1080)의 결과와 비교했을 때 다소 암세포 증식 억제 효과가 낮았으나 5 mg/ml의 첨가농도에서 95%로 암세포 증식 억제효과를 보였고(p<0.05), MeOH 추출물도 앞서 A+M 추출물 결과와 유사하게 인체 섬유육종세포(HT1080)에 비해 낮은 암세포 성장 억제효과를 보였지만, 첨가농도 5 mg/ml에서는 93%로 높은 암세포 증식 억제효과를 나타내었다(p<0.05). 건조 참치 분획물들의 경우도 앞서의 인체 섬유육종세포(HT1080)와 유사하게 모든 분획물들에서 농도 의존적으로 억제효과가 높은 것을 살펴 볼 수가 있었고, 인체 결장암세포(HT-29)에서도 hexane과 85% aq. MeOH 분획물에 의한 항암효과가 우수하였다. In vitro 항산화실험에서 건조 참치 A+M 추출물 및 MeOH 추출물을 농도별로 인체 섬유육종세포(HT1080)에 처리하였을 때 A+M 추출물(10 mg/ml 농도)를 제외하고 측정기간 120분 동안 모든 추출물들이 blank군과 control군에 비해 세포 내 활성산소종을 크게 감소시켰다. 건조 참치 분획물들 중 BuOH 및 85% aq. MeOH 분획물들은 세포내 활성산소종을 크게 감소시키는 우수한 항산화 효과를 나타내었다.

• 동의생리병리학회지
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• 제16권2호
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• pp.389-396
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• 2002

In the present work, we examined the mechanism of vasorelaxant effect of scopoletin, an active constituent of Artemisia capillaris on rat thoracic descending aortic rings. Scopoletin induced a concentration-dependent relaxation in rat thoracic descending aortic rings pre-contracted with phenylephrine (EC/sub 50/ = 238.94±37.4 μM), while it was less effective in rat thoracic descending aortic rings precontracted with high potassium solution (KCI 30 mM). Vasorelaxation by scopoletin was significantly inhibited after endothelial removal, but recovered at high concentration. Pretreatment of rat thoracic descending aortic rings with N/sup G/-nitro-L-arginine (100 μM), a nitric oxide synthase inhibitor, and atropine (1 μM), a muscarinic receptor antagonist, significantly inhibited scopoletin-induced relaxation of rat thoracic descending aortic rings. Neither indomethacin (3 μM), an inhibitor of cydooxygenase, nor propranolol (1 μM), a β -adrenoceptor antagonist, modified the effect of scopoletin. The combination of N/sup G/ -nitro-L-arginine (100 μ M) and miconazole (10 μ M), an inhibitor of cytochrome P 450, did not modify the effect of scopoletin, when compared with pretreatment with N/sup G/-nitro-L-arginine(100 μM) alone. Vasorelaxant effect of scopoletin was inverted by pretreatment with diltiazem (10 μM), a Ca/sup 2+/-channel blocker, at low concentration, while restored at high concentration. Apamin (K/sub ca/-channel blocker, 1 μM), 4-aminopyridine (4-AP, K/sub v/-channel blocker, 1 mM), and tetrodotoxin (TTX, Na/sup +/-channel blocker 1 μM) potentiated the vasorelaxant effect of scopoledn, but glibendamide (K/sub ATP/-channel blocker, 10 μM), tetraetylammonium(TEA, non-selective K-channel blocker, 10 mM) did not affect the relaxation of scopoletin. Free radical scavengers (TEMPO, catalase, mannitol) did not modify vascular tone. These results suggest that nitric oxide, Ca/sup 2+/ -channels play a role in endothelium-dependent relaxations to scopoletin in rat aortas, that apamin, 4-AP, TTX but not glibenclamide, TEA potentiated relaxation to scopoletin mediated by these channels, and that free radicals do not concern to the vasorelaxant effect of scopoletin.

