• Journal of Ginseng Research
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• v.44 no.6
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• pp.833-842
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• 2020

Background: Ulcerative colitis (UC) is a commonly encountered large intestine disease in the contemporary world that terminates into colorectal cancer; therefore, the timely treatment of UC is of major concern. Panax ginseng Meyer is an extensively consumed herbal commodity in South East Asian countries, especially Korea. It exhibits a wide range of biologically beneficial qualities for almost head-to-toe ailments in the body. Epimedium koreanum Nakai (EKN) is also a widely used traditional Korean herbal medicine used for treating infertility, rheumatism, and cardiovascular diseases. Materials and methods: Separately the anti-inflammatory activities of both red ginseng extracts (RGEs) and EKNs had been demonstrated in the past in various inflammatory models; however, we sought to unravel the anti-inflammatory activities of the combination of these two extracts in dextran sulfate sodium (DSS)-induced ulcerative colitis in mice model because the allopathic remedies for UC involve more side effects than benefits. Results: Our results have shown that the combination of RGE + EKN synergistically alleviated the macroscopic lesions in DSS-induced colitic mice such as colon shortening, hematochezia, and weight loss. Moreover, it restored the histopathological lesions in mice and decreased the levels of proinflammatory mediators and cytokines through the repression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP-3) expression. In vitro, this combination also reduced the magnitude of nitric acid (NO), proinflammatory mediators and cytokine through NF-κB and mitogen-activated protein kinase (MAPK) pathways in RAW 264.7 mouse macrophage cells. Conclusion: In the light of these findings, we can endorse this combination extract as a functional food for the prophylactic as well as therapeutic treatment of UC in humans together with allopathic remedies.

• IMMUNE NETWORK
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• v.3 no.4
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• pp.310-319
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• 2003

Inflammatory mediators has been recognized as an important role in the pathogenesis of rheumatoid arthritis (RA). IL-17 is increasingly recognized as an important regulator of immune and inflammatory responses, including induction of proinflammatory cytokines and osteoclastic bone resorption. Evidence of the expression and proinflammatory activity of IL-17 has been demonstrated in RA synovium and in animal models of RA. However, the signaling pathways that regulate IL-17 production remain unknown. In the present study, we investigated the role of the phosphatidylinositol 3 kinase (PI3K)-Akt pathway in the regulation of IL-17 production in RA. PBMC were separated from RA (n=24) patients, and stimulated with various agents (anti CD3, anti CD28, PHA, ConA, IL-15). IL-17 levels were determined by sandwich ELISA and RT-PCR. The production of IL-17 was significantly increased in cells treated with anti-CD3 antibody, PHA, IL-15 or MCP-1 (P<0.05). ConA also strongly induced IL-17 production (P<0.001), whereas TNF-alpha, IL-1beta, IL-18 or TGF-beta did not. IL-17 was detected in the PBMC of patients with osteoarthritis (OA) but their expression levels were much lower than those of RA PBMC. Anti-CD3 antibody activated the PI3K-Akt pathway and activation of the PI3K-Akt pathway resulted in a pronounced augmentation of nuclear factor kappaB ($NF-{\kappa}B$). IL-17 production by activated PBMC in RA is completely or partially blocked in the presence of $NF-{\kappa}B$ inhibitor PDTC and PI3K-Akt inhibitor, wortmannin and LY294002, respectively. Whereas the inhibition of AP-1 and extracellular signal-regulated kinase (ERK)1/2 did not affect IL-17 production. These results provide new insight into that PI3K/Akt and $NF-{\kappa}B$ dependent signal transduction pathway could be involved in the overproduction of key inflammatory cytokine, IL-17 in rheumatoid arthritis.

• Journal of Life Science
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• v.18 no.11
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• pp.1551-1560
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• 2008

Cytokines play a pivotal role in systemic inflammatory response following cardiac surgery with cardiopulmonary bypass (CPB). The purpose of this study was to investigate the perioperative changes in proinflammatory [tumor necrosis factor-$\alpha$ (TNF-$\alpha$) and interleukin-6 (IL-6)] and antiinflammatory cytokines [interleukin-10 (IL-10)], and each correlation between the cytokines and other variables in valvular heart surgery with CPB. Serum IL-6 and IL-10 levels and leukocyte counts significantly increased following CPB. CPB caused hepatic, renal and myocardial dysfunctions. IL-6 levels had positive correlations with IL-10 levels at postoperative periods. TNF-$\alpha$ levels had correlations with leukocyte counts and myocardial marker levels at postoperative 24 hr (PO-24 h). Furthermore, IL-6 or IL-10 levels had positive correlations with other variable such as hepatic, renal or myocardial marker at postoperative periods. These results showed that balance between proinflammatory and antiinflammatory cytokines is maintained during cardiac surgery with CPB, and that these cytokines exert postoperatively inflammatory and antiinflammatory reactions.

