• The Korean Journal of Physiology and Pharmacology
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• v.22 no.2
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• pp.193-201
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• 2018

Connective tissue growth factor (CTGF) is a novel fibrotic mediator, which is considered to mediate fibrosis through extracellular matrix (ECM) synthesis in diabetic cardiovascular complications. Statins have significant immunomodulatory effects and reduce vascular injury. We therefore examined whether fluvastatin has anti-fibrotic effects in vascular smooth muscle cells (VSMCs) and elucidated its putative transduction signals. We show that advanced glycation end products (AGEs) stimulated CTGF mRNA and protein expression in a time-dependent manner. AGE-induced CTGF expression was mediated via ERK1/2, JNK, and Egr-1 pathways, but not p38; consequently, cell proliferation and migration and ECM accumulation were regulated by CTGF signaling pathway. AGE-stimulated VSMC proliferation, migration, and ECM accumulation were blocked by fluvastatin. However, the inhibitory effect of fluvastatin was restored by administration of CTGF recombinant protein. AGE-induced VSMC proliferation was dependent on cell cycle arrest, thereby increasing G1/G0 phase. Fluvastatin repressed cell cycle regulatory genes cyclin D1 and Cdk4 and augmented cyclin-dependent kinase inhibitors p27 and p21 in AGE-induced VSMCs. Taken together, fluvastatin suppressed AGE-induced VSMC proliferation, migration, and ECM accumulation by targeting CTGF signaling mechanism. These findings might be evidence for CTGF as a potential therapeutic target in diabetic vasculature complication.

• IMMUNE NETWORK
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• v.10 no.4
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• pp.126-134
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• 2010

Background: $CD8^+$ T cells contribute to the clearance of Hepatitis B virus (HBV) infection and an insufficient $CD8^+$ T cell response may be one of the major factors leading to chronic HBV infection. Since the HBx antigen of HBV can up-regulate cellular expression of several immunomodulatory molecules, we hypothesized that HBx expression in hepatocytes might affect $CD8^+$ T cell activity. Methods: We analyzed the activation and apoptosis of $CD8^+$ T cells co-cultured with primary hepatocytes rendered capable of expressing HBx by recombinant baculovirus infection. Results: Expression of HBx in hepatocytes induced low production of $interferon-{\gamma}$ and apoptosis of CD8+ T cells, with no effect on CD8 T cell proliferation. However, transcriptional levels of H-2K, ICAM-1 and PD-1 ligand did not correlate with HBx expression in hepatocytes. Conclusion: Our results suggest that HBx may inhibit $CD8^+$ T cell response by regulation of $interferon-{\gamma}$ production and apoptosis.

• Advances in Traditional Medicine
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• v.3 no.2
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• pp.72-79
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• 2003

The present investigation was undertaken to study whether tumor-associated macrophages of Daltons lymphoma (DL), a spontaneous transplantable T cell lymphoma can be activated to tumoricidal state by alcoholic extract of Tinospora cordifolia (ALTC). In vivo administration of ALTC (200 mg/kg body weight) in DL-bearing mice resulted in an enhanced RNI production and an augmented cytotoxic response of tumor-associated macrophages. Earlier we had reported that DL-bearing mice show a regression of thymus and an enlargement of spleen. In vivo administration of ALTC to DL-bearing hosts resulted in a decrease in the weight of spleen and counts of splenocytes along with an increase in the weight of thymus as compared to control DL-bearing mice. In vivo administration of ALTC in DL-bearing mice also resulted in an increase in the proliferation of splenocytes/thymocytes and BMC. The results of this study indicate that the ALTC upon in vivo administration in DL-bearing shows immuno-modulatory effects and thus may have clinical significance.

