• Biomolecules & Therapeutics
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• v.2 no.2
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• pp.149-154
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• 1994

Anti-allergic and anti-inflammatory actions of the water extract from Cimicifuga heracleifolia were evaluated in mice and rats. Several criteria were employed to assess the anti-allergic and anti-inflammatory actions of Cimicifuga heracleifolia, such as hyaluronidase activity, mediators-induced vascular permeability changes, 48 hour homologous passive cutaneous anaphylaxis (PCA) histamine release from mast cells, and the carrageenan-induced rat paw edema. To further characterize the active components, the water extract was either extracted with organic solvent or fractionated according to molecular weight, and each fraction was tested for some of anti-allergic parameters. Hyaluronidase activities, both in activating and in activated states, were significantly inhibited by the water extract of Cimicifuga heracleifolia and by some of its subfractions, molecular weight less than 1,000. The water extracts (50~400 mg/kg) significantly inhibited 48 hr homologous PCA and vascular permeability changes induced by chemical mediators (histamine, serotonin, and leukotriene $C_4$) in mice. In the case of histamine-induced vascular permeability changes, more extensive studies were conducted; water extract was either fractionated according to molecular weight or extracted with butanol. Anti-histamine actions were observed only from the water layer, and these active components were of the molecular weight less than 1,000. These anti-allergic actions were observed mainly from mice than from rats. On the other hand, anti-inflammatory actions of the water extract from Cimicifuga heracleifolia were significant in rats.

• Biomolecules & Therapeutics
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• v.12 no.3
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• pp.145-150
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• 2004

Inflammation is a frequent radiation-induced reaction following therapeutic irradiation. Treatment of human umbilical endothelial cells (HUVEC) with ${\gamma}$-irradiation (${\gamma}$IR) induces the expression of adhesion proteins such as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. Since the upregulation of these proteins on endothelial cell Surface has been known to be associated with inflammation, interfering with the expression of adhesion molecules is an important therapeutic target. In the present study, we demonstrate that vitamin C inhibits ${\gamma}$IR induced expression of ICAM-1, VCAM-1, and E-selectin on HUVEC in a dose- and time dependent manner. Vitamin C a1so inhibited the production of Nitric oxide (NO) induced by ${\gamma}$IR. These data suggest that vitamin C has therapeutic potential for the treatment of various inflammatory disorder associated with an increase of endothelial leukocyte adhesion molecules.

• YAKHAK HOEJI
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• v.47 no.5
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• pp.325-330
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• 2003

Solanum melongena L. (Solanaceae) has anti-oxidant, analgesic, and hypolipidemic effects. We previously showed that Solanum melongena (SM) aqueous extract inhibits mast cell-mediated allergic reactions. The activation of protease-activated receptor-2 (PAR-2) induces acute inflammation in rat hindpaw. In the present study, we investigated the effects of the SM aqueous extract on mouse paw edema induced by PAR2 agonists. Trypsin or trans-cinnamoyl-LIGRLO-NH$_2$ (tc-NH$_2$), PAR-2 agonists, was injected into the hind paw of mice to induce paw edema. SM aqueous extract (1, 5, 10, and 100 mg/kg) was orally administered 1 hr before induction of paw edema. SM aqueous extract (5, 10, and 100 mg/kg) significantly inhibited both paw edema and vascular permeability in the dose-dependent manner. Furthermore, SM aqueous extract (10 mg/kg) significantly inhibited PAR-2 agonist-induced myeloperoxidase (MPO) activity and tumor necrosis factor (TNF)-$\alpha$ expression in paw tissue compared to that of saline. These results suggest that SM aqueous extract may be useful for treatment of PAR-2-mediated inflammation.

