• Journal of Microbiology and Biotechnology
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• v.17 no.8
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• pp.1338-1343
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• 2007

Angiogenesis is an essential step in tumor progress and metastasis. Accordingly, small molecules that inhibit angiogenesis would appear to be a promising way to cure angiogenesis-related diseases, including cancer. In the present study, we report that streptochlorin, a small molecule from marine actinomycete, exhibits a potent antiangiogenic activity. The compound potently inhibited endothelial cell invasion and tube formation stimulated with vascular endothelial cell growth factor (VEGF) at low micromolar concentrations where it showed no cytotoxicity to the cells. In addition, streptochlorin inhibited TNF-${\alpha}$-induced $NF-{\kappa}B$ activation in the newly developed cell-based reporter gene assay. These data demonstrate that streptochlorin is a new inhibitor of $NF-{\kappa}B$ activation and can be a basis for the development of novel anti-angiogenic agents.

• Natural Product Sciences
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• v.15 no.3
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• pp.139-143
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• 2009

The anaphylactic allergic reaction is involved in many allergic diseases such as asthma and allergic rhinitis. In this report, I investigated the effect of ripe fruits of Rubus coreanus Miq. (Rosaceae) (RFRC) on the anaphylactic allergic reaction and studied its possible mechanisms of action. RFRC inhibited compound 48/80-induced systemic anaphylactic reaction in mice. RFRC dose-dependently decreased the IgE-mediated passive cutaneous anaphylaxis. In addition, RFRC decreased the gene expression and production of tumor necrosis factor-$\alpha$ (TNF-$\alpha$) and interleukin (IL)-6 in phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187 (A23187)-stimulated human mast cells. These findings provide evidence that RFRC could be a candidate as an anti-allergic agent.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.1
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• pp.117-124
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• 2017

The present study aimed to show that pro-inflammatory cytokines [tumor necrosis factor (TNF)-${\alpha}$, interferon (IFN)-${\gamma}$, and interleukin (IL)-$1{\beta}$] synergistically induce the production of nitric oxide (NO) production in mouse mesangial cells, which play an important role in inflammatory glomerular injury. We also found that co-treatment with cytokines at low doses (TNF-${\alpha}$; 5 ng/ml, IFN-${\gamma}$; 5 ng/ml, and IL-$1{\beta}$; 1.25 U/ml) synergistically induced NO production, whereas treatment with each cytokine alone did not increase NO production at doses up to 100 ng/ml or 50 U/ml. Silymarin, a polyphenolic flavonoid isolated from milk thistle (Silybum marianum), attenuates cytokine mixture (TNF-${\alpha}$, IFN-${\gamma}$, and IL-$1{\beta}$)-induced NO production. Western blot and RT-PCR analyses showed that silymarin inhibits inducible nitric oxide synthase (iNOS) expression in a dose-dependent manner. Silymarin also inhibited extracellular signal-regulated protein kinase-1 and -2 (ERK1/2) phosphorylation. Collectively, we have demonstrated that silymarin inhibits NO production in mouse mesangial cells, and may act as a useful anti-inflammatory agent.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.6
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• pp.1658-1663
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• 2006

Panax notoginseng (Buck) F.H chen. root (PNS) is used as a therapeutic agent to stop haemorrhages and a tonic to promote health in Korean and Chinses medicine. The pharmacokinetic profiles of the main PNS are still not accurately investigated. Our preliminary aim is to elucidate the pharmacokinetics features of the PNS in rats. Objective of this study is to determine whether PNS affects hepatic microvascular dysfunction elicited by gut ischemia and reperfusion (I/R), since gut I/R causes hepatic microvascular dysfunction, and to investigate the role of nitric oxide (NO). No has been found to be a modulator of the adhesive interactions between platelet and endothelial cells. Male Wistar rats were exposed to 30 min of gut ischemia followed by 60 min of reperfusion. Intravital microscopy was used to monitor the number of non-perfused sinusoids (NPS). In another set of experiments, PNS (1 g/kg pre day intragastrically) was administered to rats for 7 days. In some experiments, dexamethasone (ST) (2 mg/kg per day intravenously) was administered. In control rats, gut I/R elicited increases in the number of NPS, and plasma TNF-${\alpha}$ and ALT activities, and these changes were mitigated by the pretreatment with PNS. Pretreatment with an No synthase inhibitor diminished the protective effects of PNS on the increase in NPS and plasma TNF-${\alpha}$ levels, but not its effect on the increase in plasma ALT activities. Pretreatment with PNS increased plasma nitrite/nitrate levels. The responses caused by gut I/R were attenuated by the pretreatment with ST. Pretreatment with an NO synthase inhibitor did not affect the effect of ST. These results suggest that PNS attenuates the gut I/R-induced hepatic microvascular dysfunction and inflammatory responses such as TNF-${\alpha}$ production in the early phase via enhancement of NO production, and sequential hepatocellular damage via its anti-inflammatory effect like corticosteroid effect.

