• Title/Summary/Keyword: tumor inhibition

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Anti-inflammatory activity of a sulfated polysaccharide isolated from an enzymatic digest of brown seaweed Sargassum horneri in RAW 264.7 cells

  • Sanjeewa, Kalu Kapuge Asanka;Fernando, Ilekkuttige Priyan Shanura;Kim, Eun-A;Ahn, Ginnae;Jee, Youngheun;Jeon, You-Jin
    • Nutrition Research and Practice
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    • v.11 no.1
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    • pp.3-10
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    • 2017
  • BACKGROUND/OBJECTIVES: Sargassum horneri is an edible brown alga that grows in the subtidal zone as an annual species along the coasts of South Korea, China, and Japan. Recently, an extreme amount of S. horneri moved into the coasts of Jeju Island from the east coast of China, which made huge economic and environmental loss to the Jeju Island. Thus, utilization of this biomass becomes a big issue with the local authorities. Therefore, the present study was performed to evaluate the anti-inflammatory potential of crude polysaccharides (CPs) extracted from S. horneri China strain in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. MATERIALS/METHODS: CPs were precipitated from S. horneri digests prepared by enzyme assistant extraction using four food-grade enzymes (AMG, Celluclast, Viscozyme, and Alcalase). The production levels of nitric oxide (NO) and pro-inflammatory cytokines, including tumor necrosis factor (TNF)-${\alpha}$ and interleukin (IL)-$1{\beta}$ were measured by Griess assay and enzyme-linked immunosorbent assay, respectively. The levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), nuclear factor (NF)-${\kappa}B$, and mitogen-activated protein kinases (MAPKs) were measured by using western blot. The IR spectrums of the CPs were recorded using a fourier transform infrared spectroscopy (FT-IR) spectrometer. RESULTS: The polysaccharides from the Celluclast enzyme digest (CCP) showed the highest inhibition of NO production in LPS-stimulated RAW 264.7 cells ($IC_{50}$ value: $95.7{\mu}g/mL$). Also, CCP dose-dependently down-regulated the protein expression levels of iNOS and COX-2 as well as the production of inflammatory cytokines, including TNF-${\alpha}$ and IL-$1{\beta}$, compared to the only LPS-treated cells. In addition, CCP inhibited the activation of NF-${\kappa}B$ p50 and p65 and the phosphorylation of MAPKs, including p38 and extracellular signal-regulated kinase, in LPS-stimulated RAW 264.7 cells. Furthermore, FT-IR analysis showed that the FT-IR spectrum of CCP is similar to that of commercial fucoidan. CONCLUSIONS: Our results suggest that CCP has anti-inflammatory activities and is a potential candidate for the formulation of a functional food ingredient or/and drug to treat inflammatory diseases.

Saprolegnia parasitica Isolated from Rainbow Trout in Korea: Characterization, Anti-Saprolegnia Activity and Host Pathogen Interaction in Zebrafish Disease Model

  • Shin, Sangyeop;Kulatunga, D.C.M.;Dananjaya, S.H.S.;Nikapitiya, Chamilani;Lee, Jehee;De Zoysa, Mahanama
    • Mycobiology
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    • v.45 no.4
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    • pp.297-311
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    • 2017
  • Saprolegniasis is one of the most devastating oomycete diseases in freshwater fish which is caused by species in the genus Saprolegnia including Saprolegnia parasitica. In this study, we isolated the strain of S. parasitica from diseased rainbow trout in Korea. Morphological and molecular based identification confirmed that isolated oomycete belongs to the member of S. parasitica, supported by its typical features including cotton-like mycelium, zoospores and phylogenetic analysis with internal transcribed spacer region. Pathogenicity of isolated S. parasitica was developed in embryo, juvenile, and adult zebrafish as a disease model. Host-pathogen interaction in adult zebrafish was investigated at transcriptional level. Upon infection with S. parasitica, pathogen/antigen recognition and signaling (TLR2, TLR4b, TLR5b, NOD1, and major histocompatibility complex class I), pro/anti-inflammatory cytokines (interleukin $[IL]-1{\beta}$, tumor necrosis factor ${\alpha}$, IL-6, IL-8, interferon ${\gamma}$, IL-12, and IL-10), matrix metalloproteinase (MMP9 and MMP13), cell surface molecules ($CD8^+$ and $CD4^+$) and antioxidant enzymes (superoxide dismutase, catalase) related genes were differentially modulated at 3- and 12-hr post infection. As an anti-Saprolegnia agent, plant based lawsone was applied to investigate on the susceptibility of S. parasitica showing the minimum inhibitory concentration and percentage inhibition of radial growth as $200{\mu}g/mL$ and 31.8%, respectively. Moreover, natural lawsone changed the membrane permeability of S. parasitica mycelium and caused irreversible damage and disintegration to the cellular membranes of S. parasitica. Transcriptional responses of the genes of S. parasitica mycelium exposed to lawsone were altered, indicating that lawsone could be a potential anti-S. parasitica agent for controlling S. parasitica infection.