• BMB Reports
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• v.52 no.11
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• pp.665-670
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• 2019

Nucleotide-binding oligomerization domain protein 2 (NOD2), an intracellular pattern recognition receptor, plays important roles in inflammation and cell death. Previously, we have shown that NOD2 is expressed in vascular smooth muscle cells (VSMCs) and that NOD2 deficiency promotes VSMC proliferation, migration, and neointimal formation after vascular injury. However, its role in endoplasmic reticulum (ER) stress-induced cell death in VSMCs remains unclear. Thus, the objective of this study was to evaluate ER stress-induced viability of mouse primary VSMCs. NOD2 deficiency increased ER stress-induced cell death and expression levels of apoptosis mediators (cleaved caspase-3, Bax, and Bak) in VSMCs in the presence of tunicamycin (TM), an ER stress inducer. In contrast, ER stress-induced cell death and expression levels of apoptosis mediators (cleaved caspase-3, Bax, and Bak) were decreased in NOD2-overexpressed VSMCs. We found that the $IRE-1{\alpha}-XBP1$ pathway, one of unfolded protein response branches, was decreased in NOD2-deficient VSMCs and reversed in NOD2-overexpressed VSMCs in the presence of TM. Furthermore, NOD2 deficiency reduced the expression of XBP1 target genes such as GRP78, PDI-1, and Herpud1, thus improving cell survival. Taken together, these data suggest that the induction of ER stress through NOD2 expression can protect against TM-induced cell death in VSMCs. These results may contribute to a new paradigm in vascular homeostasis.

• The Korean Journal of Physiology and Pharmacology
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• v.28 no.5
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• pp.449-456
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• 2024

Vascular smooth muscle cells (VSMCs) under biophysical stress play an active role in the progression of vascular inflammation, but the precise mechanisms are unclear. This study examined the cellular expression of monocyte chemoattractant protein 1 (MCP-1) and its related mechanisms using cultured rat aortic VSMCs stimulated with mechanical stretch (MS, equibiaxial cyclic stretch, 60 cycles/min). When the cells were stimulated with 10% MS, MCP-1 expression was markedly increased compared to those in the cells stimulated with low MS intensity (3% or 5%). An enzyme-linked immunosorbent assay revealed an increase in HMGB1 released into culture media from the cells stimulated with 10% MS compared to those stimulated with 3% MS. A pretreatment with glycyrrhizin, a HMGB1 inhibitor, resulted in the marked attenuation of MCP-1 expression in the cells stimulated with 10% MS, suggesting a key role of HMGB1 on MCP-1 expression. Western blot analysis revealed higher PDGFR-α and PDGFR-β expression in the cells stimulated with 10% MS than 3% MS-stimulated cells. In the cells deficient of PDGFR-β using siRNA, but not PDGFR-α, HMGB1 released into culture media was significantly attenuated in the 10% MS-stimulated cells. Similarly, MCP-1 expression induced in 10% MS-stimulated cells was also attenuated in cells deficient of PDGFR-β. Overall, the PDGFR-β signaling plays a pivotal role in the increased expression of MCP-1 in VSMCs stressed with 10% MS. Therefore, targeting PDGFR-β signaling in VSMCs might be a promising therapeutic strategy for vascular complications in the vasculatures under excessive biophysical stress.

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.1
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• pp.61-66
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• 2010

Inflammation is a double-edge sword, functioning as a response against external stimuli, but excessive inflammation can lead to a harmful result. Inflammation is important in the development of vascular diseases, such as atherosclerosis and restenosis. Sohamhyung-tang(SHHT) is one of major herbal prescriptions from "Sanghanron", treating congested heat in thorax. It can be seen as an origin of several prescriptions for Hyungbi(胸痺, thoracic congestion), with its major component Trichosanthes semen. This study was done to determine whether SHHT reduces the production of nitrite, index of NO, and pro-inflammatory cytokines in Lipopolysaccharide(LPS)-induced RAW 264.7 cells. The results show that SHHT inhibited LPS-induced production of NO and PGE2, and iNOS and COX-2 expression, meaning SHHT has a significant anti-inflammatory effect. Based on these results, we suggest that SHTT can be used for prevention and treatment of diseases which starts from chronic inflammatory reactions.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.15 no.2
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• pp.33-52
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• 2002