• The Journal of Internal Korean Medicine
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• v.29 no.3
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• pp.543-553
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• 2008

Objective: The goal of this study was to determine the anti-asthma mechanism of SF on TNF-${\alpha}$ induced activation on A549 (human type II-like epithelial) cells. Using oligonucleotide microarray, we sought to establish the molecular mechanism of the protective effects of SF on A549 cells. Material & Methods : Cells were cultured in three different conditions: 1) negative control group was cultured in normal condition of DMEM, 2) positive control group was activated with TNF-${\alpha}$, IL-4. and IL-1${\beta}$, and 3) SF treated group was previously treated with 0.1${\mu}g/ml$ SF after TNF-${\alpha}$, IL-4. and IL-1 activation. Cells of positive control and SF treated groups were cultured for 30 min, 1hr, 3hr and 6hr. Results : The comparative analysis of the gene expression profile revealed that proinflammatory cytokines such as IL1F8, IL1F9, IL1R1. IL1RN, IL1RAPL1, IL8, TNFRSF4, TNFSF10c, TNFSF13, TRAF5, and TRAF7 and inflammation-related genes including MMP2, MMP11, MMP14, MMP15, MMP16, MMP19, MMP25, and MMP27 were down regulated with SF treatment. Cell adhesion molecule genes such as ITGB1, ITGBL1, selectin P ligand, selectin E, ICAM2, ICAM3, VCAM1, PECAM, FCER1G and MMP28 genes were also down-regulated in SF treated A549 cells. Conclusion : These results suggest that the anti-asthmatic effects of SF could be mediated by regulating specific genes related with cell adhesion, proinflammatory cytokine and inflammation-related genes in A549 cells.

• Korean Journal of Acupuncture
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• v.26 no.3
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• pp.55-68
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• 2009

Objectives : To investigate the anti-inflammatory effects of Scutellaria baicalensis Georgi pharmacopuncture in lipopolysaccharide (LPS)-induced inflammatory rat model. Methods : Sprague-Dawley rats were divided into 4 groups; LPS control (n=6), LPS+Scutellaria baicalensis Georgi pharmacopuncture at BL23 (n=6, BL23), LPS+Scutellaria baicalensis Georgi pharmacopuncture at CV12 (n=6, CV12), and LPS+Scutellaria baicalensis Georgi pharmacopuncture at GV4 (n=6, GV4). Pharmacopuncture was given every two days for 4 weeks followed by inflammation induction by intraperitoneal LPS injection (5mg/kg). Blood, liver tissue, and peritoneal lavage fluid were taken and proinflammatory cytokines and other related factors were analysed. Results : For proinflammatory cytokines, CV12 pharmacopuncture group was significantly different compared with the control group in plasma IL-$1{\beta}$, IL-6, TNF-$\alpha$, and IL-10 5 h after LPS injection (P<0.05). For plasma IL-$1{\beta}$ and IL-6, CV12 pharmacopuncture group also showed significant difference at 2 h compared with the control (P<0.05). GV4 pharmacopuncture group was significantly different compared with the control at 5 h in plasma IL-$1{\beta}$, IL-6, and TNF-$\alpha$ and at 2 h in IL-10 (P<0.05). Liver cytokines were analyzed at 5 h after LPS injection; only CV12 pharmacopuncture group showed significant difference in IL-$1{\beta}$ (P<0.05) and others including IL-6, TNF-$\alpha$, and IL-10 had no difference compared with the control group. CD4/CD8 ratio and the phagocytic activities of polymorphonuclear neutrophils were not different from those of control group in all pharmacopuncture groups (P>0.05). Plasma NO3-/NO2- and intracellular adhesion molecule-1 of CV12 pharmacopuncture group were significantly lower than that of the control group (P<0.05). In the plasma concentration of prostaglandin E2, all 3 pharmacopuncture groups had significantly lower values than that of the control group (P<0.05), but there was no difference among pharmacopucnture groups. Monocyte chemoattractant protein-1 and cytokine-induced neutorphil chemoattractant-1 in peritoneal lavage fluid was significantly decreased in CV12 pharmacopuncture group compared with the control group (P<0.05). Conclusions : These results indicate that Scutellaria baicalensis Georgi pharmacopuncture at CV12 may have a potent anti-inflammatory effect in an LPS-induced inflammatory rat model.

