• Title/Summary/Keyword: Tumor metabolism

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High-plasticity mineral trioxide aggregate and its effects on M1 and M2 macrophage viability and adherence, phagocyte activity, production of reactive oxygen species, and cytokines

  • Betania Canal Vasconcellos;Layara Cristine Tomaz Tavares;Danilo Couto da Silva;Francielen Oliveira Fonseca ;Francine Benetti ;Antonio Paulino Ribeiro Sobrinho ;Warley Luciano Fonseca Tavares
    • Restorative Dentistry and Endodontics
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    • v.48 no.1
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    • pp.6.1-6.14
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    • 2023
  • Objectives: This study evaluated the effects of high-plasticity mineral trioxide aggregate (MTA-HP) on the activity of M1 and M2 macrophages, compared to white MTA (Angelus). Materials and Methods: Peritoneal inflammatory M1 (from C57BL/6 mice) and M2 (from BALB/c mice) macrophages were cultured in the presence of the tested materials. Cell viability (MTT and trypan blue assays), adhesion, phagocytosis, reactive oxygen species (ROS) production, and tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β production were evaluated. Parametric analysis of variance and the non-parametric Kruskal-Wallis test were used. Results were considered significant when p < 0.05. Results: The MTT assay revealed a significant decrease in M1 metabolism with MTA-HP at 24 hours, and with MTA and MTA-HP later. The trypan blue assay showed significantly fewer live M1 at 48 hours and live M2 at 48 and 72 hours with MTA-HP, compared to MTA. M1 and M2 adherence and phagocytosis showed no significant differences compared to control for both materials. Zymosan A stimulated ROS production by macrophages. In the absence of interferon-γ, TNF-α production by M1 did not significantly differ between groups. For M2, both materials showed higher TNF-α production in the presence of the stimulus, but without significant between-group differences. Likewise, TGF-β production by M1 and M2 macrophages was not significantly different between the groups. Conclusions: M1 and M2 macrophages presented different viability in response to MTA and MTA-HP at different time points. Introducing a plasticizer into the MTA vehicle did not interfere with the activity of M1 and M2 macrophages.

Anti-inflammatory effect of Althaea rosea L. Callus extract by applying biorenovation (생물전환 기법을 적용한 접시꽃 callus 추출물의 항염증 활성)

  • Yeon-Su Koo;Tae-Jin Park;Jung-Hwan Kim;Seung-Young Kim
    • Journal of Applied Biological Chemistry
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    • v.66
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    • pp.39-45
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    • 2023
  • Biorenovation is a biotransformation method that converts the structure of chemical compounds and natural product through biocatalytic metabolism of microorganism and could enhance biological effectiveness and mitigate cytotoxicity compared to its substrates. Althaea rosea L. has been used as oriental medicine and is known for physiological efficacies such as antiurolithiatic, anti-inflammatory, and anti-cancer activities. A. rosea L. callus, the plant tissue grown to protect its wound, has been reported to have antioxidant and whitening effects. However, mechanisms of its other activity such as inflammation have not yet been investigated. In this study, we extracted A. rosea L. callus (AR) and produced biorenovated AR (ARBR), and then analyzed anti-inflammatory effect in Lipopolysaccharide-induced RAW 264.7 macrophage at 50, 100, 200 ㎍/mL of ARBR. As a result of inhibition test of nitric oxide production, it was found that ARBR was superior to AR without apparent toxicity. Furthermore, ARBR significantly inhibited production of prostaglandin E2, inducible nitric oxide synthase, cyclooxygenase-2 and pro-inflammatory cytokines including Tumor necrosis factor-α, Interleukin-6, Interleukin-1β in a concentration-dependent manner. In conclusion, we suggest that ARBR could regulate the excessive inflammatory response to an appropriate level and be a promising material for functional cosmetics and pharmaceuticals.

