• Journal of Ginseng Research
• /
• 제36권1호
• /
• pp.86-92
• /
• 2012

The glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults. Despite combination treatments of radiation and chemotherapy, the survival periods are very short. Therefore, this study was conducted to assess the potential of ginsenoside $F_2$ (F2) to treat GBM. In in vitro experiments with glioblastoma cells U373MG, F2 showed the cytotoxic effect with $IC_{50}$ of 50 ${\mu}g/mL$ through apoptosis, confirmed by DNA condensation and fragmentation. The cell population of cell cycle sub-G1 as indicative of apoptosis was also increased. In xenograft model in SD rats, F2 at dosage of 35 mg/kg weight was intravenously injected every two days. This reduced the tumor growth in magnetic resonance imaging images. The immunohistochemistry revealed that the anticancer activity might be mediated through inhibition of proliferation judged by Ki67 and apoptosis induced by activation of caspase-3 and -8. And the lowered expression of CD31 showed the reduction in blood vessel densities. The expression of matrix metalloproteinase-9 for invasion of cancer was also inhibited. The cell populations with cancer stem cell markers of CD133 and nestin were reduced. The results of this study suggested that F2 could be a new potential chemotherapeutic drug for GBM treatment by inhibiting the growth and invasion of cancer.

• 혜화의학회지
• /
• 제12권1호
• /
• pp.11-26
• /
• 2003

Alzheimer's disease (AD) is characterized by amyloid deposition and associated loss of neunons in brain regions involved in learning and memory processes. Several causes of evidence support that the congnitive disturbance is closed associated with the deficit of cerebral acetylcholine neurotransmission, and the effect of carboxyl terminal 105 amino acid fragment (CT105) of the amyloid precursor protein (APP) on the gene expression of proinflammatory cytokines. We tested it on the scopolamine-induced amnesia model of the ICR mouse using the Morris water maze with repeated orally administration of 1st Green-Tea extract (200 mg/kg) and 2nd Green-Tea extract (200 mg/kg). The Green-Tea prevents impairment of learning and memory and neuronal loss in mouse models of cognitive disturbance and it demonstrated selectivity for inhibition of acetylcholinesterase (AChE). Furthermore, the repeated administration of Green-Tea, CT105-induced alzheimer's mouse model showed central cholinergic activity by ameliorates learning and memory impairment, and isolation of CD14 microglia showed significantly decreases intracellular release of the proinflammatory cytokines tumor necrosis factor-${\alpha}$, interleukin-$1{\beta}$ and reactive oxygen species (ROS). Because of its composite profile, oral therapeutic index and a prophylactic, Green-Tea is considered the better therapeutic candidate for the treatment of Alzheimer's disease.

• Investigative Magnetic Resonance Imaging
• /
• 제18권2호
• /
• pp.120-132
• /
• 2014

목적: 원발성 뇌종양환자에서 방사선 치료 후 추적 자기공명영상에서 새로 생긴 조영증강 뇌병변에 대해 종양재발과 지연성 방사선치료연관변화의 감별에 있어서 확산강조영상 (DWI), 역동적조영관류영상 (DSC PWI), 자화율강조영상 (SWI)의 진단적 가치를 서로 비교하고자 한다. 대상과 방법: 원발성 뇌종양으로 이전에 방사선치료를 받았던 환자 중, 방사선치료 종료 최소 1년 이후에 추적 자기공명영상에서 새롭게 조영증강 되는 병변을 가진 24명의 환자를 대상으로 연구하였다. 새롭게 조영증강 되는 병변은 14명의 종양재발과 10명의 방사선치료연관변화로 확인되었다. 종양재발과 방사선치료연관변화 두 환자 군의 여러변수들은 비대응표본 t 검정을 실시하여 비교 분석하였다. 다중변수 로지스틱 회귀 분석을 이용하여 DWI, DSC PWI, SWI 각 영상의 정량 분석을 통해 얻은 apparent diffusion coefficient (ADC), normalized cerebral blood volume (nCBV), proportion of dark signal intensity (proSWI) 값 중 두 군을 감별해 내는 최상의 예측 변수 (best predictor)를 정하였다. 이후 수신자 조작 특성 (Receiver operating characteristics, ROC) 분석을 통하여 best predictor의 정확도, 민감도, 특이도를 평가하였다. 결과: 방사선치료연관변화 군과 비교하여 종양재발 군에서 평균 nCBV 값이 유의하게 높았고 (P=.004), 평균 proSWI 값은 유의하게 낮았다 (P<.001). 반면, 평균 ADC 값은 두 군간에 유의한 차이를 보이지 않았다. 다중변수 로지스틱 회귀 분석 결과 proSWI 값만이 통계적으로 유의한, 감별 가능한 독립변수였으며, 민감도, 특이도, 정확도는 각각 78.6% (11 of 14), 100% (10 of 10), 87.5% (21 of 24) 였다. 결론: 뇌종양 환자에서 방사선치료 종료 최소 1년 이후에 새로 보이는 조영증강 병변의 감별에 있어 proSWI 값이 가장 중요한 변수인 것으로 나타났다.

