• Title/Summary/Keyword: cytotoxicity-enhancing effects

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Gastroprotective effects of the nonsaponin fraction of Korean Red Ginseng through cyclooxygenase-1 upregulation

  • Lee, Jeong-Oog;Kim, Ji Hye;Kim, Sunggyu;Kim, Mi-Yeon;Hong, Yo Han;Kim, Han Gyung;Cho, Jae Youl
    • Journal of Ginseng Research
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    • v.44 no.4
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    • pp.655-663
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    • 2020
  • Background: Korean Red Ginseng is known to exhibit immune-enhancing and anti-inflammatory properties. The immune-enhancing effects of the nonsaponin fraction (NSF) of Korean Red Ginseng have been studied in many reports. However, the gastroprotective effect of this fraction is not fully understood. In this study, we demonstrate the activities of NSF for gastrointestinal protection and its related critical factor. Methods: The in vitro and in vivo regulatory functions of NSF on cyclooxygenase-1 (COX-1) messenger RNA and protein levels were examined by reverse transcription polymerase chain reaction and immunoblotting analyses. Gastroprotective effects of NSF were investigated by histological score, gastric juice pH, and myeloperoxidase activity on indomethacin-induced, cold stress-induced, and acetylsalicylic acid-induced gastritis and dextran sulfate sodium-induced colitis in in vivo mouse models. Results: NSF did not show cytotoxicity, and it increased COX-1 messenger RNA expression and protein levels in RAW264.7 cells. This upregulation was also observed in colitis and gastritis in vivo models. In addition, NSF treatment in mice ameliorated the symptoms of gastrointestinal inflammation, including histological score, colon length, gastric juice pH, gastric wall thickness, and myeloperoxidase activity. Conclusion: These results suggest that NSF has gastroprotective effects on gastritis and colitis in in vivo mouse models through COX-1 upregulation.

Combination Doxorubicin and Interferon-α Therapy Stimulates Immunogenicity of Murine Pancreatic Cancer Panc02 Cells via Up-regulation of NKG2D ligands and MHC Class I

  • Wang, Wen-Jia;Qin, Si-Hao;Zhang, Ji-Wei;Jiang, Yue-Yao;Zhang, Jin-Nan;Zhao, Lei
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.22
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    • pp.9667-9672
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    • 2014
  • Background: Pancreatic adenocarcinoma is a malignant gastrointestinal cancer with significant morbidity and mortality. Despite severe side effects of chemotherapy, the use of immunotherapy combined with chemotherapy has emerged as a common clinical treatment. In this study, we investigated the efficacy of the combined doxorubicin and interferon-${\alpha}$ (IFN-${\alpha}$) therapy on murine pancreatic cancer Panc02 cells in vitro and in vivo and underlying mechanisms. Materials and Methods: A Panc02-bearing mouse model was established to determine whether doxorubicin and interferon-${\alpha}$ (IFN-${\alpha}$) could effectively inhibit tumor growth in vivo. Cytotoxicity of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs) was evaluated using a standard LDH release assay. To evaluate the relevance of NK cells and CD8 T cells to the combination therapy-mediated anti-tumor effects, they were depleted in tumor-bearing mice by injecting anti-asialo-GM-1 antibodies or anti-CD8 antibodies, respectively. Finally, the influence of doxorubicin+interferon-${\alpha}$ (IFN-${\alpha}$) on the ligands of NK and T cells was assessed by flow cytometry. Results: The combination therapy group demonstrated a significant inhibition of growth of Panc02 in vivo, resulting from activated cytotoxicity of NK cells and CTLs. Depleting CD8 T cells or NK cells reduced the anticancer effects mediated by immunochemotherapy. Furthermore, the doxorubicin+IFN-a treatment increased the expression of major histocompatibility complex class I (MHC I) and NKG2D ligands on Panc02 cells, suggesting that the combined therapy may be a potential strategy for enhancing immunogenicity of tumors. All these data indicate that the combination therapy using doxorubicin and interferon-${\alpha}$ (IFN-${\alpha}$) may be a potential strategy for treating pancreatic adenocarcinoma.

