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

• 동의생리병리학회지
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• 제34권6호
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• pp.348-354
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• 2020

Oryeong-san (ORS) is a traditional Korean herbal medicine widely used for renal associated diseases, composed of five medicine herbs; Atractylodes japonica Koidzumi, Cinnamomum cassia Presl, Polyporus umbellatus Fries, Poria cocos Wolf and Alisma orientale Juzepzuk. We studied to improve the convenience of intake and portability by developing modernized dosage forms, and examined the effect on anti-inflammation of ORS. In order to develop the tablet formulation of ORS (ORS-F), the tablets were evaluated on the basis of physical characteristics include diameter, thickness, weight variation, hardness, friability and disintegration. To analyze the marker components of ORS-F, eight index markers from five herbal medicines were chosen. And the method using high performance liquid chromatography (HPLC) with diode-array detector method was established for the simultaneous analysis. The biological activities were examined the effect of ORS-F on pro-inflammation mediated by LPS-stimulation. The production of nitric oxide (NO) and cytokines were determined by reacting cultured medium with griess reagent and enzyme-linked immunosorbent assay (ELISA). The expression of cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS) were investigated by Western blot and RT-PCR. The anti-oxidant activities of OJS-F increased markedly, in a dose-dependent manner. and, The total phenolic compound and flavonoids contents of OJS-F were 10.20±0.09 ㎍/㎎ and 12.86±0.86 ㎍/㎎. OJS-F which is LPS has diminished in the LPS-induced release of inflammatory mediators (NO, iNOS, COX2 and PGE2) and pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β) from the RAW264.7 macrophages. Therefore, the developed formulation for tablet of ORS-F provide efficiency and usability, and indicated effect of anti-inflammation.

• IMMUNE NETWORK
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• 제22권4호
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• pp.35.1-35.16
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• 2022

Tobacco smoking (TS) has been known as one of the most potent risk factors for airway inflammatory diseases. However, there has been a paucity of information regarding the immunologic alteration mediated by TS in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). To identify the effect of TS, we harvested human tissue samples (never smoker: n=41, current smoker: n=22, quitter: n=23) and analyzed the expression of epithelial-derived cytokines (EDCs) such as IL-25, IL-33, and thymic stromal lymphopoietin. The expressions of Th2 cytokines and total serum IgE showed a type-2 inflammatory alteration by TS. In addition, the epithelial marker E-cadherin and epithelial-mesenchymal transition (EMT)-associated markers (N-cadherin, α-SMA, and vimentin) were evaluated. Histological analysis showed that EDC expressions were upregulated in the current smoker group and downregulated in the quitter group. These expression patterns were consistent with mRNA and protein expression levels. We also found that the local Th2 cytokine expression and IgE class switching, as well as serum IgE levels, were elevated in the current smoker group and showed normal levels in the quitter group. Furthermore, the expressions of E-cadherin decreased while those of N-cadherin, α-SMA, and vimentin increased in the current smoker group compared those in the never smoker group. Taken together, these results indicate that TS contributes to the deterioration of pathogenesis by releasing local EDCs and Th2 cytokines, resulting in EMT in patients with CRSwNP. We verified that alterations of immunological response by TS in sinonasal epithelium can play a vital role in leading to CRSwNP.

• Clinical and Experimental Pediatrics
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• 제49권9호
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• pp.987-990
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• 2006

정맥내 면역글로블린은 급성 가와사끼병의 치료에 효과적이나 약 10-20%의 환자에서 치료 실패가 보고되고 있다. 이러한 경우 면역글로블린의 재투여 또는 스테로이드나 다른 약제의 사용 등 다양한 치료방법이 시도되고 있으나 아직 이에 대한 확립된 치료 가이드라인은 없다. $TNF-{\alpha}$는 가와사끼병의 급성기, 특히 관상동맥류를 가진 환자에서 혈중농도가 크게 증가한다. 저자들은 2번의 면역글로블린 투여와 3번의 pulse methylprednisolone 치료에 반응이 없던 10개월 된 난치성 가와사끼병 환아에게 항 $TNF-{\alpha}$인 infliximab (5 mg/kg, 1회)을 투여하여 임상 호전과 더불어 항염증지표가 정상이 되고 관상동맥류 진행이 억제됨을 경험하였다.