• Journal of Ginseng Research
• /
• 제45권3호
• /
• pp.433-441
• /
• 2021

Background: Multiple sclerosis (MS) and its animal model, the experimental autoimmune encephalomyelitis (EAE), are primarily characterized as dysfunction of the blood-brain barrier (BBB). Ginsenoside-Rg3-enriched Korean Red Ginseng extract (Rg3-KRGE) is known to exert neuroprotective, anti-inflammatory, and anti-oxidative effects on neurological disorders. However, effects of Rg3-KRGE in EAE remain unclear. Methods: Here, we investigated whether Rg3-KRGE may improve the symptoms and pathological features of myelin oligodendroglial glycoprotein (MOG)_35-55 peptide - induced chronic EAE mice through improving the integrity of the BBB. Results: Rg3-KRGE decreased EAE score and spinal demyelination. Rg3-KRGE inhibited Evan's blue dye leakage in spinal cord, suppressed increases of adhesion molecule platelet endothelial cell adhesion molecule-1, extracellular matrix proteins fibronection, and matrix metallopeptidase-9, and prevented decreases of tight junction proteins zonula occludens-1, claudin-3, and claudin-5 in spinal cord following EAE induction. Rg3-KRGE repressed increases of proinflammatory transcripts cyclooxygenase-2, inducible nitric oxide synthase, interleukin (IL)-1 beta, IL-6, and tumor necrosis factor-alpha, but enhanced expression levels of anti-inflammatory transcripts arginase-1 and IL-10 in the spinal cord following EAE induction. Rg3-KRGE inhibited the expression of oxidative stress markers (MitoSOX and 4-hydroxynonenal), the enhancement of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) and NOX4, and NADPH activity in the spinal cord of chronic EAE mice. Furthermore, apocynin, a NOX inhibitor, mimicked beneficial effects of Rg3-KRGE in chronic EAE mice. Conclusion: Our findings suggest that Rg3-KRGE might alleviate behavioral symptoms and pathological features of MS by improving BBB integrity through modulation of NOX2/4 expression.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권5호
• /
• pp.1839-1843
• /
• 2015

Background: MicroRNAs are a class of noncoding RNAs which regulate multiple cellular processes during tumor development. The purpose of this report is to investigate the clinicopathological and prognostic significance of miR-218 in human gliomas. Materials and Methods: Quantitative RT-PCR (qRT-PCR) was conducted to detect the expression of miR-218 in primary normal human astrocytes, three glioma cell lines and 98 paired glioma and adjacent normal brain tissues.Associations of miR-218 with clinicopathological variables of glioma patients were statistically analyzed. Finally, a survival analysis was performed using the Kaplan-Meier method and Cox's proportional hazards model. Results: The expression level of miR-218 in primary normal human astrocytes was significantly higher than that in glioma cell lines (p<0.01). Also, the expression level of miR-218 in glioma tissues was significantly downregulated in comparison with that in the adjacent normal brain tissues (p<0.001). Statistical analyses demonstrated that low miR-218 expression was closely associated with advanced WHO grade (p=0.002) and low Karnofsky performance score (p=0.010) of glioma patients. Kaplan-Meier analysis with the log-rank test showed that patients with low-miR-218 expression had poorer disease-free survival and overall survival (p=0.0045 and 0.0124, respectively). Multivariate analysis revealed that miR-218 expression was independently associated with the disease-free survival (p=0.009) and overall survival (p=0.004) of glioma patients. Conclusions: Our results indicate that miR-218 is downregulated in gliomas and that its status might be a potential valuable biomarker for glioma patients.