• Journal of Ginseng Research
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• v.40 no.3
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• pp.203-210
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• 2016

Background: Korean Red Ginseng (KRG) is a well-known natural product with anticarcinogenic and antioxidant effects. We evaluated the antifatigue effect of KRG in patients with nonalcoholic fatty liver disease (NAFLD). Methods: Eighty patients with NAFLD were prospectively randomized to receive 3 wk of KRG or placebo in addition to counseling on healthy eating and regular exercise. Liver function test, proinflammatory cytokines, adiponectin, antioxidant activity, and fatigue score were measured and compared according to the body mass index between the KRG and placebo groups. Results: The liver function tests were significantly improved after 3 wk of treatment in both groups. The mean levels (at baseline and after treatment) of tumor necrosis factor-${\alpha}$ were $108.0pg/mL{\pm}54.8pg/mL$ and $92.7pg/mL{\pm}39.0pg/mL$ (p = 0.018) in the KRG group and $123.1pg/mL{\pm}42.1pg/mL$ and $127.5pg/mL{\pm}62.2pg/mL$ (p = 0.694) in the placebo group, respectively. There was a significant difference in change of adiponectin levels between the KRG ($7,751.2pg/mL{\pm}3,108.1pg/mL$ and $8,197.3pg/mL{\pm}2,714.5pg/mL$) and placebo groups ($7,711.6pg/mL{\pm}3,041.3pg/mL$ and $7,286.1pg/mL{\pm}5,188.7pg/mL$, p = 0.027). In patients with overweight, the fatigue score was significantly decreased in the KRG group ($35.0{\pm}13.2$ and $24.5{\pm}8.9$, p = 0.019). Conclusion: Our results show that KRG might be effective in reducing proinflammatory cytokine and fatigue in overweight patients with NAFLD, in addition to improvements in adiponectin levels.

• IMMUNE NETWORK
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• v.8 no.1
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• pp.29-37
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• 2008

Interleukin-23 (IL-23) is a novel pro-inflammatory cytokine which has been implicated to play a pathogenic role in rheumatoid arthritis (RA). This study was undertaken to investigate the IL-23 inductive activity of the proinflammatory cytokine IL-17, $IL-1{\beta}$ and tumor necrosis factor (TNF-${\alpha}$) in RA synovial fluid mononuclear cells (SFMC). Expression of IL-23p19, IL-17, $IL-1{\beta}$ and TNF-${\alpha}$ in joint was examined by immunohistochemistry (IHC) of patients with RA and osteoarthritis (OA). The effects of IL-17 and $IL-1{\beta}$ on expression of IL-23p19 in human SFMC from RA patients were determined by reverse transcriptase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). IL-23p19 was expressed in the RA fibroblast like synoviocyte (FLS), but not from OA FLS. Similar to the protein expression, IL-23p19 mRNA could be detected by RT-PCR in RA SFMC. IL-17 and $IL-1{\beta}$ could induce RA SFMC to produce the IL-23p19. The effects of IL-17 were much stronger than $IL-1{\beta}$ or TNF-${\alpha}$. These responses were observed in a doseresponsive manner. In addition, IL-17 or $IL-1{\beta}$ neutralizing antibody down-regulated the expression of IL-23p19 induced by LPS in RA-SFMC. Our results demonstrate that IL-23p19 is overexpressed in RA synovium and IL-17 and $IL-1{\beta}$ appears to upregulate the expression of IL-23p19 in RA-SFMC.

• Journal of Nutrition and Health
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• v.51 no.5
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• pp.369-378
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• 2018

Purpose: Obesity is associated with a dysregulation of metabolic balance and is regarded as a low grade chronic inflammation. Western-style diet and physical inactivity are leading causes of obesity. This study examined the profiles of forty plasma cytokines and chemokines at the same time in the early stages of high-fat diet-induced obesity using a mouse model. Methods: A total of 30 male CD1 mice, 12 ~ 14 weeks of age, were enrolled. The mice were fed a high-fat diet for 6 weeks to induce obesity. The plasma glucose and triglyceride concentrations were measured using a hexokinase colorimetric assay kit and a serum triglyceride determination kit, respectively. The relative levels of multiple cytokines and chemokines in the plasma were determined using a mouse cytokine array kit. Results: The mice exhibited significant weight gain after 6 weeks of a high-fat diet. The genital fat depot was enlarged along with an increase in the number and the mean size of white adipocytes as early as 4 weeks after a high-fat diet. In addition, the plasma glucose and triglyceride levels increased significantly after 4 weeks of a high-fat diet. Cytokine array analysis revealed a remarkable increase in the expression of both CXCL12 and CXCL13, whereas the proinflammatory cytokines remained low after 4 weeks of a high-fat diet. Conclusion: A significant increase in plasma levels of CXCL12 and CXCL13 was observed after 4 weeks of a high-fat diet, which might induce the migration of B lymphocytes, T lymphocytes, and monocytes from the blood to expanding adipose tissue or fat associated lymphoid clusters, playing a key role in adipose tissue remodeling and local immunity during the early stages of high-fat diet-induced obesity.