The effects of Arctii fructus extract on allegenic inflammation were investigated using in vivo and in vitro test models. Firstly, the cytotoxicity of Arctii fructus extract was validated using MTT assay. As a result, Arctii fructus extract showed no cytotoxic potential, while SDS, a positive control, revealed strong cytotoxic effect. In LLNA assay, Arctii fructus extract showed no skin allergenicity. Next, the anti-allergic actions of Arctii fructus extract were evaluated using rodent experimental models. The oral, intraperitoneal and intradermal administration of Arctii fructus extract significantly inhibited the compound 48／80-induced vascular permeability documented by Evans blue extravasation. In addition, Arctii fructus extract showed potent inhibitory effect on passive cutaneous anaphylaxis activated by anti-dinitrophenyl (DNP) IgE when orally administered. In an in vitro study, Arctii fructus extract revealed to possess inhibitory potential on the compound 48／80-induced histamine release from rat peritoneal mast cells. Moreover, Arctii fructus extract inhibited the IL-4 and TNF-${\alpha}$ mRNA induction by PMA and A23187 in human leukemia mast cells, HMC-1. Finally, it revealed that Arctii fructus extract significantly suppressed histamin-provoked antigenic inflammation reactions in human prick test. Taken together, these results suggest that anti-allergic action of Arctii fructus extract may be due to the inhibition of histamine release and cytokine gene expression in the mast cells.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.05a
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• pp.1-8
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• 2001

Increased expression of inducible cyclo-oxygenase (COX-2) is associated with a wide variety of tumours. In addition inhibitors of COX have shown a great deal of promise in vitro and in animal models as potential anti-tumour therapies. COX enzymes utilise the substrate arachidonic acid to produce prostaglandin (PO)H$_2$, the precursor to all the prostanoids.(omitted)

• Proceedings of the Korean Society of Veterinary Pathology Conference
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• 2002.11a
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• pp.66-79
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• 2002

The basic treatments - Epithelial ＆ stromal debridement with a swab or diamond burr. - Possible placement of a collagen shield or nictitans flap. - Topical treatment with Adequan IM diluted in artificial tears : 1 ml Adequan + 4 ml tears : One drop four times daily. - Topical treatment with an antibiotic drop : Three times daily - 5％ sodium chloride ointment : Four times daily. If inflammation is severe - Topical treatment with nonsteroidal agent : Four times daily (Voltaren, Ocufen, or Profenyl) - Cyclosporine A (Optimmune) : Twice daily Healing time - Healing typically occurs rapidly - Fluorescein negative : 7-10 days - Vascular keratitis : Often several months

• The Korean Journal of Physiology and Pharmacology
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• v.28 no.5
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• pp.469-478
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• 2024

Chronic intermittent hypoxia (CIH) can lead to vascular dysfunction and increase the risk of cardiovascular diseases, cerebrovascular diseases, and arterial diseases. Nevertheless, mechanisms underlying CIH-induced vascular dysfunction remain unclear. Herein, this study analyzed the role of aortic smooth muscle calcium-activated potassium (BK) channels in CIH-induced vascular dysfunction. CIH models were established in rats and rat aortic smooth muscle cells (RASMCs). Hemodynamic parameters such as mean blood pressure (MBP), diastolic blood pressure (DBP), and systolic blood pressure (SBP) were measured in rats, along with an assessment of vascular tone. NO and ET-1 levels were detected in rat serum, and the levels of ET-1, NO, eNOS, p-eNOS, oxidative stress markers (ROS and MDA), and inflammatory factors (IL-6 and TNF-α) were tested in aortic tissues. The Ca²⁺ concentration in RASMCs was investigated. The activity of BK channels (BKα and BKβ) was evaluated in aortic tissues and RASMCs. SBP, DBP, and MBP were elevated in CIH-treated rats, along with endothelial dysfunction, cellular edema and partial detachment of endothelial cells. BK channel activity was decreased in CIH-treated rats and RASMCs. BK channel activation increased eNOS, p-eNOS, and NO levels while lowering ET-1, ROS, MDA, IL-6, and TNF-α levels in CIH-treated rats. Ca²⁺ concentration increased in RASMCs following CIH modeling, which was reversed by BK channel activation. BK channel inhibitor (Iberiotoxin) exacerbated CIH-induced vascular disorders and endothelial dysfunction. BK channel activation promoted vasorelaxation while suppressing vascular endothelial dysfunction, inflammation, and oxidative stress, thereby indirectly improving CIH-induced vascular dysfunction.