• Biomolecules & Therapeutics
• /
• 제21권5호
• /
• pp.381-390
• /
• 2013

The purpose of this study was to examine whether ginsenoside Rg3 (GRg3) could improve learning and memory impairments and inflammatory reactions induced by injecting lipopolysaccharide (LPS) into the brains of rats. The effects of GRg3 on proinflammatory mediators in the hippocampus and the underlying mechanisms of these effects were also investigated. Injection of LPS into the lateral ventricle caused chronic inflammation and produced deficits in learning in a memory-impairment animal model. Daily administration of GRg3 (10, 20, and 50 mg/kg, i.p.) for 21 consecutive days markedly improved the LPS-induced learning and memory disabilities demonstrated on the step-through passive avoidance test and Morris water maze test. GRg3 administration significantly decreased expression of pro-inflammatory mediators such as tumor necrosis factor-${\alpha}$, interleukin-1${\beta}$, and cyclooxygenase-2 in the hippocampus, as assessed by reverse transcription-polymerase chain reaction analysis and immunohistochemistry. Together, these findings suggest that GRg3 significantly attenuated LPS-induced cognitive impairment by inhibiting the expression of pro-inflammatory mediators in the rat brain. These results suggest that GRg3 may be effective for preventing or slowing the development of neurological disorders, including Alzheimer's disease, by improving cognitive and memory functions due to its anti-inflammatory activity in the brain.

• 한방재활의학과학회지
• /
• 제31권4호
• /
• pp.1-11
• /
• 2021

Objectives Hwanggeumjakyak-tang (HJT) has traditionally been used to treat gastrointestinal inflammatory diseases; however, its protective effects against neuronal inflammation are still undiscovered. Methods We investigated the anti-neuroinflammatory effects of HJT water extract on lipopolysaccharide (LPS)-stimulated BV2 mouse microglia cells. BV2 cells were treated with LPS (1 ㎍/mL) 1 hour prior to the addition of HJT. We measured cell viability using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and nitrite production using the Griess assay. We performed a reverse transcription-polymerase chain reaction assay to measure messenger RNA expression of inflammatory cytokines including interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. Western blot analysis was performed to determine protein expression of mitogen-activated protein kinases (MAPKs) and inhibitor of nuclear factor kappa B (NF-κB)α. Results HJT inhibited excessive nitrite release in LPS-stimulated BV2 cells and also significantly inhibited inflammatory cytokines such as IL-1β, IL-6, and TNF-α in LPS-stimulated BV2 cells. Moreover, HJT significantly suppressed LPS-induced MAPK and NF-κB activation and inhibited the elevation of IL-1β, IL-6, and TNF-α in the brain of LPS-injected mice. Conclusions Our study highlights the anti-neuroinflammatory effects of HJT via MAPK and NF-κB deactivation.

• BMB Reports
• /
• 제55권6호
• /
• pp.281-286
• /
• 2022

Hepatocellular carcinoma is a major health burden, and though various treatments through much research are available, difficulties in early diagnosis and drug resistance to chemotherapy-based treatments render several ineffective. Cancer stem cell model has been used to explain formation of heterogeneous cell population within tumor mass, which is one of the underlying causes of high recurrence rate and acquired chemoresistance, highlighting the importance of CSC identification and understanding the molecular mechanisms of CSC drivers. Extracellular CSC-markers such as CD133, CD90 and EpCAM have been used successfully in CSC isolation, but studies have indicated that increasingly complex combinations are required for accurate identification. Pseudogene-derived long non-coding RNAs are useful candidates as intracellular CSC markers - factors that regulate pluripotency and self-renewal - given their cancer-specific expression and versatile regulation across several levels. Here, we present the use of microarray data to identify stemness-associated factors in liver cancer, and selection of sole pseudogene-derived lncRNA ZNF204P for experimental validation. ZNF204P knockdown impairs cell proliferation and migration/invasion. As the cytosolic ZNF204P shares miRNA binding sites with OCT4 and SOX2, well-known drivers of pluripotency and self-renewal, we propose that ZNF204P promotes tumorigenesis through the miRNA-145-5p/OCT4, SOX2 axis.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권19호
• /
• pp.8483-8488
• /
• 2014