The Composition and Bioactivities of Ganoderan by Mycelial Fractionation of Ganoderma lucidum IY009 (영지 IY009 균사체의 분획에 따라 추출된 ganoderan의 조성과 생리적 활성)

  • Han, Man-Deuk;Jeong, Hoon;Lee, June-Woo;Back, Sung-Jin;Kim, Su-Ung;Yoon, Kyung-Ha
    • The Korean Journal of Mycology
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    • v.23 no.4 s.75
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    • pp.285-297
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    • 1995
  • Ganoderan, an immunomodulating ${\beta}-glucan$ of G. lucidum, induces potent antitumor immunity in tumor-bearing mice. The present study was set up to elucidate the chemical composition and bioactivities of ganoderan obtained from the mycelial fractionation of G. lucidum IY009. Ganoderan was isolated and purified from its extracellular, cell wall and cytoplasmic sources. These ganoderans were composed mainly of glucose. The cell wall-alkali soluble-water soluble fraction (CW-AS-WS) showed the highest antitumor activity (inhibition rate of 94%) in sarcoma-bearing mice and 37% of anticomplementary activity. The CW-AS-WS fraction was found to be approximately average 20,000 dalton in aq. 0.3N NaOH solution and composed of 88% carbohydrate and 4% protein. The carbohydrate of the CW-AS-WS was composed of 74% glucose. These results indicate that the ganoderans extracted from the mycelial fractionations of G. lucidum IY009 had different chemical characteristics and showed different potentiality in antitumor and anticomplementary activity.

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The Inhibitory Effects of Yukmijihwang-tang-Hap-Sabaek-san and Root Cortex of Morus alba L. on the IL-6, IL-8 and GM-CSF mRNA Levels in Human Epithelial Cells (육미지황탕합사백산(六味地黃湯合瀉白散)과 상백피(桑白皮)가 인간 기관지상피세포의 IL-6, IL-8, GM-CSF mRNA level에 미치는 영향)

  • Hwang, Woo-Suck;Heo, Tae-Seok;Jung, Hee-Jae;Jung, Sung-Ki;Rhee, Hyung-Koo;Ju, Chang-Yeop
    • The Journal of Internal Korean Medicine
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    • v.22 no.3
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    • pp.415-422
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    • 2001
  • Objectives: We aimed to identify the dose-dependent inhibitory effects of Yukmijihwang-tang-Hap-Sabaek-san(YMHSB) and Root cortex of Morus alba L.(RCM) on the mRNA expression of Interieukin(IL)-6, IL-S, granulocyte macrophage colony stimulating factor(GM-CSF) involved in the asthma model. Methods: In this study BEAS-2B cell lines, human epithelial cells, were used. These cells were stimulated by tumor necrosis $factor(TNF)-{\alpha},\;IL-1{\beta}$ and histamine for artificial inflammatory expression. ${\beta}-actin$ messenger RNA(mRNA) was used for the internal standard. After each 24 hours of the YMHSB and RCM treatment, total cellular RNAs were collected by treating RNA zol directly on the living cells. Then the transcriptional activities of IL-6, 8 and GM-CSF were measured by RT-PCR with electrophoresis. Results: In the YMHSB study, the mRNA expression of GM-CSF and IL-8 is significantly inhibited compared to that of control group. But the mRNA expression of IL-6 is not significantly inhibited. In the RCM study, the mRNA expression of GM-CSF and IL-S is significantly inhibited compared to that of control group. But the mRNA expression of IL-6 is not significantly inhibited. Conclusions: This study shows that YMHSB and RCM have dose-dependent inhibitory effects on the mRNA expression of IL-S and GMCSF in human epithelial cells. So these herbal medicines may inhibit the inflammatory process of asthma. Advanced studies are required to investigate the mechanisms of inhibition by herbal medicine in the asthma model.