Biological Effects of the Leaves and Roots of Ligularia stenocephala (곤달비 잎과 뿌리의 생물 활성)

  • Nam, Young-Joo;Lee, Dong-Ung
    • Journal of Life Science
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    • v.23 no.11
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    • pp.1381-1387
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    • 2013
  • The leaves and roots of Ligularia stenocephala, which are widely used as a food in Korea, were investigated for their antioxidant activities and cytotoxicity in vitro, and their hepatoprotective effect, alcohol detoxicant efficacy, and memory-enhancing property were investigated in vivo. The unique odor of the leaves was analyzed by GC-MS. Lipid peroxidation, superoxide anion formation, and DPPH radicals were inhibited remarkably by the extracts of the leaves and roots. The leaves of this edible plant significantly protected the hepatotoxicity induced by carbon tetrachloride and further diminished the blood alcohol content in mice. While the roots of this plant exhibited adequate cytotoxicity against four human tumor cell lines, especially against melanoma, the leaves revealed relatively weak activity. Both the leaves and the roots exerted an excellent ameliorating property on scopolamine-induced memory impairment in the passive avoidance task using an animal model. The hexane fraction of the leaves was analyzed by GC-MS, suggesting that a series of terpenoids may be odorous compounds in this plant.

Effects of BuOH Extract of the Root of Aralia elata as an Absorption Enhancer on the Transport of Chondroitin Sulfate and Its Digestion Products In Vitro and In Vivo

  • Sim, Joon-Soo;Li, Da-Wei;Cho, Hai-Lim;Cho, So-Yean;Jeong, Choon-Sik;Lee, Eun-Bang;Kim, Yeong-Shik
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.415.2-415.2
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    • 2002
  • We investigated the absorption enhancing effect of BuOH extract of the root of Aralia elata (BERAE) in Caco-2 cell monolayers and rats. At the concentration of both 0.04% and 0.08% (w/v). BERAE decreased the transepithelial electrical resistance (TEER) values and increased the permeability of intact chondroitin sulfate (CS) and its digestion products as hydrophilic macromolecules in a dose dependent manner. We also evaluated the cytotoxicity of BERAE for the determination of a proper concentration as an absorption enhancer. (omitted)

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Immune Enhancing Effects of Intracellular and Extracellular Polysaccharides Extracted from Mycelial Cultivate of Agaricus blazei Murill (신령버섯(Agaricus blazei Murill) 균사체내외 다당체의 면역활성효과)

  • Kim, Moo-Sung;Cho, Hong-Bum
    • Korean Journal of Microbiology
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    • v.43 no.4
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    • pp.292-297
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    • 2007
  • This study was performed to compare in vitro immune enhancing effects of polysaccharides extracted from cultivated mycelia of Agaricus blazei Murill. Carbohydrate contents of semi-purified polysaccharides were 85.6% and 95.3%, while ${\beta}$-glucan conents were 67.9% and 88.1% for intracellular and extracellular polysaccharide, respectively. Samples were adjusted to the same in their carbohydrate contents before efficacy tests. Both intracellular and extracellular polysaccharide increased nitric oxide (NO) synthesis of macrophage RAW 264.7 in dose dependent manner, and the maximum increase rate was 53.9 and 53.1% in intracellular and extraceltular polysaccharide, respectively. The polysaccharides also increased synthesis of cytokines such as interleukin (IL)-$1{\beta}$, IL-6 and tumor necrosis factor (TNF)-${\alpha}$ in RAW 264.7. For all the 3 cytokines, the increase rate of synthesis was much higher in extracellular polysaccharide compared to intracellular polysaccharide, especially at low concentration. Both polysaccarides increased the proliferation of splenocytes in vitro, intracellular polysaccharide showed increase in dose dependent manner while extraceltular polysaccharide showed increase untill medium concentration ($250\;{\mu}g/ml$). They did not show direct cytotoxicity against cancer cells such as B16F0 melanoma. As results, it was regarded that the both intracellular and extracellular polysaccharide from A. blazei showed immune enhancing effects in vitro, but the activity is higher in extracellular polysaccharide compared to intracellular polysaccharide.