• Journal of Nutrition and Health
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• v.53 no.2
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• pp.99-110
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• 2020

Purpose: The rice germ fraction is a better source of protein, lipid, and fiber than the rice endosperm. Furthermore, the rice germ is rich in bioactive phytochemicals such as γ-aminobutyric acid, tocopherols, tocotrienols, phytic acid, and so on. In this study, the phytosterol content and antioxidant activity of Keunnunjami germ (KG) or normal rice germ supplement were investigated in healthy adult rats. Methods: In vitro, quantitative assessment of phytosterols, including β-sitosterol, campesterol, cycloartenol, and stigmasterol, was performed. Comparative antioxidant activities of 2 rice germs were measured based on DPPH radical scavenging activity, reducing power, and ABTS radical scavenging capacity. In vivo, male Spraque-Dawley rats (30-weeks-old) were randomly assigned a diet of normal control (NC, AIN-93M diet), AIN-93M diet supplemented with normal rice germ 3% (NG3), or AIN-93M diet supplemented with KG 3% (KG3) and fed for 8 weeks. Results: KG contained significantly higher campesterol and stigmasterol contents and antioxidant activity than normal rice germ. The KG3 group exhibited significantly lower body weight gain as well as inguinal and total white adipose tissue weights. There were no significant differences in plasma glucose, insulin, C-peptide, or homeostasis model assessment of insulin resistance level among the 3 groups. The plasma tumor necrosis factor-α concentration was significantly lower while leptin, advanced oxidation protein products, and interleukin-6 showed downward trends in the KG3 group. In addition, the superoxide dismutase level of the KG3 group was significantly higher compared to the NC and NG3 groups. Conclusion: This study indicates that KG can be considered as a valuable source of phytosterol components. Lastly, KG has strong antioxidant properties and may have potential to ameliorate elevation of proinflammatory cytokine production with age.

• Clinical and Experimental Pediatrics
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• v.56 no.4
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• pp.151-158
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• 2013

Purpose: We investigated the mRNA levels of peroxisome proliferator-activated receptor (PPAR)-${\alpha}$, PPAR-${\gamma}$, adipokines, and cytokines in the lung tissue of lean and obese mice with and without ovalbumin (OVA) challenge, and the effect of rosiglitazone, a PPAR-${\gamma}$ agonist. Methods: We developed 6 mice models: OVA-challenged lean mice with and without rosiglitazone; obese mice with and without rosiglitazone; and OVA-challenged obese mice with and without rosiglitazone. We performed real-time polymerase chain reaction for leptin, leptin receptor, adiponectin, vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-${\alpha}$, transforming growth factor (TGF)-${\beta}$, PPAR-${\alpha}$ and PPAR-${\gamma}$ from the lung tissue and determined the cell counts and cytokine levels in the bronchoalveolar lavage fluid. Results: Mice with OVA challenge showed airway hyperresponsiveness. The lung mRNA levels of PPAR${\alpha}$ and PPAR-${\gamma}$ increased significantly in obese mice with OVA challenge compared to that in other types of mice and decreased after rosiglitazone administeration. Leptin and leptin receptor expression increased in obese mice with and without OVA challenge and decreased following rosiglitazone treatment. Adiponectin mRNA level increased in lean mice with OVA challenge. Lung VEGF, TNF-${\alpha}$, and TGF-${\beta}$ mRNA levels increased in obese mice with and without OVA challenge compared to that in the control mice. However, rosiglitazone reduced only TGF-${\beta}$ expression in obese mice, and even augmented VEGF expression in all types of mice. Rosiglitazone treatment did not reduce airway responsiveness, but increased neutrophils and macrophages in the bronchoalveolar lavage fluid. Conclusion: PPAR-${\alpha}$ and PPAR-${\gamma}$ expressions were upregulated in the lung tissue of OVA-challenged obese mice however, rosiglitazone treatment did not downregulate airway inflammation in these mice.