• Biomolecules & Therapeutics
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• 제30권6호
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• pp.616-624
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• 2022

Mebendazole (MBZ), a microtubule depolymerizing drug commonly used for the treatment of helminthic infections, has been suggested as a repositioning candidate for the treatment of brain tumors. However, the efficacy of MBZ needs further study to improve the beneficial effect on the survival of those patients. In this study, we explored a novel strategy to improve MBZ efficacy using a drug combination. When glioblastoma cells were treated with MBZ, cell proliferation was dose-dependently inhibited with an IC₅₀ of less than 1 µM. MBZ treatment also inhibited glioblastoma cell migration with an IC₅₀ of less than 3 µM in the Boyden chamber migration assay. MBZ induced G2-M cell cycle arrest in U87 and U373 cells within 24 h. Then, at 72 h of treatment, it mainly caused cell death in U87 cells with an increased sub-G1 fraction, whereas polyploidy was seen in U373 cells. However, MBZ treatment did not affect ERK1/2 activation stimulated by growth factors. The marked induction of autophagy by MBZ was observed, without any increased expression of autophagy-related genes ATG5/7 and Beclin 1. Co-treatment with MBZ and the autophagy inhibitor chloroquine (CQ) markedly enhanced the anti-proliferative effects of MBZ in the cells. Triple combination treatment with temozolomide (TMZ) (another autophagy inducer) further enhanced the anti-proliferative effect of MBZ and CQ. The combination of MBZ and CQ also showed an enhanced effect in TMZ-resistant glioblastoma cells. Therefore, we suggest that the modulation of protective autophagy could be an efficient strategy for enhancing the anti-tumor efficacy of MBZ in glioblastoma cells.

• 대한화장품학회지
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• 제48권3호
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• pp.265-273
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• 2022

본 연구에서는 한국산 겨우살이 (Viscum album L. var. coloratum)이 아토피 피부염과 관련된 염증성 사이토카인에 영향을 미치는지 여부를 알아보았다. 실험에는 헥산, 부탄올, 에틸아세테이트, 메틸렌클로라이드, 총 4 가지 분획물을 사용하였으며, RAW264.7 마우스 대식세포와 RBL-2H3 렛트 호중구를 이용하여 염증성 마커를 연구하였다. 실험 결과 에틸아세테이트 분획이 tumor necrosis factor alpha (TNF-α), interleukin(IL)-6, IL-4의 mRNA 발현 및 단백질 분비량을 감소시켰으나, 헥산 분획은 뚜렷한 효능이 없었다. 또한 부탄올 분획은 IL-4, IL-6의 mRNA 발현을 감소시켰고, 메틸렌클로라이드 분획은 IL-4와 TNF-α의 mRNA 발현을 감소시켰다. 결과적으로 한국산 겨우살이(V. album var. coloratum)가 아토피 피부염과 관련된 사이토카인 분비를 억제시켜 항염증 효과를 나타낼 수 있으므로, 이와 관련된 기능성 화장품 개발이 가능할 것으로 사료된다.

• 한국가축번식학회지
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• 제17권1호
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• pp.13-19
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• 1993

We investigated the effects of CP-2 extracted from the mixture of Copis and Croton tiglium L, which showed very high cytotoxic effect to the various tumor cells, on the growth and steroidenesis of primary and transformed cell lines PA-GS6 and PO-GRS1 by cotransfectionwith SV40 and Ha ras oncogenes. CP-2 inhibited the growth of PA-GS6 and PO-GRS1 in a dose dependent manner when the growth of them was measured by cell number and by protein content, while CP-2 did not affect the growth of primary granulose cells. Productions of progesterone ofprimary and transformed granulosa cells were stimulated by forskolin, but this stimulatory effect was blocked by treatment of CP-2. Clinical application of CP-2 asa new anti-cancer drug and utilization of transformed granulosa cells as a model system for the screening of anti-cancer drug were also discussed.

• 산업식품공학
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• 제15권1호
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• pp.1-5
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• 2011

Codonopsis lanceolata L. (Campanulaceae) has long been used in traditional Korean medicine to treat bronchitis, cough, and inflammatory diseases, however, the efficacy of anti-tumor activities remains to be defined. In this study the effects of Codonopsis lanceolata (C. lanceolata) on proliferation, migration and adhesion in lung (A549, H1299) and ovarian cancer (SKOV-3) cells were investigated. To assess and compare the pharmacological effects and production places of C. lanceolata, the ethanolic extracts of C. lanceolata from different places in Korea (Hongseong, Yecheon, Yeongwol, Yanggu, Gangjin, and Hoengseong) were prepared. The extract from Hoengseong county did have only marginal anti-proliferative activity in all the cell lines tested, however, other extracts had little or no effect on cell proliferation. The extracts from Hongseong, Gangjin or Hoengseong county had partial anti-migratory activity in lung cancer cells, but not in ovarian cancer cells. In addition, the extract from Hoengseong county had partial anti-adhesive activity in ovarian cancer cells, however, other extracts did not affect cell adhesion in both lung and ovarian cancer cells. Taken together, these findings provide the first description of anti-tumor efficacy of C. lanceolata from different production places in Korea, and suggest that C. lanceolata from Hoengseong county may have therapeutic potential in lung and ovarian cancers.

