• The Korean Journal of Physiology and Pharmacology
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• 제25권1호
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• pp.27-38
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• 2021

Excessive salt intake induces hypertension, but several gamma-aminobutyric acid (GABA) supplements have been shown to reduce blood pressure. GABA-salt, a fermented salt by L. brevis BJ20 containing GABA was prepared through the post-fermentation with refined salt and the fermented GABA extract. We evaluated the effect of GABA-salt on hypertension in a high salt, high cholesterol diet induced mouse model. We analyzed type 1 macrophage (M1) polarization, the expression of M1 related cytokines, GABA receptor expression, endothelial cell (EC) dysfunction, vascular smooth muscle cell (VSMC) proliferation, and medial thicknesses in mice model. GABA-salt attenuated diet-induced blood pressure increases, M1 polarization, and TNF-α and inducible nitric oxide synthase (NOS) levels in mouse aortas, and in salt treated macrophages in vitro. Furthermore, GABA-salt induced higher GABAB receptor and endothelial NOS (eNOS) and eNOS phosphorylation levels than those observed in salt treated ECs. In addition, GABA-salt attenuated EC dysfunction by decreasing the levels of adhesion molecules (E-selectin, Intercellular Adhesion Molecule-1 [ICAM-1], vascular cell adhesion molecule-1 [VCAM-1]) and of von Willebrand Factor and reduced EC death. GABA-salt also reduced diet-induced reductions in the levels of eNOS, phosphorylated eNOS, VSMC proliferation and medial thickening in mouse aortic tissues, and attenuated Endothelin-1 levels in salt treated VSMCs. In summary, GABA-salt reduced high salt, high cholesterol diet induced hypertension in our mouse model by reducing M1 polarization, EC dysfunction, and VSMC proliferation.

• Korean Journal of Acupuncture
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• 제27권1호
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• pp.31-47
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• 2010

Objectives: To investigate the anti-inflammatory effects of cultivated wild ginseng pharmacopuncture in lipopolysaccharide (LPS)-induced inflammatory rat model. Methods: Sprague-Dawley rats were divided into 4 groups; LPS control (n=6), LPS+cultivated wild ginseng pharmacopuncture at CV4 (n=6), LPS+cultivated wild ginseng pharmacopuncture at CV17 (n=6), and LPS+cultivated wild ginseng pharmacopuncture at Ex-HN1 (n=6). Pharmacopuncture (0.1 ml) was given every two days for 4 weeks followed by inflammation induction by peritoneal LPS injection (5 mg/kg). Blood, liver tissue, and peritoneal lavage fluid were taken and proinflammatory cytokines and other related factors were analysed. Results: Compared with the control group, CV4 and Ex-HN1 pharmacopuncture groups significantly attenuated plasma IL-$1{\beta}$, IL-6, and TNF-$\alpha$ increase at 2h and 5h after LPS injection (P<0.05). A significant difference from control group emerged at 5 h for plasma IL10 (P<0.05). For liver cytokines analyzed at 5 h after LPS injection, only CV4 pharmacopuncture group showed significant difference in TNF-$\alpha$ and IL-10 (P<0.05). Blood 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). CV4 pharmacopuncture significantly attenuated increase of plasma ${NO_3}^-/{NO_2}^-$, Intracellular adhesion molecule-1 (ICAM-1), cytokine-induced neutrophil chemoattractant-1 (CINC-1), and prostaglandin $E_2$ ($PGE_2$) compared with the control group (P<0.05). Monocyte chemoattractant protein-1, $PGE_2$, and CINC-1 level of CV4 pharmacopuncture group was significantly different from those from the control group (P<0.05). Conclusions: These results indicate that cultivated wild ginseng pharmacopuncture at CV4 may have a potent anti-inflammatory effect in an LPS-induced inflammatory rat model.

• 대한한의학방제학회지
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• 제20권1호
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• pp.1-11
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• 2012

Objectives : This experimental study was designed to investigate the inhibitory effects of combination with Korean red ginseng and Gastrodia rhizoma on vascular dysfunction in high-fat/cholesterol diet-induced hyperlipidemia. Methods : Sprague-Dawley rats were fed with 7.5% cocoa butter and 1.25% cholesterol for 10 weeks, with Panax ginseng (PG), and mixtures of Panax ginseng and Gastrodia rhizoma (PGM), respectively. Results : Chronic treatment with PG and PGM significantly decreased body weight. The aortic expression of cell adhesion molecules such as intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin were markedly increased in hyperlipidemia rats. Interestingly, PGM significantly decreased cell adhesion molecules expression. However, there was no significant decrease in PG group. In addition, PG and PGM group inhibited high-fat/cholesterol diet-induced cytokine such as monocyte chemoattractant protein (MCP-1) mRNA expression. Furthermore, PG and PGM group significantly decreased c-reactive protein protein (CRP) level. Especially, PGM significantly accentuated the decrease of MCP-1 mRNA expression and CRP level. Conclusions : the present study provides an evidence that combination with Panax ginseng and Gastrodia rhizoma enhances anti-vascular protective effects through suppression of vascular inflammation in hyperlipidemic rats.