• Nutrition Research and Practice
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• 제4권2호
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• pp.93-98
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• 2010

Our previous study demonstrated that methanolic extract of Chrysanthemum zawadskii Herbich var. latilobum Kitamura (Compositae) has the potential to induce detoxifying enzymes such as NAD(P)H:(quinone acceptor) oxidoreductase 1 (EC 1.6.99.2) (NQO1, QR) and glutathione S-transferase (GST). In this study we further fractionated methanolic extract of Chrysanthemum zawadskii and investigated the detoxifying enzyme-inducing potential of each fraction. The fraction (CZ-6) shown the highest QR-inducing activity was found to contain (+)-(3S,4S,5R,8S)-(E)-8-acetoxy-4-hydroxy-3-isovaleroyloxy-2-(hexa-2,4-diynyliden)-1,6-dioxaspiro [4,5] decane and increased QR enzyme activity in a dose-dependent manner. Furthermore, CZ-6 fraction caused a dose-dependent enhancement of luciferase activity in HepG2-C8 cells generated by stably transfecting antioxidant response element-luciferase gene construct, suggesting that it induces antioxidant/detoxifying enzymes through antioxidant response element (ARE)-mediated transcriptional activation of the relevant genes. Although CZ-6 fraction failed to induce hepatic QR in mice over the control, it restored QR activity suppressed by $CCl_4$ treatment to the control level. Hepatic injury induced by $CCl_4$ was also slightly protected by pretreatment with CZ-6. In conclusion, although CZ-6 fractionated from methanolic extract of Chrysanthemum zawadskii did not cause a significant QR induction in mice organs such as liver, kidney, and stomach, it showed protective effect from liver damage caused by $CCl_4$.

• BMB Reports
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• 제53권9호
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• pp.478-483
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• 2020

Kudoa septempunctata is a myxozoan parasite that causes food poisoning in individuals consuming olive flounder. The present study aimed to investigate the currently insufficiently elucidated early molecular mechanisms of inflammatory responses in the intestine owing to parasite ingestion. After Kudoa spores were isolated from olive flounder, HT29 cells were exposed to spores identified to be alive using SYTO-9 and propidium iodide staining or to antigens of Kudoa spores (KsAg). IL-1β, IL-8, TNF-α and NFKB1 expression and NF-κB activation were assessed using real-time PCR, cytokine array and western blotting. The immunofluorescence of FITC-conjugated lectins, results of ligand binding assays using Mincle-Fc and IgG-Fc, CLEC4E expressions in response to KsAg stimulation, and Mincle-dependent NF-κB activation were assessed to clarify the early immune-triggering mechanism. Inflammatory cytokines (IL-1β, GM-CSF and TNF-α), chemokines (IL-8, CCL2, CCL5 and CXCL1) and NF-κB activation (pNF-κB/NF-κB) in HT29 cells increased following stimulation by KsAg. The immunofluorescence results of spores and lectins (concanavalin A and wheat germ agglutinin) suggested the importance of Mincle in molecular recognition between Kudoa spores and intestinal cells. Practically, data for Mincle-Fc and KsAg binding affinity, CLEC4E mRNA expression, Mincle immunofluorescence staining and hMincle-dependent NF-κB activation demonstrated the involvement of Mincle in the early immune-triggering mechanism. The present study newly elucidated that the molecular recognition and immune-triggering mechanism of K. septempunctata are associated with Mincle on human intestinal epithelial cells.

• Journal of Forest and Environmental Science
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• 제30권2호
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• pp.189-200
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• 2014

The tropical wet evergreen, tropical semi evergreen and moist deciduous forest types are projected to be impacted by climate change. In the Western Ghats region, a biodiversity hotspot, evergreen forests including semi evergreen account for 30% of the forest area and according to climate change impact model projections, nearly a third of these forest types are likely to undergo vegetation type change. Similarly, tropical moist deciduous forests which account for about 28% of the forest area are likely to experience change in about 20% of the area. Thus climate change could adversely impact forest biodiversity and product flow to the forest dependent households and communities in Uttara Kannada district of the Western Ghats. This study analyses the distribution of non-timber forest product yielding tree species through a network of twelve 1-ha permanent plots established in the district. Further, the extent of dependence of communities on forests is ascertained through questionnaire surveys. On an average 21% and 28% of the tree species in evergreen and deciduous forest types, respectively are, non-timber forest product yielding tree species, indicating potential high levels of supply of products to communities. Community dependence on non-timber forest products is significant, and it contributes to Rs. 1199 and Rs. 3561/household in the evergreen and deciduous zones, respectively. Given that the bulk of the forest grids in Uttara Kannada district are projected to undergo change, bulk of the species which provide multiple forest products are projected to experience die back and even mortality. Incorporation of climate change projections and impacts in forest planning and management is necessary to enable forest ecosystems to enhance resilience.