• Journal of Ginseng Research
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• 제39권3호
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• pp.206-212
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• 2015

Background: Ginseng total saponin (GTS) contains various ginsenosides. These ginsenosides are widely used for treating cardiovascular diseases in Asian communities. The aim of this study was to study the effects of GTS on cardiac injury after global ischemia and reperfusion (I/R) in isolated guinea pig hearts. Methods: Animals were subjected to normothermic ischemia for 60 minutes, followed by 120 minutes of reperfusion. GTS significantly increased aortic flow, coronary flow, and cardiac output. Moreover, GTS significantly increased left ventricular systolic pressure and the maximal rate of contraction ($+dP/dt_{max}$) and relaxation ($-dP/dt_{max}$). In addition, GTS has been shown to ameliorate electrocardiographic changes such as the QRS complex, QT interval, and RR interval. Results: GTS significantly suppressed the biochemical parameters (i.e., lactate dehydrogenase, creatine kinase-MB fraction, and cardiac troponin I levels) and normalized the oxidative stress markers (i.e., malondialdehyde, glutathione, and nitrite). In addition, GTS also markedly inhibits the expression of interleukin-$1{\beta}$ (IL-$1{\beta}$), IL-6, and nuclear factor-${\kappa}B$, and improves the expression of IL-10 in cardiac tissue. Conclusion: These data indicate that GTS mitigates myocardial damage by modulating the biochemical and oxidative stress related to cardiac I/R injury.

• Journal of Microbiology and Biotechnology
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• 제30권3호
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• pp.333-340
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• 2020

Macrophages are the cells of the first-line defense system, which protect the body from foreign invaders such as bacteria. However, Gram-negative bacteria have always been the major challenge for macrophages due to the presence of lipopolysaccharides on their outer cell membrane. In the present study, we evaluated the effect of phloretin, a flavonoid commonly found in apple, on the protection of macrophages from Escherichia coli infection. RAW 264.7 cells infected with standard E. coli, or virulent E. coli K1 strain were treated with phloretin in a dose-dependent manner to examine its efficacy in protection of macrophages. Our results revealed that phloretin treatment reduced the production of nitric oxide (NO) and generation of reactive oxygen species along with reducing the secretion of proinflammatory cytokines induced by the E. coli and E. coli K1 strains in a concentration-dependent manner. Additionally, treatment of phloretin downregulated the expression of E. coli-induced major inflammatory markers i.e. cyclooxygenase-2 (COX-2) and hemeoxygenase-1 (HO-1), in a concentration dependent manner. Moreover, the TLR4-mediated NF-κB pathway was activated in E. coli-infected macrophages but was potentially downregulated by phloretin at the transcriptional and translational levels. Collectively, our data suggest that phloretin treatment protects macrophages from infection of virulent E. coli K1 strain by downregulating the TLR4-mediated signaling pathway and inhibiting NO and cytokine production, eventually protecting macrophages from E. coli-induced inflammation.

• Toxicological Research
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• 제32권2호
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• pp.133-140
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• 2016

Sulfasalzine is a widely administered drug against inflammatory-based disorders in human. However several cases of liver injury are associated with its administration. There is no stabilized safe protective agent against sulfasalazine-induced liver injury. Current investigation was designed to evaluate if N-acetylcysteine (NAC) and dithioteritol (DTT) as thiol reducing agents and/or vitamins C and E as antioxidants have any protective effects against sulfasalazine-induced hepatic injury in an ex vivo model of isolated rat liver. Rat liver was canulated and perfused via portal vein in a closed recirculating system. Different concentrations of sulfasalazine and/or thiol reductants and antioxidants were administered and markers of organ injury were monitored at different time intervals. It was found that 5 mM of sulfasalazine caused marked liver injury as judged by rise in liver perfusate level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) (p < 0.05). A significant amount of lipid peroxidation and hepatic glutathione depletion were detected in drug-treated livers, accompanied with significant histopathological changes of the organ. Administration of NAC ($500{\mu}M$), DTT (${400\mu}M$), Vitamin C ($200{\mu}M$), or vitamin E ($200{\mu}M$) significantly alleviated sulfasalazine-induced hepatic injury in isolated perfused rat liver. The data obtained from current investigation indicate potential therapeutic properties of thiol reductants and antioxidants against sulfasalazine-induced liver injury.