• Journal of Haehwa Medicine
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• v.14 no.2
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• pp.55-70
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• 2005

In oriental medicine, Gamibangpungtongsungsan (KBTS) has been used as a therapeutic agent for the treatments of acute stage of cerebrovascular diseases and hypertension. In the present study, underlying mechanism on KBTS effects was investigated using spontaneously hypertensive rats (SHR) by determining related parameters such as blood pressure, heart-beat rates, and hormones and plasma constituents. The major finding are summarized as follows. 1. KBTS treatment at concentrations lower than $125\;{\mu}g/m{\ell}$ did not show any cytotoxicity on cultured human fibroblast cells. 2. KBTS treatment in SHR significantly decreased blood pressure and heart-beat rate compared with untreated control. 3. KBTS treatment in SHR decreased aldosterone levels in the blood compared with untreated control, but the difference was not statistically significant. 4. KBTS treatment in SHR significantly decreased dopamine, norepinephrine and epinephrine levels in the blood compared with untreated control. 5. KBTS treatment in SHR decreased plasma ion concentrations such as Na+, K+, Ca2+, Cl- compared with untreated control; decreases in Na+ and Cl- were statistically significant. 6. KBTS treatment in SHR significantly decreased TNF-$\alpha$, IL-6, and IL-10 levels in the blood compared with untreated control. Thus, the present data show evidence on anti-hypertension activity of KBTS in an experimental animal system, which can provide further insights into the development of anti-hypertension therapeutic agents.

• Toxicological Research
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• v.20 no.4
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• pp.293-298
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• 2004

Background: Crohn's disease is characterized by a chronic relapsing inflammation of the bowel. Gliotoxin has been known to play strong immunosuppressive properties, while mechanisms for its anti-inflammatory actions are not completely understood. Here, we investigated the effects of gliotoxin in trinitrobenzene sulfonic acid (TNBS) induced mouse colitis, an animal model of Crohn's disease. Results: Gliotoxin dramatically improved clinical and histopathological symptoms in accompanied with reduced expression of TNF-$\alpha$, IL-1$\beta$, and ICAM-1 protein levels in TNBS induced colitis. Interestingly Gliotoxin induced Heme oxygenase-1 (HO-1) and the HO-1 inducer cobalt protoporphyrin IX (CoPPIX) completely mimicked the protective effects of gliotoxin in TNBS induced colitis mice. In contrast, the HO-1 inhibitor zinc protoporphyrin IX (ZnPPIX) could reverse the anti-inflammatory effects of gliotoxin and CoPPIX. Conclusions: Gliotoxin is a potential therapeutic agent targeting for the treatment of Crohn's disease by inducing HO-1.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2019.04a
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• pp.123-123
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• 2019

Xanthone is a kind of polyphenolic compounds that contain a distinctive chemical structure with a tricyclic aromatic ring found in a few higher plant families e.g. gentian root. This compound had a variety of biological activity, for instance antioxidant, antibacterial, anti-inflammatory, and anticancer effects. However, the effect of xanthone on mast cell-mediated allergic inflammation and its associated mechanism have not been elucidated. Therefore, the aim of this study was to elucidate the anti-allergic inflammatory effects and the underlying molecular mechanism of xanthone in PMACI-stimulated human mast cells-1 (HMC-1). In this result, xanthone treatment decreased the production of histamine, pro-inflammatory cytokines such as tumor necrosis factor-a (TNF-${\alpha}$), IL-6, and IL-8 and expressions of TSLP in PMACI-stimulated HMC-cells. In addition, xanthone significantly suppressed the phosphorylation of MAPKs and the activation of NF-${\kappa}B$ signal pathway in activated mast cells. Furthermore, xanthone inhibited the activation of caspase-1, an IL-$1{\beta}$ converting enzyme, in PMACI-stimulated HMC-1 cells. These findings provide evidence that xanthone could be a potential therapeutic agent for allergy-related inflammatory disorders.