Anti-inflammatory Effect of Lactuca sativa L. Extract in Human Umbilical Vein Endothelial Cells and Improvement of Lipid Levels in Mice Fed a High-fat Diet (상추 추출물(Lactuca sativa L.)의 혈관내피세포에서 항염증 작용과 고지방 식이 생쥐에서 혈중 지질농도 개선에 미치는 영향)

  • Hwang-Bo, Jeon;Jang, Kyung Ok;Chung, Hayoung;Park, Jong-Hwa;Lee, Tae Hoon;Kim, Jiyoung;Chung, In Sik
    • The Korean Journal of Food And Nutrition
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    • v.29 no.6
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    • pp.998-1007
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    • 2016
  • The objective of this study was to investigate the effects of a lettuce (Lactuca sativa L.) extract on the inflammation of human umbilical vein endothelial cell (HUVEC) and blood lipid improvement in hypercholesterolemic mice fed a high cholesterol diet. The lettuce extract (100% ethanol extract) inhibited the expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in HUVEC treated with tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$). The lettuce extract suppressed the adhesion of THP-1 to TNF-${\alpha}$-treated HUVEC. The lettuce extract decreased the TNF-${\alpha}$-stimulated production of proinflammatory cytokine interleukin-6, interleukin-8 and chemokine monocyte chemotactic protein 1. In hypercholesterolemic mice, the lettuce extract reduced serum total cholesterol, triglyceride, and low-density lipoprotein-cholesterol level, while the lettuce extract elevated high-density lipoprotein-cholesterol level, resulting in the decrease of atherogenic index and cardiac risk factor level. These results suggested that lettuce extract can be an useful resource to show an anti-inflammatory effect and improve lipid metabolism.

Objectives and Contents of Basic Medical Sciences in Nursing Education (간호학 교육에서 기초의과학 교과목별 목표와 내용에 대한 연구)

  • 최명애;신기수
    • Journal of Korean Academy of Nursing
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    • v.29 no.6
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    • pp.1455-1468
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    • 1999
  • The purpose of this study was to investigate the objectives and contents of basic medical sciences at department of nursing in college of nursing, and junior college of nursing, thus ultimately providing the basic data to standardize the curriculum of the basic medical sciences in nursing education. Seventy eight professors who were in charge of teaching basic medical sciences to at 22 colleges of nursing/ department of nursing, and 20 junior colleges of nursing responded to the questionnaires that consisted of the questions regarding objectives and contents, of basic medical sciences. Based on the description of objectives, the description related to nursing, nurse, nursing science was cathegorized as on objective applicable to nursing science, the description related to medicine or clinical medicine as medical model, the description without description related to medicine was cathegorized as knowledge acquisition. The number of schools corresponding to each category were summerized in descending order. The objectives of basic medical sciences were categorized by concepts and number of schools corresponding to the categorized concept. The findings of the study are as follows ; 1. The subjects of basic medical science identified were physiology, anatomy, biochemistry, pathology, microbiology, and pharmacology in most colleges of nursing and junior colleges. Two colleges of nursing/department of nursing (9.1%) and 19 junior colleges of nursing(95%) did not offer biochemistry, 1 college of nursing /department of nursing(5%) did not offer pathology & pharmacology. 2 junior colleges of nursing (10%) did not offer pharmacology, 1 junior college of nursing(5%) did not offer pathology. The other 1 junior college of nursing did not offer microbiology. 2. Objectives of physiology were to acquire knowledge and understanding on human function in both 6 (50%) colleges and 5 junior colleges. Objectives of anatomy were to acquire knowledge on human structure in both 4 (57%) colleges and 2 (50%) junior colleges; knowledge applicable to nursing sciences in both 3 (42.8%) colleges and 2 (50%) junior colleges. Objectives of biochemistry was to obtain knowledge and understanding on biochemistry, and understanding of basic concepts about biochemistry. Objectives of pathology were to obtain knowledge and understanding on pathology in both 4 (57.1%) colleges and 5(62.5%) junior colleges. Objectives of microbiology were to acquire knowledge and understanding on microbiology in both 5(83.8%) colleges and 6(85.7%) junior colleges. Objectives of pharmacology were to acquire knowledge on pharmacology in both 7(100%) colleges and 8(100%) junior colleges. 3. Contents of physiology in 19 (100%) schools were membrane transport, digestion, circulation, nervous system and respiration. In 16(84.2%) were kidney and muscle, that in 13(68.4%) were endocrine physiology. In 11(57.9%) were introduction and that in 9(47.4%) were structure and function of cells. Contents of anatomy in 11(100%) schools were skeletal system, muscle system, digestive system, circulatory system, concepts regarding human structure. In 10(90.9%) schools were endocrine system and nervous system, and in 5(45.5%) schools were blood, urinary system and cell. Contents of biochemistry in 6(100%) schools were history of biochemistry, body regulating factor, bioenergy, health and nutrition, nutrition of cell, energy production system. In 5(83.3%) schools were metabolism of protein and carbohydrate and enzyme, and in 3(50%) schools were metabolism of energy and fat. Contents of microbiology in 13(100%) schools were environment and influenc of bacteria, virus, G(-) rods, purulent cocci, G(+) rods. In 10 (76.9%) were immunity, diphtheria, enterobacteria, and in 9(69.2%) were spirochete, rickettsia and clamydia, and that in 6(46.2%) were sterilization and disinfection. Contents of pathology in 14(100%) schools were cell injury and adaptation, inflammation, respiratory diseases, circulatory diseases. In 10(71.4%) were neurological disorders, in 8(57.1%) were immunity and disease, and in 7 (50%) were tumor and progressive changes. Contents of pharmacology in 15(100%) were cardivascular drugs, introduction to pharmacology, hypnotics, analgesics, local anesthetics, an ticonvulsants. In 12(80%) were drugs activity on sympathetic and parasympathetic nervous system, and in 11(73%) were sulfa drugs, antibiotics, drug abuse and addiction.