• The Korean Journal of Physiology and Pharmacology
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• 제17권3호
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• pp.203-208
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• 2013

As the abnormal proliferation of vascular smooth muscle cells (VSMCs) plays a critical role in the development of atherosclerosis and vascular restenosis, a candidate drug with antiproliferative properties is needed. We investigated the antiproliferative action and underlying mechanism of a newly synthesized naphthoquinone derivative, 5,8-dimethoxy-2-nonylamino-naphthalene-1,4-dione (2-nonylamino-DMNQ), using VSMCs treated with platelet-derived growth factor (PDGF). 2-Nonylamino-DMNQ inhibited proliferation and cell number of VSMCs induced by PDGF, but not epidermal growth factor (EGF), in a concentration-dependent manner without any cytotoxicity. This derivative suppressed PDGF-induced $[^3H]$-thymidine incorporation, cell cycle progression from $G_0/G_1$ to S phase, and the phosphorylation of phosphor-retinoblastoma protein (pRb) as well as the expression of cyclin E/D, cyclin-dependent kinase (CDK) 2/4, and proliferating cell nuclear antigen (PCNA). Importantly, 2-nonylamino-DMNQ inhibited the phosphorylation of PDGF receptor${\beta}$(PDGF-$R{\beta}$) enhanced by PDGF at $Tyr^{579}$, $Tyr^{716}$, $Tyr^{751}$, and $Tyr^{1021}$ residues. Subsequently, 2-nonylamino-DMNQ inhibited PDGF-induced phosphorylation of STAT3, ERK1/2, Akt, and $PLC{\gamma}1$. Therefore, our results indicate that 2-nonylamino-DMNQ inhibits PDGF-induced VSMC proliferation by blocking PDGF-$R{\beta}$ autophosphorylation, and subsequently PDGF-$R{\beta}$-mediated downstream signaling pathways.

• 한국가금학회지
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• 제34권2호
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• pp.91-97
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• 2007

산란계에서 일령에 따른 생리적인 변화를 구명하기 위하여 혈액의 성상이 분석되었다. 13개의 산란계 농장에서 수집된 48계군에서 1, 11, 21, 50, 80, 120, 180, 240, 300, 400, 500일령에 채혈하였으며, 포도당, 지질, 단백질, 효소, 전해질 등 17종의 혈액을 구성하는 물질이 혈액 자동분석기에 의하여 분석되었다. 혈청 내 포도당의 함량은 사료 내 탄수화물의 함량이나 에너지가와 상관없이 부화시에 가장 높고 서서히 감소되는 경향을 보였지만, 총 단백질, 알부민, 그리고 글로불린의 함량은 사료 내 단백질 함량이 감소되었을지라도 일령이 경과함에 따라 증가하였다. 혈청 내 지방 함량은 사료에 포함된 지방의 함량에 관계없이 지방의 종류에 따라 변화가 상이하였다. 콜레스테롤은 부화 시 가장 높고 120일령까지는 낮은 상태를 유지하다가 180일령 이후에 증가하였으나, HDL-콜레스테롤은 부화 시 가장 높고 이후에 서서히 감소하다가 180 일령 이후에는 급격히 감소하였다. 트리글리세라이드는 부화시에 가장 낮고 120일령까지는 부화시보다 약간 높은 수준을 유지하다가 180일령 이후에 10배 이상 급격히 증가하는 경향을 보였다. 효소의 수치는 AST, ALT, 그리고 GGT는 비교적 일정하게 유지되었으나, 아밀라제는 부화 후 일령이 경과함에 따라 서서히 감소되었다. 또한 인, 나트륨, 칼륨, 그리고 염소의 함량은 대체로 일정하게 유지되었으나, 칼슘의 함량은 180일령을 전후로 2배 이상 상승하여 유지되었다. 혈청내 노폐물인 요소와 요산은 부화시 가장 높고 급격히 감소한 후에 요소는 일정하게 유지되었으나, 요산은 120일령부터 증가하여 180일령 이후에는 일정한 상태를 유지하였다. 이 실험의 결과로 혈청 내 칼슘 함량의 변화와 사료 내 칼슘 함량의 변화 간의 상관 관계에 대한 구명이 추후에 필요하지만 혈청 내 존재하는 여러 종류의 혈청 성분은 대부분이 사료의 성상과 관계없이 일령이 경과함에 따라서 대사 변화에 의해 함량이 변화되는 경향을 보였다.