• Korean Journal of Pharmacognosy
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• v.25 no.4 s.99
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• pp.348-355
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• 1994

An antitumor component, F-D-P, was purified from the hot water extract of the carpophores of Elfvingia applanata by precipitation with ethanol, dialysis, and passage through a column of DEAE-cellulose ion exchange. F-D-P inhibited the growth of Sarcoma 180 in mice showing the tumor inhibition ratio of 88.3% in doses of 20 mg/kg for ten days. Chemical analysis of F-D-P showed that it was composed of polysaccharide(65.3%) and protein(6.5%0, and that the monosaccharides consisting of the polysaccharide was glucose(89.1%) and mannose(10.9%). The immunomodulatory activities of F-D-P were explored by determining its effect on the proliferation of the whole and subpopulations of lymphocytes, and on the generation of natural killer(NK) cell activity in vitro. F-D-P was mitogenic to total lymphocytes and B cells, but not to purified T cells, even in the presence of accessory cells. F-D-P did not increase NK cell activity when added to cultures of resting lymphocytes. From these results, it is clear that F-D-P modulates primarily the humoral immune responeses.

• The Journal of Korean Medicine
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• v.30 no.6
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• pp.69-79
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• 2009

Objective: In this study, the immunomodulatory activity of a mixture of wild Panax ginseng and red-mold rice extracts (MPR) on RAW 264.7 macrophage cells in the presence and absence of methotrexate (MTX), an anti-cancer drug, was investigated. Methods and Results: In the cell viability, MPR showed a significant cell proliferation and inhibited cell regression by red-mold rice (RMR) alone or MTX alone. MPR induced moderate increase in nitric oxide (NO) production. NO production and inducible nitric oxide synthase (iNOS) mRNA expression by LPS decreased after MPR treatment. In addition, MPR slightly induced COX-2 mRNA expression, but it did not affect the expression of COX-2 mRNA by LPS treatment. In RT-PCR analyses, MPR induced IL-$1{\alpha}$, IL-$1{\beta}$, IL-6, and TNF-$\alpha$ mRNA expression, but had no effect on IL-10 and TGF-$\beta$, regardless of MTX treatment. Furthermore, MPR did not interfere with the cytotoxicity of MTX against MCF-7 human breast carcinoma cells. Conclusions: MPR is efficacious in protecting against MTX-induced cell regression as a result of macrophage activation, resulting in induction of cytokine expression, implying that MPR could be considered an adjuvant in MTX-chemotherapy.

• Biomolecules & Therapeutics
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• v.22 no.1
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• pp.55-61
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• 2014

Panax ginseng is a medicinal herb that is used worldwide. Its medicinal effects are primarily attributable to ginsenosides located in the root, leaf, seed, and flower. The flower buds of Panax ginseng (FBPG) are rich in various bioactive ginsenosides, which exert immunomodulatory and anti-inflammatory activities. The aim of the present study was to assess the effect of 18 ginsenosides isolated from steamed FBPG on the transcriptional activity of NF-${\kappa}B$ and the expression of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$)-stimulated target genes in liver-derived cell lines. Noticeably, the ginsenosides $Rk_3$ and $Rs_4$ exerted the strongest activity, inhibiting NF-${\kappa}B$ in a dose-dependent manner. SF and $Rg_6$ also showed moderately inhibitory effects. Furthermore, these four compounds inhibited the TNF-${\alpha}$-induced expression of IL8, CXCL1, iNOS, and ICAM1 genes. Consequently, ginsenosides purified from steamed FBPG have therapeutic potential in TNF-${\alpha}$-mediated diseases such as chronic hepatic inflammation.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.5
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• pp.1323-1329
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• 2005

This study was carried out to know the immunity responses of Sogyughwalhyel-tanggami(SGHHT) to on Rheumatoid Arthritis in Collagen-induced Arthritis(CIA) Mice. Various experimental were peformed to analyse the immunity effects of SGHHT. The cytotoxicity against mLFCs was not measured. The production of pro-inflammatory cytokines $IL-1{\beta}$, IL-6, $TNF-\alpha$ were reduced in hFLSs. The production of pro-inflammatory cytokines $IFN-\gamma$, IgG3, IgG2b, IgM were reduced. Comparison of the results for this study showed that SGHHT had immunomodulatory effects of suppressing or enhancing. So we expect that SGHHT should be used as a effective drugs for not only rheumatoid arthritis but also another auto-immune disease. Therefore we have to survey continuously in looking for the effective substance and mechanism in the future.