• BMB Reports
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• 제50권1호
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• pp.25-30
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• 2017

In the central nervous system, viral infection can induce inflammation by up-regulating pro-inflammatory mediators that contribute to enhanced infiltration of immune cells into the central nervous areas. Celastrol is known to exert various regulatory functions, including anti-microbial activities. In this study, we investigated the regulatory effects and the mechanisms of action of celastrol against astrocytes activated with polyinosinic-polycytidylic acid (poly(I:C)), a synthetic dsRNA, as a model of pro-inflammatory mediated responses. Celastrol significantly inhibited poly(I:C)-induced expression of adhesion molecules, such as ICAM-1/VCAM-1, and chemokines, such as CCL2, CXCL8, and CXCL10, in CRT-MG human astroglioma cells. In addition, celastrol significantly suppressed poly(I:C)-induced activation of JNK MAPK and STAT1 signaling pathways. Furthermore, celastrol significantly suppressed poly(I:C)-induced activation of the $NF-{\kappa}B$ signaling pathway. These results suggest that celastrol may exert its regulatory activity by inhibiting poly(I:C)-induced expression of pro-inflammatory mediators by suppressing activation of JNK MAPK-STAT1/$NF-{\kappa}B$ in astrocytes.

• 한국해양바이오학회지
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• 제1권3호
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• pp.156-162
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• 2006

The halophilic enterobacteria, Enterobacteria cancerogenus, was isolated from the intestines of the fusiform fish (Trachurus japonicus) to yield a protein-like material termed PLM-f74. PLM-f74 was characterized by strong inhibition ratios to angiogenesis (82.8% at the concentration of $18.5{\mu}g/mL$) and elevated antioxidative capacities with low toxicity. The PLM-f74 is a glycoprotein comprised of saccharides and amino acids. PLM-f74 inhibited non-activated U937 monocytic cell adhesion to HUVECs activated with IL-$1{\beta}$ by 78.0%, and the adherence of U937 cells treated with the PLM-f74 and stimulated with IL-$1{\beta}$ to unstimulated HUVECs decreased by 102%. When both cell types were pretreated with PLM-f74, the adhesion of U937 cells to IL-$1{\beta}$ stimulated HUVECs was completely suppressed by 121% at a concentration of 18.5 ug/mL. PLM-f74 blocked signal pathways from VEGFR2, PI3K, ${\beta}$-catenin and VE-cadherin to NF-kB based on western bolt analysis. And also inhibited IL-1-stimulated HUVEC expression of the adhesion molecules, ICAM-1 by 40%, VCAM-1 by 60%, and E-selectin by 70% at the same concentration noted above. New anti-angiogenic and anti-cell adhesion materials showing elevated antioxidative capacities and non-toxicity may be expected from these results.

• BMB Reports
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• 제52권10호
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• pp.613-618
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• 2019

Microglial cells are known as the main immune cells in the central nervous system, both regulating its immune response and maintaining its homeostasis. Furthermore, the antioxidant ${\alpha}-lipoic$ acid (LA) is a recognized therapeutic drug for diabetes because it can easily invade the blood-brain barrier. This study investigated the effect of ${\alpha}-LA$ on the inflammatory response in lipopolysaccharide (LPS)-treated BV-2 microglial cells. Our results revealed that ${\alpha}-LA$ significantly attenuated several inflammatory responses in BV-2 microglial cells, including pro-inflammatory cytokines, such as tumor necrosis $factor-{\alpha}$ and interleukin (IL)-6, and other cytotoxic molecules, such as nitric oxide and reactive oxygen species. In addition, ${\alpha}-LA$ inhibited the LPS-induced phosphorylation of ERK and p38 and its pharmacological properties were facilitated via the inhibition of the nuclear factor kappa B signaling pathway. Moreover, ${\alpha}-LA$ suppressed the activation of NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasomes, multiprotein complexes consisting of NLRP3 and caspase-1, which are involved in the innate immune response. Finally, ${\alpha}-LA$ decreased the genes accountable for the M1 phenotype, $IL-1{\beta}$ and ICAM1, whereas it increased the genes responsible for the M2 phenotype, MRC1 and ARG1. These findings suggest that ${\alpha}-LA$ alleviates the neuroinflammatory response by regulating microglial polarization.

• 대한한방부인과학회지
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• 제34권4호
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• pp.1-11
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• 2021

Objectives: Nephrotic syndrome is a kidney disorder, which is characterized by proteinuria, edema (swelling), and hyperlipidemia. Maydis Stigma (Corn silk) has been widely used in Asia as a traditional medicine and is known to have a diuretic effect and is used for the treatment of edema and indigestion. Methods: The aim of this study is to investigate the improvement effect of Maydis Stigma in treating nephrotic syndrome induced by puromycin aminonucleoside. Sprague-Dawley rats were intravenously injected with 75 mg/kg/day puromycin aminonucleoside, then treated with either Losartan or 200 mg/kg/day Maydis Stigma for seven days. Results: Maydis Stigma significantly decreased ascites and proteinuria level. Plasma levels of blood urea nitrogen (BUN) and plasma creatinine reduced significantly by Maydis Stigma. In addition, treatment with Maydis Stigma attenuated histological damage. Treatment with Maydis Stigma also restored podocin expression and reduced inflammation markers such as intracellular adhesion molecules (ICAM-1), monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor alpha (TNF-α) and high-mobility group box-1 (HMGB1). Conclusions: Maydis Stigma ameliorates kidney injury in nephrotic syndrome rat models. Maydis Stigma exerts a renoprotective effect owing to its anti-inflammatory effects and reductions of ascites and proteinuria. Thus, these results indicate that Maydis Stigma is likely to be a promising agent in the treatment of nephrotic syndrome.