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Inhibitory effect of water-soluble mulberry leaf extract on hepatic lipid accumulation in high-fat diet-fed rats via modulation of hepatic microRNA-221/222 expression and inflammation (고지방식이 급여 쥐에서 수용성 뽕나무 잎 추출물의 간 microRNA-221/222 발현 및 염증 조절을 통한 간 지질 축적억제 효과)

  • Lee, Mak-Soon;Kim, Cheamin;Ko, Hyunmi;Kim, Yangha
    • Journal of Nutrition and Health
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    • v.55 no.2
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    • pp.227-239
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    • 2022
  • Purpose: This study investigated the effects of water-soluble mulberry leaf extract (ME) on hepatic lipid accumulation in high-fat diet-fed rats via the regulation of hepatic microRNA (miR)-221/222 and inflammation. Methods: Male Sprague-Dawley rats (4 weeks old) were randomly divided into 3 groups (n = 7 each) and fed with 10 kcal% low-fat diet (LF), 45 kcal% high-fat diet (HF), or HF + 0.8% ME for 14 weeks. Lipid profiles and cytokine levels of the liver and serum were measured using commercial enzymatic colorimetric and enzyme-linked immunosorbent assay, respectively. The messenger RNA (mRNA) and miR levels in liver tissue were assayed by real-time quantitative reverse-transcription polymerase chain reaction. Results: Supplementation of ME reduces body weight and improves the liver and serum lipid profiles as compared to the HF group. The mRNA levels of hepatic peroxisome proliferator-activated receptor-gamma, sterol regulatory element binding protein-1c, fatty acid synthase, and fatty acid translocase, which are genes involved in lipid metabolism, were significantly downregulated in the ME group compared to the HF group. In contrast, the mRNA level of hepatic carnitine palmitoyl transferase-1 (involved in fatty acid oxidation) was upregulated by ME supplementation. Furthermore, administration of ME significantly downregulated the mRNA levels of inflammatory mediators such as hepatic tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), monocyte chemoattractant protein-1, and inducible nitric oxide synthase. The serum levels of TNF-α, IL-6, and nitric oxide were also significantly reduced in ME group compared to the HF group. Expression of hepatic miR-221 and miR-222, which increase in the inflammatory state of the liver, were also significantly inhibited in the ME group compared to the HF group. Conclusion: These results indicate that ME has the potential to improve hepatic lipid accumulation in high-fat diet-fed rats via modulation of inflammatory mediators and hepatic miR-221/222 expressions.

