• Toxicological Research
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• 제31권1호
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• pp.11-16
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• 2015

Our body's immune system has defense mechanisms against pathogens such as viruses and bacteria. Immune responses are primarily initiated by the activation of toll-like receptors (TLRs). In particular, TLR4 is well-characterized and is known to be activated by gram-negative bacteria and tissue damage signals. TLR4 requires myeloid differentiation factor 2 (MD2) as a co-receptor to recognize its ligand, lipopolysaccharides (LPS), which is an extracellular membrane component of gram-negative bacteria. Gambogic acid is a xanthonoid isolated from brownish or orange resin extracted from Garcinia hanburyi. Its primary effect is tumor suppression. Since inflammatory responses are related to the development of cancer, we hypothesized that gambogic acid may regulate TLR4 activation. Our results demonstrated that gambogic acid decreased the expression of pro-inflammatory cytokines ($TNF-{\alpha}$, IL-6, IL-12, and $IL-1{\beta}$) in both mRNA and protein levels in bone marrow-derived primary macrophages after stimulation with LPS. Gambogic acid did not inhibit the activation of Interferon regulatory factor 3 (IRF3) induced by TBK1 overexpression in a luciferase reporter gene assay using IFN-${\beta}$-PRD III-I-luc. An in vitro kinase assay using recombinant TBK1 revealed that gambogic acid did not directly inhibit TBK1 kinase activity, and instead suppressed the binding of LPS to MD2, as determined by an in vitro binding assay and confocal microscopy analysis. Together, our results demonstrate that gambogic acid disrupts LPS interaction with the TLR4/MD2 complex, the novel mechanism by which it suppresses TLR4 activation.

• Journal of Ginseng Research
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• 제24권2호
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• pp.79-82
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• 2000

사포닌은 인삼의 약리작용을 매개하는 인삼의 주요 성분이다. 인삼의 뿌리는 여러 가지 독소에 의하여 유발되는 독성에 대한 보호작용이 있는 것으로 알려지고 있다. 본 연구에서는 세균독소(lipopolysaccharides)에 의하여 유도되는 종양괴사인자 생성에 미치는 인삼 사포닌의 영향을 살펴보았다. 독소를 투여한 생쥐의 혈청중 종양괴사인자의 농도는 상승하는데, 인삼 사포닌 50 mg/kg을 독소와 함께 복강으로 투여한 경우는 독소만 투여하였을 때에 비하여 혈정 중 종양괴사인자의 농도가 현저히 낮았다. 이러한 인삼 사포닌의 효과는 사포닌의 용량, 투여방법과 투여시간에 영향을 받았는데, 사포닌을 경구로 투여하거나 독소를 주사한 후에 투여하였을 때에는 종양괴사인자 농도에 유의성 있는 차이를 나타내지 않았다. 이러한 결과는 인삼이 간 손상에 대한 보호작용이 있을 가능성을 시사하였고, 사포닌이 이러한 인삼의 보호효과를 매개하는 활성 성분임을 의미한다.

• 치위생과학회지
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• 제20권4호
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• pp.213-220
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• 2020