• 대한한의학방제학회지
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• 제22권1호
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• pp.93-104
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• 2014

Objectives : Samhwangsasim-tang (SHSST) is a traditional Korean medication, which has been used in Korea for treatment of hypertension and chest pain. Hyperlipidemia and inflammation could influence hypertension and chest pain. This study investigated whether and how SHSST reduces the hyperlipidemia and inflammation related to high-cholesterol diet-induced obesity in rats. Methods : Mice were divided randomly into four groups: the normal diet group, high-cholesterol diet group, low dose treatment group supplemented with 30% ethanol extract of SHSST (L) and high dose treatment group supplemented with 80% ethanol extract of SHSST (H). L and H groups were orally administered with SHSST at the dose of 50mg/kg a day respectively and others were administered with the same volume of physiological saline. Results : Administration of SHSST resulted in a decrease in serum levels of total cholesterol and low-density lipoprotein. Expression of hepatic genes(SREBP2, LXR, LDLR, and HMG-CoA) related with cholesterol metabolism was also suppressed. In addition, SHSST decreased the expression of inflammation-related gene (TNF-${\alpha}$, IL-6, ICAM-1, VCAM-1, TGF-${\beta}1$ and fibronectin). Histological examinations also showed that the size of the adipocytes was smaller in the SHSST treated group than in the high-colesterol diet group. In an in vitro study, SHSST inhibited the production of nitric oxide in a concentration-dependent manner. Conclusions : This study indicates that SHSST has anti-hyperlipidemia and anti-inflammatory effects. It may also suggest that SHSST may be alternative therapy for treatment of hyperlipidemia and its complications.

• 대한한의학방제학회지
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• 제21권1호
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• pp.119-130
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• 2013

Objectives : Diabetes mellitus is the leading cause for vascular complications such as atherosclerosis. The present study is to investigate whether Doinseunggi-tang (DST) improves diabetic vascular dysfunction in type II diabetes. Methods : The db/db mice were treated with high fat/high cholesterol diet and DST (200 mg/kg/day) for 8 weeks. Results : DST significantly lowered blood glucose and systolic blood pressure. In addition, DST also markedly decreased total plasma cholesterol, triglyceride, and LDL-cholesterol, whereas increased the HDL-cholesterol. Vascular relaxation of aortic rings by acetylcholine or SNP was ameliorated by DST in a dose-dependent manner. Damage of vascular intima and hypertrophic of media was improved by DST. Immunohistological study revealed that DST attenuated the increase of ICAM-1, VCAM-1, and ET-1 expression in thoracic aorta. Conclusions : Taken together, DST suppressed hyperglycemia and diabetic vascular dysfunction in type II db/db mice. The present data suggests that Doinseunggi-tang may be prevent a development of diabetic atherosclerosis.

• IMMUNE NETWORK
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• 제7권2호
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• pp.57-65
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• 2007

Background: Cordyceps militaris have been reported to modify the immune and inflammatory responses both in vivo and in vitro. Macrophages play important roles in the innate immunity through the phagocytosis of antigens. This study examined the effects of Cordyceps militaris on the activation of murine macrophage RAW 264.7 cells and primary macrophages. Methods: The components contained in culture broth of Cordyceps militaris were purified by propyl alcohol extraction and HP 20 column chromatography to CMDB, CMDBW, CMDB5P, and CMDB25P. The amounts of nitric oxide (NO) were determined by using ELISA, Griess reagent respectively. The amounts of some cytokines were determined by using ELISA, western blot, and RT-PCR The expression levels of cell surface molecules (ICAM-1, B7-1 and B7-2) were measured by flow cytometric analysis. Results: All the components of Cordyceps militaris produced significant amounts of NO. In particular, CMDB produced much more NO in RAW 264.7 cells and primary macrophages than other fractions of Cordyceps militaris. CMDB increased significantly the production of tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-1${\beta}$, and IL-6 dose-dependently in RAW 264.7 cells. Examination of the gene expression level also showed that the enhanced production of cytokines was correlated with the up-regulation of i-NOS expression, cycloxygenase (COX)-2 expression, IL-1${\beta}$ and IL-6 expression, and TNF-${\alpha}$ expression on the expression of mRNAs by semi-quantitative RT-PCR Western blot analysis also confirmed that CMDB enhances the expression level of these cytokines. Conclusion: These results show that CMDB stimulates the production of NO and pro-inflammatory cytokines and can also up-regulate the gene expression levels in macrophages.