The Analysis of Blood Glucose Level Difference According to the Exact Use of Blood Glucose Measurement Test Strips in $^{18}F$-FDG Wholebody PET ($^{18}F$-FDG를 이용한 전신 PET 검사에서 혈당 측정 검사지의 정확한 사용에 따른 혈당 수치의 차이 분석)

  • Park, Soon-Ki;Lee, Nam-Ki;NamGung, Chang-Kyung;Jung, Woo-Young
    • The Korean Journal of Nuclear Medicine Technology
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    • v.14 no.2
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    • pp.100-103
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    • 2010
  • Purpose: $^{18}F$-FDG wholebody PET is to evaluate the tumor using glucose metabolism. The blood glucose level is important factor that affects on a result of examination. High glucose levels may interfere with tumor targeting due to competitive inhibition of FDG uptake by D-glucose. The blood glucose level measurement test strips used in the blood glucose measurement are classified into the capillary blood measurement test strips and general purpose measurement test strips that can measure the venous blood and capillary blood altogether depends on cases. The purpose of the study was to compare the blood glucose measurements between simultaneously obtained capillary and venous blood samples using the capillary blood measurement test strips, general purpose measurement test strips. Materials and Methods: A total of 46 subjects (32 males, 14 females) with a mean age of $57.3{\pm}12.3$ years were enrolled. The blood glucose estimation was performed with a Optium Xceed Glucometer (Abbott). Simultaneous capillary and venous blood samples were obtained from each subject. The blood glucose levels were measured using the capillary blood measurement test strips and general purpose measurement test strips. The capillary and venous measurements were compared using a pared t-test. Results: The mean capillary and venous glucose values using the general purpose measurement test strips were $95.2{\pm}12.4$ mg/dL and $104.1{\pm}14.4$ mg/dL, giving a statistically significant difference (p<0.001) between the mean values for the capillary and venous glucose samples (9.0 mg/dL; 95% confidence interval (CI) -11.2 to -6.7). The mean capillary and venous glucose values using the capillary blood measurement test strips were $91.5{\pm}13.6$ mg/dL and $108.6{\pm}16.2$ mg/dL, giving a statistically significant difference (p<0.001) between the mean values for the capillary and venous glucose samples (16.6 mg/dL; 95% CI -20.2 to -13.0). Conclusion: When measuring the blood glucose level before $^{18}F$-FDG PET examination, since the incorrect blood glucose level can be measured, it should note to measure the blood glucose level of the venous blood by the capillary blood measurement test strips. Therefore the measurement variation can be reduced to fulfill the standardized measurement procedure with the suitable measurement test strips, the preparation of the PET examination will be able to be clearly confirmed. In addition, the standardized procedure of the following measurement on the area which is same at all times the blood area in the blood glucose measurement among a capillary or a vein will be needed.

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Analysis of Global Gene Expression Profile of Human Adipose Tissue Derived Mesenchymal Stem Cell Cultured with Cancer Cells (암세포주와 공동 배양된 인간 지방 조직 유래 중간엽 줄기 세포의 유전자 발현 분석)

  • Kim, Jong-Myung;Yu, Ji-Min;Bae, Yong-Chan;Jung, Jin-Sup
    • Journal of Life Science
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    • v.21 no.5
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    • pp.631-646
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    • 2011
  • Mesenchymal stem cells (MSC) are multipotent and can be isolated from diverse human tissues including bone marrow, fat, placenta, dental pulp, synovium, tonsil, and the thymus. They function as regulators of tissue homeostasis. Because of their various advantages such as plasticity, easy isolation and manipulation, chemotaxis to cancer, and immune regulatory function, MSCs have been considered to be a potent cell source for regenerative medicine, cancer treatment and other cell based therapy such as GVHD. However, relating to its supportive feature for surrounding cell and tissue, it has been frequently reported that MSCs accelerate tumor growth by modulating cancer microenvironment through promoting angiogenesis, secreting growth factors, and suppressing anti-tumorigenic immune reaction. Thus, clinical application of MSCs has been limited. To understand the underlying mechanism which modulates MSCs to function as tumor supportive cells, we co-cultured human adipose tissue derived mesenchymal stem cells (ASC) with cancer cell lines H460 and U87MG. Then, expression data of ASCs co-cultured with cancer cells and cultured alone were obtained via microarray. Comparative expression analysis was carried out using DAVID (Database for Annotation, Visualization and Integrated Discovery) and PANTHER (Protein ANalysis THrough Evolutionary Relationships) in divers aspects including biological process, molecular function, cellular component, protein class, disease, tissue expression, and signal pathway. We found that cancer cells alter the expression profile of MSCs to cancer associated fibroblast like cells by modulating its energy metabolism, stemness, cell structure components, and paracrine effect in a variety of levels. These findings will improve the clinical efficacy and safety of MSCs based cell therapy.