• Nutrition Research and Practice
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• 제10권5호
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• pp.494-500
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• 2016

BACKGROUND/OBJECTIVES: Evidence indicates that berry anthocyanins are anti-atherogenic, antioxidant, and anti-inflammatory. However, berries differ vastly in their anthocyanin composition and thus potentially in their biological and metabolic effects. The present study compared hypolipidemic, antioxidant, and anti-inflammatory properties of blueberry (BB), blackberry (BK), and blackcurrant (BC) in a diet-induced obesity (DIO) mouse model. MATERIALS/METHODS: Male C57BL/6J mice were fed a high fat (HF; 35% fat, w/w) control diet or a HF diet supplemented with freeze-dried 5% BB, 6.3% BK or 5.7% BC for 12 weeks (10 mice/group) to achieve the same total anthocyanin content in each diet. Plasma lipids, antioxidant status and pro-inflammatory cytokines were measured. The expression of genes involved in antioxidant defense, inflammation, and lipid metabolism was determined in the liver, epididymal adipose tissue, proximal intestine, and skeletal muscle. Histological analysis was performed to identify crown-like structure (CLS) in epididymal fat pads to determine macrophage infiltration. RESULTS: No differences were noted between the control and any berry-fed groups in plasma levels of liver enzymes, insulin, glucose, ferric reducing antioxidant power, superoxide dismutase, and tumor necrosis factor ${\alpha}$. However, BK significantly lowered plasma triglyceride compared with the HF control and other berries, whereas BC significantly reduced F4/80 mRNA and the number of CLS in the epididymal fat pad, indicative of less macrophage infiltration. CONCLUSIONS: The present study provides evidence that BB, BK and BC with varying anthocyanin composition differentially affect plasma lipids and adipose macrophage infiltration in DIO mice, but with no differences in their antioxidant capacity and anti-inflammatory potential.

• 대한화장품학회지
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• 제42권3호
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• pp.235-245
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• 2016

본 연구에서는 히알루론산나트륨(sodium hyaluronate, HA)을 효소 분해하여 분자량 크기(1, 10, 50, 100, 660, 및 1500 kDa) 별로 제조한 뒤 콜라겐 합성 및 항염증 활성에 미치는 영향과 피부투과도를 조사하였다. 이들 HA는 인간피부세포인 Hs68 세포에 세포독성을 나타내지 않았다. 콜라겐 생합성능은 1500 kDa, 50, kDa HA가 각각 59, 50%로 콜라겐 생합성 촉진능이 우수한 것으로 나타났다. 분자량 크기에 따른 HA의 피부투과도를 측정한 결과 660 또는 1500 kDa의 HA은 2% 미만의 미미한 투과율을 보였으나, 저분자 HA (1, 10, 또는 50 kDa)은 시간이 지남에 따라 투과율이 증가하는 것을 확인하였다. 마우스 대식세포인 RAW 264.7 세포에서 HA 분자량 크기에 따른 항염증 효과를 확인한 결과, 50 kDa HA가 농도 의존적으로 nitric oxide 및 tumor necrosis factor-${alpha}$ 합성을 저해하여 다른 분자량의 HA (1, 10, 및 100 kDa)에 비해 가장 큰 항염증 효능을 나타냈다. 현재까지 효소(hyaluronidase) 처리하여 제조된 다양한 크기의 분자량(1, 10, 50, 100, 660, 1500 kDa)의 HA 중 50 kDa HA가 collagen의 합성, 항염증 및 피부 흡수도에 대한 종합적인 평가를 한 사례는 없었다. 따라서 이러한 연구결과는 50 kDa의 HA가 인간피부세포에서 콜라겐 합성을 증진시키고, 피부 투과율을 높으며 피부 주름을 유발하는 염증반응을 억제함으로써 피부노화 및 주름 개선용 화장품소재로 개발될 수 있는 가능성을 보여준다.