Investigation of the effect of water extract from Cudrania tricuspidata fruit on tight junction in human keratinocyte (꾸지뽕 열매 추출물이 인간 유래 각질 형성 세포의 밀착연접에 미치는 영향)

  • Lee, Sang Soo;Choi, Sun Kyung;Kim, Jae Whan;Han, Hyo Sang;Kim, Kee Kwang
    • The Korea Journal of Herbology
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    • v.34 no.1
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    • pp.99-107
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    • 2019
  • Objectives : Cudrania tricuspidata (C. tricuspidata) is well-known traditional herbal remedy and its root, leaf and fruit were used for treatment of inflammation, tumor and painkilling. However, effect of C. tricuspidata fruit on tight junction is still unknown. The aim of this research was to determine the effect of C. tricuspidata fruit extract on human keratinocyte HaCaT cells. Methods : The antioxidant effects of water extract of C. tricuspidata (WECT) and ethanol extract of C. tricuspidata (EECT) were analyzed by using an ABTS assay. To confirm the cytotoxicity of WECT and EECT, MTS assay was performed. The mRNA expression levels of tight junction related genes were analyzed using quantitative RT-PCR analysis. Furthermore, dispase assay was used to investigate the alteration of cell-cell adhesion strength of EECT treated HaCaT cells. Results : WECT and EECT showed strong antioxidant activity. No obvious cytotoxicity was observed in both WECT and EECT until $2.0mg/m{\ell}$ concentration. The mRNA expression level of Claudin 6 were significantly increased by EECT treatment, whereas the WECT did not affect the expression of Claudin 6. Furthermore, EECT treatment enhances cell-cell adhesion strength. Conclusions : In this study, we investigated the physiological activities of the extracts of Cudrania tricuspidata fruit extracts on human keratinocytes by two different extraction methods. EECT might have an anti-aging activity on the skin by reducing oxidative stress. Moreover, it may be a useful ingredient in atopic dermatitis and skin-moisturizing, given its effects of altering Claudin 6 gene expression and enhancing cell-cell adhesion strength.

A Study on The Raw Materials Standardization for Industrialization of Zanthoxylum piperitum Using Lava Seawater

  • Eun Bi Jang;Hyejin Hyeon;Yoonji Lee;Sung Hye Han;Kwang Yeol Baek;Su Young Jung;Ki Sung Shin;Weon-Jong Yoon
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2023.04a
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    • pp.61-61
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    • 2023
  • Zanthoxylum piperitum has been used as a spice or various folk remedies since ancient times, and studies on antibacterial, anti-inflammatory and analgesic effects have been reported. In this study, a raw material standardization study was conducted for the industrialization of Z. piperitum. First, optimal conditions for drying methods were established for the standardization of raw materials for Z. piperitum, and optimal conditions were established through content analysis using quercitrin, an marker compound, by obtaining samples every month. As for the drying method of Z. piperitum, it was confirmed that cold air drying was the best. It was analyzed that the marker compound content was highest in July. Next, for functional and toxicity evaluation of Z. piperitum, anti-oxidant, anti-inflammatory and immune enhancing efficacy and cytotoxicity were evaluated. Cytotoxicity of Z. piperitum was not observed, and it was confirmed that although it had an antioxidant and anti-inflammatory effect, it had no immuneenhancing effects. In addition, a study was conducted on the change in the efficacy of Z. piperitum using lava seawater, and as a result of the study, it was confirmed that the efficacy was superior when lava seawater was simultaneously treated. In conclusion, this study suggested the standardization of raw materials through the analysis of the marker compounds and the functional evaluation of Z. piperitum, and it can be used as basic data for future industrialization.

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Neuroprotective Effect of Chebulagic Acid via Autophagy Induction in SH-SY5Y Cells