A study on the regulatory effect of p-38 MAP kinase on nitric oxide and interleukin-6 in osteoblasts (조골세포에시 p-38 MAP kinase의 nitric oxide 및 interleukin-6 생성조절에 관한 연구)

  • Lee, Kyung-Won;Lee, Doe-Hoon;Kang, Kyung-Hwa;Kim, Sang-Cheol
    • The korean journal of orthodontics
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    • v.33 no.3 s.98
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    • pp.199-210
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    • 2003
  • Tooth movement is the result of bone metabolism in the periodontium, where various cytokines take important roles. Interleukin-6(II-6) and nitrous oxide (NO) were reported to be secreted from osteoblasts in the process of bone resorption. The mechanism of the process has not been clearly understood, but the activation of mitogen-activated protein kinase (MAPK) was known to be an important process in the release of the inflammatory cytotines in macrophages. In this regard, to prove the role of MAPK in the release of IL-6 and NO in MC3T3E-1 osteoblasts, Northern blot analysis, Western blot analysis and immune complex kinase assay were used. As a result, the treatment of MC3T3E-1 osteoblast cultures with combined $interferon-\gamma(IFN-\gamma)$, lipopolysaccharide (LPS) and tumor necrosis $factor-\alpha(TNF-\alpha)$ induces expressions of inducible nitric oxide synthase (iNOS) and IL-6, resulting in sustained releases of large amounts of NO and IL-6. However, $IFN-\gamma,\;LPS,\;and\;TNF-\alpha$ individually induce a non-detectable or small amount of NO and IL-6 in MC3T3E-1 osteoblasts. The role of MAPK activation in the early intracellular signal transduction involved in iNOS and IL-6 transcription in the combined agents-stimulated osteoblasts has been investigated. The p38 MAPK pathway is specifically involved in the combined agents-induced NO and IL-6 release, since NO and IL-6 release in the presence of a specific inhibitor of p38 MAPK, 4-(4-fluorophenyl)-2-(4-metylsulfinylphenyl)-5-(4-metylsulfinylphenyl)-5-(4-pyridyl)imidazole) (SB203580), were significantly diminished. In contrast, PD98059, a specific inhibitor of MEK1, had no effect on NO and IL-6 release. Northern blot analysis showed that the p3a MAPK pathway controlled the iNOS and IL-6 transcription level. These data suggest that p38 MAPK play an important role in the secretion of NO and IL-6 in $LPS/IFN{\gamma}-or\;TNF-\gamma-treated\;MC3T3E-1$ osteoblasts.

The Effect of Gingko Biloba Extract on Energy Metabolic Status in C3H Mouse Fibrosarcoma : Evaluated by in vivo $^{31}P$ Magnetic Resonance Spectroscopy (Gingko biloba extract가 C3H 마우스 섬유육종의 에너지 대사 상태에 미치는 영향 : 생체내 $^{31}P$ 자기공명 분광법을 이용한 분석)