Background: The leaves of Perilla frutescens, commonly called perilla and used for food in Korea, contain components with a variety of biological effects and potential therapeutic applications. The purpose of this study was to identify the components of 70% ethanol extracted Perilla frutescens (EEPF) and determine its inhibitory effects on oral microbial activity and production of nitric oxide (NO) and prostaglandin E2 (PGE2) in lipopolysaccharides (LPS)-stimulated Raw264.7 macrophages, consequently, to confirm the possibility of using EEPF as a functional component for improving the oral environment and preventing inflammation. Methods: One kg of P. frutescens leaves was extracted with 70% ethanol and dried at -70℃. EEPF was analyzed using high-performance liquid chromatography analysis, and antimicrobial activity against oral microorganisms was revealed using the disk diffusion test. Cell viability was elucidated using a methylthiazolydiphenyl-tetrazolium bromide assay, and the effect of EEPF on LPS-induced morphological variation was confirmed through microscopic observation. The effect of EEPF on LPS-induced production of pro-inflammatory mediators, NO and PGE2 was confirmed by the NO assay and PGE2 enzyme-linked immunosorbent assay. Results: The main component of EEPF was rosemarinic acid, and EEPF showed weak anti-bacterial and anti-fungal effects against microorganisms living in the oral cavity. EEPF did not show toxicity to Raw264.7 macrophages and had inhibitory effects on the morphological variations and production of pro-inflammatory mediators, NO and PGE2 in LPS-stimulated Raw264.7 macrophages. Conclusion: EEPF can be used as a functional material for improving the oral environment through the control of oral microorganisms and for modulating inflammation by inhibiting the production of inflammatory mediators.

• 한국발생생물학회지:발생과생식
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• 제26권4호
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• pp.135-144
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• 2022

As the number of coronavirus disease 2019 (COVID-19) vaccinations increases, various side effects are being reported, and menstrual abnormalities have been reported as a side effect in women. However, it is still unclear whether the COVID-19 vaccine has detrimental effects on the female reproductive system. Therefore, we investigated the effect of excessive immune response on reproductive function by administering Lipopolysaccharides (LPS) instead of the COVID-19 vaccine. The immune response in mice was induced by injection of LPS. Mice injected with saline 5 times were used as a control group, and mice injected with LPS 5 times were used as an experimental group. Repeated administration of LPS significantly reduced the number of corpus luteum (CL). On the other hand, the injection of LPS did not affect the development of follicles leading before the CL. The expression of the apoptosis-related genes Fas and Fas-L increased in the experimental group. In addition, the expression of the inflammation-related genes increased in the experimental group. In this study, we confirmed that LPS had detrimental effects on the uterus and ovaries in mice. These results suggest that injection of LPS can cause immune reactions within the uterus and ovaries and cause hormonal changes, which can have adverse effects such as abnormal operation or bleeding of the menstrual cycle. These results are expected to help determine the cause of decreased reproductive function, infertility, or physiological disorders caused by the COVID-19 vaccine.

• 한국해양바이오학회지
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• 제15권2호
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• pp.33-40
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• 2023

This study aimed to investigate the immunomodulatory function of Pyropia yezoensis hydrothermal (water) extract (PYWE) in comparison to the group treated only with lipopolysaccharides (LPS) in RAW264.7 cells. LPS is known to be an inflammatory mediator that activates macrophages, leading to the secretion of nitric oxide (NO), inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) as defense responses. Through enzyme-linked immunoassay and western blot analyses, it was observed that PYWE increased the expression levels of NO, iNOS, TNF-α, and IL-6 in RAW264.7 cells in a dose-dependent manner, although to a lesser extent compared with the group treated with LPS alone. In addition, the study examined the mitogen-activated protein kinases (MAPKs) pathway, which regulates various cellular activities, including gene expression, mitosis, cell differentiation, transformation, survival, and death. The western blot analysis confirmed that PYWE also regulated the MAPKs pathway. Furthermore, the expression levels of immunomodulatory-related factors increased in the group treated with PYWE compared with the control group. Even though the effects of PYWE were usually less strong than those of LPS, the effects of PYWE increased with increasing doses compared to the control group. This suggests that PYWE could be used to control the immune system.