Background: Breast cancer is the most common cancer and the second most common cause of cancer-induced mortalities in Iranian women, following gastric carcinoma. The survival of these patients depends on several factors, which are very important to identify in order to understand the natural history of the disease. Materials and Methods: In this retrospective study, 313 consecutive women with pathologically-proven diagnosis of breast cancer who had been treated during a seven-year period (January 2006 until March 2014) at Towhid hospital, Sanandaj city, Kurdistan province of Iran, were recruited. The Kaplan-Meier method was used for data analysis, and finally those factors that showed significant association on univariate analysis were entered in a Cox regression model. Results: the mean age of patients was $46.10{\pm}10.81$ years. Based on Kaplan-Meier method median of survival time was 81 months and 5 year survival rate was $75%{\pm}0.43$. Tumor metastasis (HR=9.06, p=0.0001), relapse (HR=3.20, p=0.001), clinical stage of cancer (HR=2.30, p=0.03) and place of metastasis (p=0.0001) had significant associations with the survival rate variation. Patients with tumor metastasis had the lowest five-year survival rate (37%)and among them patients who had brain metastasis were in the worst condition (5 year survival rate= $11%{\pm}0.10$). Conclusions: Our findings support the observation that those women with higher stages of breast malignancies (especially with metastatic cancer) have less chance of surviving the disease. Furthermore, screening programs and early detection of breast cancer may help to increase the survival of those women who are at risk of breast cancer.

• 동의신경정신과학회지
• /
• 제12권2호
• /
• pp.157-171
• /
• 2001

Astrocytes are glial cells that play a major role in the inflammation observed in Alzheimer's disease (AD). Upon stimulation from various agents, these cells adopt a reactive phenotype, a morphological hallmark in AD pathology, during which they themselves may produce still more inflammatory cytokines. Substance P (SP) can stimulate secretion of tumor necrosis $factor-\;{\alpha}$ $(TNF-\;{\alpha})$ from astrocytes stimulated with lipopolysaccharide (LPS). Here I report that Sunghyangjungkisan- ga- pogokyoung(Sgp) can modulate cytokines secretion from primary cultures of rat astrocytes. Sgp $(10\;to\;1000\;{\mu}g/ml)$ significantly inhibited the $TNF-\;{\alpha}$ secretion by astrocytes stimulated with LPS and SP. Interleukin-1 (IL-1) has been shown to elevate $TNF-\;{\alpha}$ secretion from LPS-stimulated astrocytes while having no effect on astrocytes in the absence of LPS. Treatment of Sgp $(10\;to\;1000\;{\mu}g/ml)$ to astrocytes stimulated with both LPS and SP decreased IL-1 secretion significantly. The secretion of $TNF-\;{\alpha}$ by LPS and SP in astrocytes was progressively inhibited with increasing amount of IL-1 neutralizing antibody. Neurodegenerative processes in AD are thought to be driven in part by the deposition of ${\beta}\;-amyloid\;(A\;{\beta})$, a 39- to 43-amino acid peptide product resulting from an alternative cleavage of amyloid precursor protein. Sgp $(10\;to\;1000\;{\mu}g/ml)$ significantly inhibited the $TNF-\;{\alpha}$ secretion by astrocytes stimulated with $A-{\beta}-$and IL-1. These results suggest that Sgp may inhibit $TNF-\;{\alpha}$ secretion by inhibiting IL-1 secretion and that Sgp has an antiinflammatory activity in AD brain