  • Ha Sung Whan;Kim Won Dong;Ahn Yong Chan;Park Chan Il;Lim Tae Hwan;Lee Tae Kuen
    • Radiation Oncology Journal
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    • v.20 no.2
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    • pp.147-154
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    • 2002
  • Purpose : Gingko biloba extract (GBE), a natural product extracted from Gingko leaves, is known to increase the radiosensitivity of tumors. This radiosensitization probably arises from the increase in the peripheral blood flow by decreasing the blood viscosity and relaxing the vasospasm. The influence of a GBE on the metabolic status in fibrosarcoma II (FSall) of a C3H mouse was investigated using $^{31}P$ magnetic resonance spectroscopy (MRS). Materials and Methods : Eighteen C3H mice with fibrosarcoma II $(from\;100\;mm^3\;to\;130\;mm^3)$ were prepared for this experiment. The mice were divided into 2 groups; one (9 mice) without a priming dose, and the other (9 mice) with a priming dose of GBE. The GBE priming dose (100 mg/kg) was administered by an intraperitoneal (i.p.) injection 24 hours prior to the measurement. First $^{31}P$ MRS spectra were measured in the mice from each group as a baseline and test dose of GBE (100 mg/kg) was then administered to each group. One hour later, the $^{31}P$ MRS spectra were measured again to evaluate the change in the energy metabolic status. Results : In the group without the priming dose, the mean pH, PCr/Pi, PME/ATP, Pi/ATP, PCr/(Pi+PME) values 1 hour after the test dose were not changed significantly compared to the values at the baseline. However, in the group with the priming dose, the mean PCr/Pi, Pi/ATP, PCr/(Pi+PME) values 1 hour after the test dose changed from the baseline values of 0.49, 0.77, 0.17 to 0.74, 0.57, 0.28 respectively. According to the paired t-test, the differences were statistically significant. Conclusion : The above findings suggest that the metabolic status is significantly improved after administering GBE if the priming dose is given 24 hours earlier. This shows that the radiosensitizing effect of GBE is based on the increase of tumor blood flow and the improvement in the metabolic status.

Immunostimulatory and Anti-Obesity Activity of Lonicera insularis Nakai Extracts in Mouse Macrophages RAW264.7 Cells and Mouse Adipocytes 3T3-L1 Cells (섬괴불나무(Lonicera insularis Nakai) 추출물의 면역자극 및 항비만 활성)

  • Yu, Ju Hyeong;Yeo, Joo Ho;Choi, Min Yeong;Lee, Jae Won;Geum, Na Gyeong;An, Mi-Yun;Jeong, Jin Boo
    • Korean Journal of Plant Resources
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    • v.35 no.4
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    • pp.417-427
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    • 2022
  • In this study, we investigated in vitro immuno-stimulatory and anti-obesity activity of fruit (LIF), leaves (LIL) and stems (LIS) from Lonicera insularis Nakai in mouse macrophages RAW264.7 cells and mouse pre-adipocytes 3T3-L1 cells. LIF, LIL and LIS increased the production of immunostimulatory factors such as nitric oxide (NO), inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α) and activated phagocytosis in RAW264.7 cells. Inhibition of toll-like receptor 2/4 (TLR2/4) partly blocked LIF, LIL and LIS mediated production of immunostimulatory factors. In addition, inhibition of mitogen-activated protein kinases (MAPK) signaling attenuated the production of immunostimulatory factors induced by LIF, LIL and LIS. Based on these results of this study, LIF, LIL and LIS is thought to activate macrophages the production of immunostimulatory factors and phagocytosis through toll-like receptor 2/4 (TLR2/4) and MAPKs signaling pathway. In anti-obesity study, LIF reduced the lipid accumulation in 3T3-L1 cells. LIF increased the protein phosphorylation expressions such as AMP-activated protein kinase (AMPK), hormone sensitive lipase (HSL), adipose triglyceride lipase (ATGL) related to the lipolysis of the adipocytes. In addition, LIF increased the expression of proteins involved in energy metabolism and brown adipose tissues differentiation such as peroxisome proliferator-activated receptor gamma coativator 1α (PGC-1α) and PR domain-containing16 (PRDM16). These results suggest that LIF is involved in lipid accumulation inhibition through expressing the proteins such as lipolysis and differentiation of white adipocytes to brown adipocytes.