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Effects of GyeongshinhaeGihwan 1(GGT1) on the Expression of Obesity-related Genes in Obese Male hGHTg Rats (경신해지환(輕身解脂丸) (GGT1)이 형질전환 비만모델 hGHTg 수컷 쥐의 비만관련 유전자 발현에 미치는 영향)

  • Jung Yang-Sam;Yoon Mi-Chung;Kim Gyeong-Cheol;Shin Soon-Shik
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.1
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    • pp.93-97
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    • 2006
  • To investigate whether GyeongshinhaeGihwan 1(GGT1), an anti-obesity herbal medicine widely used in oriental medicine, regulates the expression of obesity-related genes, we measured the changes in mRNA levels of these genes by GGT1 in human growth hormone transgenic (hGHTg) obese male rats, and these effects by GGT1 were compared with those of reductil (RD), an anti-obesity drug approved by FDA. Rats received once daily oral administrations of autoclaved water, RD, or GGT1 for 8 weeks. At the end of study, rats were sacrificed and tissues were harvested. Total RNA from adipose tissue, liver and kidney was prepared and the mRNA levels for LPL (lipoprotein lipase), PPAR $\gamma$ (peroxisome proliferator activated receptor-gamma), PPAR$\delta$ (peroxisome proliferator activated receptor-delta), leptin, TNF$\alpha$ (tumor necrosis factor-alpha), and internal standard G3PDH (glyceraldehyde-3- phosphate dehydrogenase) were analyzed by RT-PCR. PPAR$\gamma$ mRNA levels of liver and kidney were decreased in drug-treated groups compared with control group and the decrease of PPAR$\gamma$ expression was more prominent in GGT1 group than in RD group, suggesting that GGT1 is effective in the inhibition of adipogenesis and lipid storage by decreasing the PPAR$\gamma$ expression. In contrast, PPAR$\delta$ mRNA levels of adipose tissue and kidney were increased by RD and GGT1 , and the magnitudes of increase were higher in GGT1 group than in RD group, indicating that GGT1 stimulates fatty acid oxidation and energy metabolism by activating PPAR$\delta$ expression, Compared with control and RD groups, GGT1 group had higher concentrations of serum leptin, a well-known inhibitor of appetite. However, The mRNA levels of leptin, LPL, and TNF$\alpha$ were not changed by GGT1 and RD, compared with DW. These results demonstrate that GGT1 not only decreases PPAR$\gamma$ expression of liver and kidney, but also increases PPAR$\delta$ expression of adipose tissue and kidney, leading to the regulation of obesity and that these effects were more pronounced in GGT1 group compared with RD group. In addition, GGT1 seems to prevent obesity by increasing the serum leptin levels.

Regulatory Effect of Gigukjihwangtanggami on Cytokine Production in Patients with Cerebral Infarction

  • Lee, Min-Goo;Park, Sae-Wook;Lee, Sun-Woo;Son, Ji-Woo;Kang, Baek-Gyu;Park, Sang-Moo;Lee, In;Moon, Byung-Soon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.4
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    • pp.1044-1050
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    • 2006
  • The Korean genuine medicine, 'Gigukjihwangtanggami (GJT)' has long been used clinically for hypertension and various cerebrovascular diseases. However, experimental study has been carried out very little. Recently cytokines involved in the regulation of inflammatory reactions and immune responses may play an important role in the pathogenesis of cerebral infarction (CI). The aim of this study is to investigate the effect of GJT on the production of pro-inflammatory cytokines and anti-inflammatory cytokines in peripheral blood mononuclear cells (PBMCS) stimulated with lipopolysaccaride (LPS) from Cl patients. The amount of tumor necrosis $factor-{\alpha}\;(TNF-{\alpha}),\;interleukin-1{\beta}\;(IL-1{\beta})$, IL-6, IL-8, IL-4 and IL-10 in PBMC culture supernatant was significantly increased in the LPS treated cells compared to unstimulated cells. GJT inhibited the production of $TNF-{\alpha},\;IL-1{\beta}$, IL-6 and IL-8 induced by LPS. The maximal inhibition rate of the $TNF-{\alpha},\;IL-1{\beta}$, IL-6 and IL-8 production by pretreatment of GJT (1 mg/ml) was $57.32{\pm}2.5%$ (p.0.05), $42.02{\pm}3.5%$ (p.0.05), $40.02{\pm}2.3%$ (p.0.05) and $48.02{\pm}3.1$, (p.0.05), respectively. In the Other hand, GJT increased the production of IL-4 and IL-10. The maximal increase rate of the IL-4 and IL-10 production by pretreatment of GJT (1 mg/ml) was $42.4{\pm}3.3%$ (p.0.05) End $56.4{\pm}2.9%$ (p.0.05), respectively. Taken together, these results indicate that GJT Ray have regulatory effects on the cytokine production and suggest that GJT might use clinically for the treatment of CI.