• Biomolecules & Therapeutics
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• v.23 no.5
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• pp.414-420
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• 2015

Flavonoids, such as fisetin (3,7,3',4'-tetrahydroxyflavone), are plant secondary metabolites. It has been reported that fisetin is able to perform numerous pharmacological roles including anti-inflammatory, anti-microbial, and anti-cancer activities; however, the exact anti-inflammatory mechanism of fisetin is not understood. In this study, the pharmacological action modes of fisetin in lipopolysaccharide (LPS)-stimulated macrophage-like cells were elucidated by using immunoblotting analysis, kinase assays, and an overexpression strategy. Fisetin diminished the release of nitric oxide (NO) and reduced the mRNA levels of inducible NO synthase (iNOS), tumor necrosis factor (TNF)-${\alpha}$, and cyclooxygenase (COX)-2 in LPS-stimulated RAW264.7 cells without displaying cytotoxicity. This compound also blocked the nuclear translocation of p65/nuclear factor (NF)-${\kappa}B$. In agreement, the upstream phosphorylation events for NF-${\kappa}B$ activation, composed of Src, Syk, and I${\kappa}B{\alpha}$, were also reduced by fisetin. The phospho-Src level, triggered by overexpression of wild-type Src, was also inhibited by fisetin. Therefore, these results strongly suggest that fisetin can be considered a bioactive immunomodulatory compound with anti-inflammatory properties through suppression of Src and Syk activities.

• Korean Journal of Medicinal Crop Science
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• v.17 no.1
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• pp.8-14
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• 2009

Pueraria lobata (Willd.) Ohwi was investigated to check its modulatory effects on the activation of macrophages upon inflammatory conditions treatment. For this purpose, we examined several inflammatory responses such as nitric oxide (NO) production, reactive oxygen species (ROS) generation, cytoprotection and phagocytosis under the treatment of methanol extract from P. lobata (Pl-ME). Pl-ME dose-dependently blocked NO production in lipopolysaccharide (LPS)- stimulated RAW264.7 cells but not sodium prusside (SNP)-generated NO release. The NO inhibition seemed to be due to blocking inducible NO synthase (iNOS), since Pl-ME suppressed its expression in a NF-${\kappa}B$-independent manner. Similarly, this extract also effectively protected RAW264.7 cells from LPS-induced cytotoxicity. However, Pl-ME did not block ROS generation and rather it enhanced. Finally, this extract negatively modulated FITC-dextran uptake. Therefore, our data suggested that Pl-ME may be involved in negatively regulating some macrophage-mediated inflammatory responses such as NO production and phagocytic uptake.

• Journal of Ginseng Research
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• v.44 no.4
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• pp.538-543
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• 2020

Cardiovascular diseases are a rapidly growing epidemic with high morbidity and mortality. There is an urgent need to develop nutraceutical-based therapy with minimum side effects to reduce cardiovascular risk. Panax ginseng occupies a prominent status in herbal medicine for its various therapeutic effects against inflammation, allergy, diabetes, cardiovascular diseases, and even cancer, with positive, beneficial, and restorative effects. The active components found in most P. ginseng varieties are known to include ginsenosides, polysaccharides, peptides, alkaloids, polyacetylene, and phenolic compounds, which are considered to be the main pharmacologically active constituents in ginseng. P. ginseng is an adaptogen. That is, it supports living organisms to maintain optimal homeostasis by exerting effects that counteract physiological changes caused by physical, chemical, or biological stressors. P. ginseng possesses immunomodulatory (including both immunostimulatory and immunosuppressive), neuromodulatory, and cardioprotective effects; suppresses anxiety; and balances vascular tone. P. ginseng has an antihypertensive effect that has been explained by its vasorelaxant action, and paradoxically, it is also known to increase blood pressure by vasoconstriction and help maintain cardiovascular health. Here, we discuss the potential adaptogenic effects of P. ginseng on the cardiovascular system and outline a future research perspective in this area.