• Biomolecules & Therapeutics
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• v.31 no.5
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• pp.536-543
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• 2023

Phytoceramide (Pcer) is found mainly in plants and yeast. It can be neuroprotective and immunostimulatory on various cell types. In this study, the therapeutic effect of Pcer was explored using the carrageenan/kaolin (C/K)-induced arthritis rat model and fibroblast-like synoviocytes (FLS). Pcer treatment (1, 10, and 30 mg/kg/day) were given to the arthritic rats for 6 days after disease induction. Weight distribution ration (WDR), knee thickness, squeaking score, serum levels of proinflammatory mediators, and histological analysis were measured and performed to evaluate arthritic symptoms in the rat model. In interleukin (IL)-1β-stimulated FLS, proinflammatory mediators were measured after Pcer (1-30 µM) treatment. Arthritic symptoms in rats with Pcer treatment were significantly decreased at days 4 to 6 after C/K arthritis induction. Inflammation in the knee joints were also significantly decreased in rats with Pcer treatment. Furthermore, in IL-1β-stimulated FLS, the expressions of proinflammatory mediators were also inhibited by Pcer. As shown by the results, Pcer has anti-arthritic effects in the C/K rat model and in synovial cells, suggesting that Pcer has the potential to be a useful agent in arthritis treatment.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.43 no.1
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• pp.39-45
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• 2010

Chlorella has been reported to have certain beneficial physiological effects, including hypocholesterolemic, antihypertensive, antioxidative, and anti-tumor activities in animal and human studies. The aim of this study was to determine the anti-inflammatory activities of an 80% methanol extract(CE-Met), hexane fraction (CE-Hex), and ethyl acetate fraction (CE-EA) of Chlorella ellipsoidea in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophage. Treatment with various concentrations of the C. ellipsoidea extract resulted m a significant, dose-dependent reduction in nitric oxide (NO) production by LPS-induced macrophages. The C. ellipsoidea extract significantly inhibited LPS-induced NO production accompanied by an attenuation of IL-6 and TNF-$\alpha$ formation in macrophages. These results suggest potent inhibit이y effects on the production of inflammatory mediators by a C. ellipsoidea extract. Thus, C. ellipsoidea extract may be a potent anti-inflammatory agent for troubled skin.

• Biomolecules & Therapeutics
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• v.21 no.4
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• pp.290-298
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• 2013

This study examined the effects of calcium (Ca) gluconate on collagen-induced DBA mouse rheumatoid arthritis (CIA). A single daily dose of 200, 100 or 50 mg/kg Ca gluconate was administered orally to male DBA/1J mice for 40 days after initial collagen immunization. To ascertain the effects administering the collagen booster, CIA-related features (including body weight, poly-arthritis, knee and paw thickness, and paw weight increase) were measured from histopathological changes in the spleen, left popliteal lymph node, third digit and the knee joint regions. CIA-related bone and cartilage damage improved significantly in the Ca gluconate-administered CIA mice. Additionally, myeloperoxidase (MPO) levels in the paw were reduced in Ca gluconate-treated CIA mice compared to CIA control groups. The level of malondialdehyde (MDA), an indicator of oxidative stress, decreased in a dose-dependent manner in the Ca gluconate group. Finally, the production of IL-6 and TNF-${\alpha}$, involved in rheumatoid arthritis pathogenesis, were suppressed by treatment with Ca gluconate. Taken together, these results suggest that Ca gluconate is a promising candidate anti-rheumatoid arthritis agent, exerting anti-inflammatory, anti-oxidative and immunomodulatory effects in CIA mice.