Effect of Glutathione on Lead Induced Modulation of NO Synthesis in RAW 264.7 Cell (RAW 264.7 Cell에서 납에 의한 NO 생성의 조절에 미치는 Glutathione의 효과)

  • Oh, Gyung-Jae;Kwon, Keun-Sang;Yoon, Wook-Hee;Shin, Sae-Ron
    • Journal of Preventive Medicine and Public Health
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    • v.35 no.4
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    • pp.269-274
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    • 2002
  • Objectives : To evaluate the elect of glutathione(GSH) on lead induced modulation of nitric oxide(NO) synthesis, and to examine how lead modulates NO production in macrophages. Methods : This study was observed in a culture of RAW 264.7 cells, which originated from a tumor in a Balb/c mouse that was induced by the Abelson murine leukemia virus. The compounds investigated were lead chloride, N-acetyl-cystein(NAC), and Buthionine Sulfoximine( BSO). Results : ATP synthesis in RAW 264.7 cells was unchanged by each lead concentration exposure in a dose dependent manner. The NO synthesis was decreased when exposed to lead($PbCl_2$) concentration $0.5{\mu}M$. The presence of $300{\mu}M$ NAC, used as a pretreatment in the culture medium, caused the recovery of the lead induced decrease in NO synthesis, but in the presence of $300{\mu}M$ BSO as a pretreatment, there was no recoverey. Pretreatment with NAC and BSO had no affect on ATP synthesis at any of the lead concentrations used. Conclusions : These results indicated that GSH has a protective effect toward lead toxicity, and suggested that the inhibition of NO production in macrophage due to lead toxicity may be related to cofactors of iNOS (inducible nitric oxide synthase)

Delphinidin Suppresses Angiogenesis via the Inhibition of HIF-1α and STAT3 Expressions in PC3M Cells (전립선 암세포에서 delphinidin에 의한 HIF-1α와 STAT3 억제를 통한 혈관내피 성장 인자 발현 저해 효과)

  • Kim, Mun-Hyeon;Kim, Mi-Hyun;Park, Young-Ja;Chang, Young-Chae;Park, Yoon-Yub;Song, Hyun-Ouk
    • Korean Journal of Food Science and Technology
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    • v.48 no.1
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    • pp.66-71
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    • 2016
  • Delphinidin is a blue-red pigment and one of the major anthocyanins in plants. It plays an important role in anti-oxidant, anti-inflammatory, anti-mutagenic and anti-cancer properties. In this study, we investigated the inhibitory effects of delphinidin on vascular endothelial growth factor (VEGF) gene expression, an important factor involved in angiogenesis and tumor progression in human prostate cancer. Delphinidin decreased levels of epidermal growth factor (EGF)-induced VEGF mRNA expression in PC-3M cells. The expression of the EGF-induced hypoxia inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$) and signaling transducer and activator of transcription 3 (STAT3) proteins, which are the major transcription factors for VEGF, were inhibited by delphinidin. In addition, delphinidin decreases HRE-promoter reporter gene activity, suggesting that delphinidin can suppress the transcription of HIF-$1{\alpha}$ under EGF induction, leading to a decrease in the expression of VEGF. Delphinidin specifically suppressed the phosphorylation of Akt, p70S6K, and 4EBP1, but not the phosphorylation of EGFR. Therefore, our results suggest that delphinidin may inhibit human prostate cancer progression and angiogenesis by inhibiting HIF-$1{\alpha}$, STAT3 and VEGF gene expression.

Carotenoids Components of Tunicata, Shellfishes and Its Inhibitory Effects on Mutagenicity and Growth of Tumor Cell (미색동물 및 패류의 Carotenoids 색소성분과 돌연변이 및 종양세포 증식의 억제효과)