  • Kim, Hee Ju;Kim, Joonki;Kang, Ki Sung;Lee, Keun Taik;Yang, Hyun Ok
    • Biomolecules & Therapeutics
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    • v.22 no.4
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    • pp.275-281
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    • 2014
  • Autophagy is a series of catabolic process mediating the bulk degradation of intracellular proteins and organelles through formation of a double-membrane vesicle, known as an autophagosome, and fusing with lysosome. Autophagy plays an important role of death-survival decisions in neuronal cells, which may influence to several neurodegenerative disorders including Parkinson's disease. Chebulagic acid, the major constituent of Terminalia chebula and Phyllanthus emblica, is a benzopyran tannin compound with various kinds of beneficial effects. This study was performed to investigate the autophagy enhancing effect of chebulagic acid on human neuroblastoma SH-SY5Y cell lines. We determined the effect of chebulagic acid on expression levels of autophagosome marker proteins such as, DOR/TP53INP2, Golgi-associated ATPase Enhancer of 16 kDa (GATE 16) and Light chain 3 II (LC3 II), as well as those of its upstream pathway proteins, AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR) and Beclin-1. All of those proteins were modulated by chebulagic acid treatment in a way of enhancing the autophagy. Additionally in our study, chebulagic acid also showed a protective effect against 1-methyl-4-phenylpyridinium ($MPP^+$) - induced cytotoxicity which mimics the pathological symptom of Parkinson's disease. This effect seems partially mediated by enhanced autophagy which increased the degradation of aggregated or misfolded proteins from cells. This study suggests that chebulagic acid is an attractive candidate as an autophagy-enhancing agent and therefore, it may provide a promising strategy to prevent or cure the diseases caused by accumulation of abnormal proteins including Parkinson's disease.

Immune Enhancement Effects of Neutral Lipids, Glycolipids, Phospholipids from Halocynthia aurantium Tunic on RAW264.7 Macrophages

  • A-yeong Jang;Weerawan Rod-in;Il-shik Shin;Woo Jung Park
    • Journal of Microbiology and Biotechnology
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    • v.34 no.2
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    • pp.476-483
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    • 2024
  • Fractionated lipids of Halocynthia aurantium (Pyuridae) have been demonstrated to possess anti-inflammatory properties. However, their modulatory properties have not been reported yet. Thus, the objective of this study was to determine immune enhancing effects of fractionated lipids from H. aurantium tunic on macrophage cells. The tunic of H. aurantium was used to isolate total lipids, which were then subsequently separated into neutral lipids, glycolipids, and phospholipids. RAW264.7 cells were stimulated with different concentrations (0.5, 1.0, 2.0, and 4.0%) of each fractionated lipid. Cytotoxicity, production of NO, expression levels of immune-associated genes, and signaling pathways were then determined. Neutral lipids and glycolipids significantly stimulated NO and PGE2 production and expression levels of IL-1β, IL-6, TNF-α, and COX-2 in a dose-dependent manner, while phospholipids ineffectively induced NO production and mRNA expression. Furthermore, it was found that both neutral lipids and glycolipids increased NF-κB p-65, p38, ERK1/2, and JNK phosphorylation, suggesting that these lipids might enhance immunity by activating NF-κB and MAPK signaling pathways. In addition, H. aurantium lipids-induced TNF-α expression was decreased by blocking MAPK or NF-κB signaling pathways. Phagocytic activity of RAW 264.7 cells was also significantly enhanced by neutral lipids and glycolipids. These results suggest that neutral lipids and glycolipids from H. aurantium tunic have potential as immune-enhancing materials.

PAMAM Dendrimers Augment Inhibitory Effects of Curcumin on Cancer Cell Proliferation: Possible Inhibition of Telomerase

  • Mollazade, Mahdie;Nejati-Koshki, Kazem;Akbarzadeh, Abolfazl;Zarghami, Nosratollah;Nasiri, Marzieh;Jahanban-Esfahlan, Rana;Alibakhshi, Abbas
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.11
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    • pp.6925-6928
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    • 2013
  • Background: Despite numerous useful anticancer properties of curcumin, its utility is limited due to its hydrophobic structure. In this study, we investigated the comparative antiproliferative effect of PAMAM encapsulating curcumin with naked curcumin on the T47D breast cancer cell line. Materials and Methods: Cytotoxic effects of PAMAM dendrimers encapsulating curcumin and curcumin alone were investigated by MTT assay. After treating cells with different concentrations of both curcumin alone and curcumin encapsulated for 24h, telomerase activity was determined by TRAP assay. Results: While PAMAM dendrimers encapsulating curcumin had no cytotoxicity on cancer cells, they decreased the $IC_{50}$ for proliferation and also increased the inhibitory effect on telomerase activity. Conclusions: Considering the non-toxicity in addition to effectiveness for enhancing curcumin anticancer properties, dendrimers could be considered good therapeutic vehicles for this hydrophobic agent.