• Applied Microscopy
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• 제48권3호
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• pp.62-72
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• 2018

This study investigated the anti-obesity effect of a pear (Fructus Pyri Pyrifoliae) extract fermented by lactic-acid bacteria on obesity induced by a high-fat diet in rats. Body-weight measurement, blood analysis, and light microscope observation of adipose tissue in liver and epididymis were conducted after 8 weeks. Gene expression of leptin, adiponectin, and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) in liver cells were also investigated. Compared to CON, PFA and PFB showed 8% weight reduction along with weight reduction of adipose tissue in liver and epididymis. Observing the microstructure of liver cells showed that lipid droplets were smaller in PFA and PFB than in CON. We confirmed that Fructus Pyri Pyrifoliae extract fermented by lactic-acid bacteria can affect gene expression of leptin, adiponectin, and $TNF-{\alpha}$ in liver cells, showing an obesity treatment effect. From the results above, it was observed that weight gain from increased gene expression in adipose cells as well as from the increased proportion of adipose cells caused by a high-fat diet can be statistically significantly reduced by taking Fructus Pyri Pyrifoliae extract fermented by lactic-acid bacteria. Therefore, Fructus Pyri Pyrifoliae extract fermented by lactic-acid bacteria can be effective for preventing and treating obesity by reducing weight and adipose cells.

• 한국식품영양학회지
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• 제32권4호
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• pp.275-283
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• 2019

This study was carried out to investigate the various roles and effects of Morinda citrifolia L.(noni) on the human body and to utilize the findings obtained for future disease related research on food and nutrition. Morinda citrifolia L. has been used in folk medicine by Polynesians for over 2,000 years and is reported to have a broad range of therapeutic effects. Noni is an alkaloid system such as proxeronine, scopoletin, octanoic acid, terpenoids, alkaloids, anthraquinones, nordamnacanthal, morindone, rubiadin, b-sitosterol, flavone glycosides, linoleic acid, acubin, L-asperuloside, caproic acid, caprylic acid, ursolic acid, rutin. Noni's side effects have been reported to affect anti-inflammatory, analgesics, LDL antioxidant, anti-tumor, antifungal, antibiotic, antiviral, antiparasitic and immunosuppressive effects. In particular, noni's efficacy is considered to be important for the prevention of diseases by inhibiting active oxygen, which is a direct cause of oxidative stress, through various metabolites through 'xeronine system'. Noni's functions and effects that have been examined in this study include anti-inflammation, pain relief, antioxidant, anticancer, hepatocyte protection among others. Therefore, noni's extracts are considered highly useful for diverse scientific and nutritional health functional foods.

• 사상체질의학회지
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• 제22권4호
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• pp.56-64
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• 2010

1. Objectives 4 herbal formulas (Yanggyeoksanhwa-tang, Yeoldahanso-tang, Cheongsimyeonja-tang and Taeeumjowi-tang) were applied to investigate the anti-inflammatory activities. In many studies, plant-derived anti-inflammatory efficacies have been investigate for their potential inhibitory effects on lipopolysaccharide (LPS)-stimulated macrophages. This study was performed to examine the anti-inflammatory activities of 4 herbal formulas on LPS-stimulated RAW 264.7 cells. 2. Methods The productions of nitric oxide (NO), prostaglandin (PG)$E_2$, interleukin(IL)-6 and tumor necrosis factor (TNF)-${\alpha}$ were examined in the presence of the 4 herbal formulas in RAW 264.7 cells. The cells were incubated with LPS 1 ${\mu}g/mL$ and 4 herbal formulas for 18 hrs. The anti-inflammatory activity of 4 herbal formulas were investigate by carrageenin-induced paw edema in rats. The paw volume was measured at 2 and 4 hrs following carrageenininduced paw edema in rats. 3. Results Yanggyeoksanhwa-tang and Cheongsimyeonja-tang showed inhibitory effect on $PGE_2$ production in LPS-stimulated RAW 264.7 cells and a reduction in carrageenin-induced paw edema on rats. Yanggyeoksanhwa-tang showed inhibitory effect on IL-6 in LPS-stimulated RAW 264.7 cells. 4 herbal formulas not affect on NO and TNF-${\alpha}$ inhibition in LPS-stimulated RAW 264.7 cells. 4. Conclusions These results suggested that Yanggyeoksanhwa-tang and Cheongsimyeonja-tang have anti-inflammatory activity.

• 대한한방부인과학회지
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• 제34권1호
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• pp.34-47
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• 2021

Objectives: This study was designed to examine anti-inflammatory effect and mechanism of Citri Reticulatae Viride Pericarpium water extract (CRE). Methods: Cell cytotoxicity was tested with RAW 264.7 cells. To investigate anti-inflammatory effect of CRE in lipopolysaccharide (LPS)-induced RAW 264.7 cell, we measured nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10). In addition, mitrogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) were examined by western blotting in LPS-induced RAW 264.7 cell with treated CRE. Results: In cytotoxicity analysis, CRE does not affect cell cytotoxicity. As compared with the control group, the expression of NO, PGE2, TNF-α, IL-6 were significantly decreased, and IL-10 was significantly increased in LPS-induced RAW 264.7 cell with treated CRE. As a result of Western blotting, there was concentration-dependent inhibition of pp38, pERK in MAPK pathway and significant reduction of pp65 in the NF-κB pathway. Conclusions: CRE might have anti-inflammatory effect in LPS-induced macrophages by promoting the production of IL-10.