  • 하봉석;백승한;김수영
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.29 no.5
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    • pp.922-934
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    • 2000
  • To investigate the composition of carotenoids present in marine organisms and the biological activity of the carotenoids, carotenoids of the muscles and tunic of tunicates and shellfishes were isolated and identified. Anitmutagenic activities of the carotenoids for S. typhimurium TA 98 and cytotoxic activity for cancer cell lines were determined. Total carotenoid contents in the muscle of tunicata ranged from 18.65 mg% to 2.39 mg%. The highest amount of the total carotenoid was found in the muscle of Halocynthia aurantium, followed by Styela clava (HERDMAN), H. roretzi, H. hilgendorfi f. igaboya, H. hilgendorfi f. retteri, S. plicata (LESUEUR) in order. Interestingly, total carotenoid content in the muscle of S. clava (HERDAMAN) was higher than that of H. roretzi. Total carotenoid content of all tunicata, other than H. aurantium and H. roretzi, were higher in muscle than tunic. The major carotenoids in H. roretzi, H. aurantium, S. plicata (LESUEUR), and S. clava (HERDAMAN) were cynthiaxanthin (25.1∼42.2%), halocynthiaxanthin (9.7∼26.3%), diatoxanthin (8.0∼18.7%) and β-carotene (7.7%∼21.7%). Similarly, cantaxanthin (19.6%), cynthiaxanthin (15.4%), halocynthiaxanthin (14.8%), and (3R, 3'R), (3S, 3'S)-astaxanthin (22.6%) in H. hilgendorfi f. retteri and fucoxanthin (26.6%), cynthiaxanthin (21.8%), halocynthiaxanthin (15.2%), and β-carotene (9.3%) in H. hilgendorfi f. igaboya were major carotenoids in both tunicate. However, the composition of carotenoids in muscle and tunic of tunicata was similar each other. Among the shellfishes examined, total carotenoid content of the muscle of Peronidia venulosa (Schrenck) and Corbicula fluminea, and of the gonad of Atrina pinnata and Chlamys farreri, was ranged from 2.51 to 6.83 mg% which were relatively higher than that of other shellfishes. The composition of the carotenoids of shellfishes, which might depend upon their living environments, was varied. But cynthiaxanthin (15.9∼39.0%) and zeaxanthin (9.6∼21.9%) in gonad of C. farreri, and muscles of Buccinum Volutharpa perryi (JAY) and Crassostrea gigas, cynthiaxanthin (21.5∼48.6%) and mytiloxanthin (14.6%) in muscle of C.fluminea and gonad of A. pinnata, and canthaxanthin (60.6%) and isozeaxanthin (20.5%) in muscles of P. venulosa (Schrenck), and β-carotene (23.7%∼37.8%) and zeaxanthin (18.2∼20.4) in muscles of Semisulcospira libertina and Meretrix lusoria were major carotenoids. Interestingly, diester type-carotenoids were present along with free type-carotenoids in muscles of C. gigas. antimutagenic effect of the carotenoids isolated from tunicata and shellfishes against 2-amino-3-methylimidazol [4,5-f]quinoline (IQ) for S. typhimurium TA 98 was proportional to the amount (20, 50 and 100㎍/plate) treated. Mutagenicity of IQ was significantly reduced by astaxanthin, isozeaxanthin, mytiloxanthin and halocynthiaxanthin, whereas the mutagenicity of aflatoxin B₁(AFB₁) was significantly reduced by β-carotene, isozeaxanthin, and mytiloxnthin. Growth inhibition effect of carotenoids isolated from tunicata and shellfishes for cancer cell was proportional to the amount (5, 10, and 20㎍/plate) treated. The growth of HeLa cell by β-carotene, cynthiaxanthin, astaxanthin and halocynthiaxanthin, NCI-H87 cell by β-carotene, astaxanthin, cynthiaxanthin, and halocynthiaxanthin, HT-29 cell by β-carotene, cynthiaxanthin, mytiloxanthin and halocynthiaxanthin, and MG-63 cells by β-carotene, cynthiaxanthin, astaxanthin, canthaxanthin and halocynthiaxanthin were statistically reduced.

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Anti-Inflammatory Effect of Hot Water Extract of Aronia Fruits in LPS-Stimulated RAW 264.7 Macrophages (LPS 자극 RAW 264.7 대식세포에 있어서 아로니아 열매 열수 추출물의 항염증 효과)

  • Yang, Hui;Oh, Kwang-Hoon;Yoo, Yung Choon
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.44 no.1
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    • pp.7-13
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    • 2015
  • In this study, anti-inflammatory activity of hot water extract of Aronia fruits (AF-H) was examined. Pre-treatment with AF-H significantly inhibited production of nitric oxide (NO) and prostaglandin E-2 in a dose-dependent manner in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The inhibitory effect of AF-H on LPS-induced inflammation was also confirmed by down-regulation of inducible NO synthase as well as cyclooxygenase-2 protein expression. Furthermore, treatment with AF-H significantly inhibited secretion of inflammatory cytokines such as tumor-necrosis $factor-{\alpha}$ and interleukin-6. Signal transduction pathway studies further indicated that AF-H inhibited LPS-induced activation of nuclear $factor-{\kappa}B$, but not mitogen-activated protein kinase. Treatment with AF-H also partially protected against LPS-induced lethal shock in C57BL/6 mice, although its effect was not statistically significant. These results suggest that AF-H is a more promising nutraceutical or medicinal agent for inhibition of LPS-induced inflammation or inflammation-related diseases.