• 대한치주과학회:학술대회논문집
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• 대한치주과학회 2005년도 제45회 종합학술대회 연제초록
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• pp.87-88
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• 2005

• Journal of Microbiology and Biotechnology
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• 제16권8호
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• pp.1292-1300
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• 2006

Aeromonas encheleia, a potential human intestinal pathogen, was shown to infect a human intestinal epithelial cell line (Caco-2) in a noninvasive manner. The transcriptional profile of the Caco-2 cells after infection with the bacteria revealed an upregulated expression of genes involved in chloride secretion, including that of phospholipase A2 (PLA2) and platelet-activating factor (PAF) acetylhydrolase (PAFAH2). This was also confirmed by a real-time RT-PCR analysis. As expected from PLA2 induction, PAF was produced when the Caco-2 cells were infected with the bacteria, and PAF was also produced when the cells were treated with a bacterial culture supernatant including bacterial extracellular proteins, yet lacking lipopolysaccharides. Bacterial aerolysin was shown to induce the production of PAF.

• Natural Product Sciences
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• 제15권2호
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• pp.55-59
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• 2009

This study for developing a new anti-inflammatory medicine was sought by investigating the antiinflammatory properties of C. indicum L. extract. Rats were treated with either saline (control) or C. indicum L. extract and then injected with LPS. We found that the plasma concentration of IL-1${\beta}$ IL-6, TNF-${\alpha}$and IL-10 peaked at 5h after LPS injection, and the plasma concentration of IL-6 and TNF-${\alpha}$ showed a tendency to decrease, and IL-10 concentration showed a tendency to increase with increasing levels of C. indicum L. extract. In the liver concentration of cytokines at 5 h post LPS injection, IL-1${\alpha}$ and IL-6 decreased with increasing concentration of C. indicum L. extract, however TNF-${\alpha}$ and IL-10 did not differ significantly the treatment groups.

• Biomolecules & Therapeutics
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• 제12권3호
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• pp.133-137
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• 2004

Present review is built on base of research work on Ganoderma lucidum in our laboratory. A great deal of experimental evidence has suggested that the pharmacological activities of Ganoderma lucidum (Lingzhi) are related to anti-oxidative and free radical scavenging activity. The anti-oxidative and free radical scavenging effects of polysaccharides and triterpenoids isolated from Ganoderma lucidum in different oxidative injury models including tert-butylhydroperoxide (tBOOH)- damaged mice peritoneal macrophages, alloxan-induced diabetes, experimental liver injury models induced by carbon tetrachloride (CCl4), D-galactosamine (DGal) and Bacillus Calmette-Guerin (BCG) plus lipopolysaccharides (LPS) were investigated. It is also demonstrated that Lugu lingzhi, one of Ganoderma product, significantly inhibited LDL oxidation mediated by endothelial cells and decreased monocyte adhesion to endothelial cell (EC) induced by Oxidative low-density lipoprotein (ox-LDL) and advanced glycation endproducts (AGE). Lugulingzhi-treated serum could markedly inhibit the expression of intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-l) induced by ox-LDL and AGE.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2004년도 Annual Meeting of KSAP : New Drug Development from Natural Products
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• pp.61-77
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• 2004

Present review is built on base of research work on Ganoderma lucidum in our laboratory. A great deal of experimental evidence has suggested that the pharmacological activities of Ganoderma lucidum(Lingzhi) are related to anti-oxidative and free radical scavenging activity. The anti-oxidative and free radical scavenging effects of polysaccharides and triterpenoids isolated from Ganoderma lucidum in different oxidative injury models including tert-butylhydroperoxide (tBOOH)- damaged mice peritoneal macrophages, alloxan-induced diabetes, experimental liver injury models induced by carbon tetrachloride (CC14), D-galactosamine (DGal) and Bacillus Calmette-Guerin(BCG) plus lipopolysaccharides(LPS) were investigated. It is also demonstrated that Lugu lingzhi, one of Ganoderma product, significantly inhibited LDL oxidation mediated by endothelial cells and decreased monocyte adhesion to endothelial cell (EC) induced by Oxidative low-density lipoprotein (ox-LDL) and advanced glycation endproducts(AGE). Lugulingzhi-treated serum could markedly inhibit the expression of intercellular cell adhesion molecule-l (ICAM-1) and vascular cell adhesion molecule-l (VCAM-1) induced by ox-LDL and AGE.