• 동의생리병리학회지
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• 제22권4호
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• pp.993-999
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• 2008

Ischemic brain injury such as cerebral infarction is characterized by acute local inflammatory response mediated by cytokines. The mechanism of cytokines involved in cerebral infarction progression are uncompletely revealed yet. We investigated to find out the relationship between single nucleotide polymorphism (SNP) of interleukin 4 receptor(IL4R) and Oriental Medicine therapy efficacy in patients with cerebral infarction for 2 weeks. Oriental Korean Medicine therapies (herbal medicine and acupuncture) were applied daily and motor functions of patients were assessed using the modified cerebral vascular accident (MCVA) scores. Genotyping for IL4R polymorphism was done by pyrosequencing analysis. In IL4R genotypes and the frequency of alleles, there was no significant difference between cerebral infarction patients (n=124) and controls group (n=175). And there was also no significant difference among good and bad responders in cerebral infarction patients. In this study the IL4R genotype might not be the risk factor or a good predictive genetic marker for good and bad responders in cerebral infarction patients in Korean. Further studies including different cytokine genes will be necessary for the exact genetic markers.

• Molecular & Cellular Toxicology
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• 제4권3호
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• pp.183-191
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• 2008

Volatile organic compounds (VOCs) are common constituents of cleaning and degreasing agents, paints, pesticides, personal care products, gasoline and solvents. And VOCs are evaporated at room temperature and most of them exhibit acute and chronic toxicity to human. Benzene is the most widely used prototypical VOC and the toxic mechanisms of them are still unclear. The multi-step process of toxic mechanism can be more fully understood by characterizing gene expression changes induced in cells by toxicants. In this study, DNA microarray was used to monitor the expression levels of genes in HepG2 cells and HL-60 cells exposed to the benzene on IC20 and IC50 dose respectively. In the clustering analysis of gene expression profiles, although clusters of HepG2 and HL-60 cells by benzene were divided differently, expression pattern of many genes observed similarly. We identified 916 up-regulated genes and 1,144 down-regulated genes in HepG2 cells and also 1,002 up-regulated genes and 919 down-regulated genes in HL-60 cells. The gene ontology analysis on genes expressed by benzene in HepG2 and HL-60 cells, respectively, was performed. Thus, we found some principal pathways, such as, focal adhesion, gap junction and signaling pathway in HepG2 cells and toll-like receptor signaling pathway, MAPK signaling pathway, p53 signaling pathway and neuroactive ligand-receptor interaction in HL-60 cells. And we also found 16 up-regulated and 14 down-regulated commonly expressed total 30 genes that belong in the same biological process like inflammatory response, cell cycle arrest, cell migration, transmission of nerve impulse and cell motility in two cell lines. In conclusion, we suggest that this study is meaningful because these genes regarded as strong potential biomarkers of benzene independent of cell type.

• Nutrition Research and Practice
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• 제8권5호
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• pp.544-549
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• 2014

BACKGROUND/OBJECTIVES: Obesity-associated insulin resistance is a strong risk factor for type 2 diabetes mellitus. The aim of this study was to investigate the effect of myricetin on adiposity, insulin resistance, and inflammatory markers in mice with diet-induced insulin resistance. MATERIALS/METHODS: Five-week-old male C57BL/6J mice were fed a basal diet, a high-fat, high-sucrose (HFHS) diet, or the HFHS diet containing 0.06% myricetin or 0.12% myricetin for 12 weeks after a 1-week adaptation, and body weight and food intake were monitored. After sacrifice, serum lipid profiles, glucose, insulin, adipocyte-derived hormones, and proinflammatory cytokines were measured. The homeostasis model assessment for insulin resistance (HOMA-IR) was determined. RESULTS: Myricetin given at 0.12% of the total diet significantly reduced body weight, weight gain, and epidydimal white adipose tissue weight, and improved hypertriglyceridemia and hypercholesterolemia without a significant influence on food intake in mice fed the HFHS diet. Serum glucose and insulin levels, as well as HOMA-IR values, decreased significantly by 0.12% myricetin supplementation in mice fed the HFHS diet. Myricetin given at 0.12% of the total diet significantly reduced serum levels of leptin, tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interleukin-6 (IL-6) in mice fed the HFHS diet. CONCLUSIONS: These findings suggest that myricetin may have a protective effect against diet-induced obesity and insulin resistance in mice fed HFHS diet, and that alleviation of insulin resistance could partly occur by improving obesity and reducing serum proinflammatory cytokine levels.