• Journal of Yeungnam Medical Science
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• 제34권1호
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• pp.43-54
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• 2017

Background: Extracellular sulfatases (Sulfs), sulfatase 1 (Sulf1) and sulfatase 2 (Sulf2), play a pivotal role in cell signaling by remodeling the 6-O-sulfation of heparan sulfate proteoglycans on the cell surface. The present study examined the effects of Sulfs on angiotensin II (Ang II)-induced hypertensive mediator expression and vascular smooth muscle cells (VSMCs) proliferation in spontaneously hypertensive rats (SHR). Methods: Ang II receptors, 12-lipoxygenase (12-LO), and endothelin-1 (ET-1) messenger RNA (mRNA) expressions in SHR VSMCs were analyzed by real-time polymerase chain reaction and Western blotting. VSMCs proliferation was determined by [$^3H$]-thymidine incorporation. Results: Basal Sulfs mRNAs expression and enzyme activity were elevated in SHR VSMCs. However, Sulfs had no effect on the basal or Ang II-induced 12-LO and ET-1 mRNA expression in SHR VSMCs. The inhibition of Ang II-induced 12-LO and ET-1 expression by blockade of the Ang II type 2 receptor ($AT_2\;R$) pathway was not observed in Sulf1 siRNA-transfected SHR VSMCs. However, Sulf2 did not affect the action of $AT_2\;R$ inhibitor on Ang II-induced 12-LO and ET-1 expression in SHR VSMCs. The down-regulation of Sulf1 induced a reduction of $AT_2\;R$ mRNA expression in SHR VSMCs. In addition, the inhibition of Ang II-induced VSMCs proliferation by blockade of the $AT_2\;R$ pathway was mediated by Sulf1 in SHR VSMCs. Conclusion: These findings suggest that extracellular sulfatase Sulf1 plays a modulatory role in the $AT_2\;R$ pathway that leads to an Ang II-induced hypertensive effects in SHR VSMCs.

• Biomolecules & Therapeutics
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• 제20권6호
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• pp.526-531
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• 2012

During our on-going studies to identify bioactive compounds in medicinal herbs, we found that saucerneol F (SF), a naturally occurring sesquilignan isolated from Saururus chinensis (S. chinensis), showed in vitro anti-inflammatory activity. In this study, we examined the effects of SF on the generation of 5-lipoxygenase (5-LO) dependent leukotriene $C_4$ ($LTC_4$), cyclooxygenase-2 (COX-2) dependent prostaglandin $D_2$ ($PGD_2$), and on phospholipase $C{\gamma}1$ ($PLC{\gamma}1$)-mediated degranulation in SCF-induced mouse bone marrow-derived mast cells (BMMCs). SF inhibited eicosanoid ($PGD_2$ and $LTC_4$) generation and degranulation dose-dependently. To identify the molecular mechanisms underlying the inhibition of eicosanoid generation and degranulation by SF, we examined the effects of SF on the phosphorylation of $PLC{\gamma}1$, intracellular $Ca^{2+}$ influx, the translocation of cytosolic phospholipase $A_2$ ($cPLA_2$) and 5-LO, and on the phosphorylation of MAP kinases (MAPKs). SF was found to reduce intracellular $Ca^{2+}$ influx by inhibiting $PLC{\gamma}1$ phosphorylation and suppressing the nuclear translocations of $cPLA_2$ and 5-LO via the phosphorylations of MAPKs, including extracellular signal-regulated protein kinase-1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38. Taken together, these results suggest that SF may be useful for regulating mast cell-mediated inflammatory responses by inhibiting degranulation and eicosanoid generation.

• Biomolecules & Therapeutics
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• 제23권5호
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• pp.421-427
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• 2015

Imperatorin has been known to exert many biological functions including anti-inflammatory activity. In this study, we investigated the inhibitory effects of imperatorin on the production of inflammatory mediators in mouse bone marrow-derived mast cells (BMMC). Imperatorin inhibited degranulation and the generation of eicosanoids (leukotriene $C_4$ ($LTC_4$) and prostaglandin $D_2$ ($PGD_2$) in IgE/antigen (Ag)-stimulated BMMC. To elucidate the molecular mechanism involved in this process, we investigated the effect of imperatorin on intracellular signaling in BMMC. Biochemical analyses of the IgE/Ag-mediated signaling pathway demonstrated that imperatorin dramatically attenuated degranulation and the production of 5-lipoxygenase-dependent $LTC_4$ and cyclooxygenase-2-dependent $PGD_2$ through the inhibition of intracellular calcium influx/phospholipase $C{\gamma}1$, cytosolic phospholipase $A_2$/mitogen-activated protein kinases and/or nuclear factor-${\kappa}B$ pathways in BMMC. These results suggest that the effects of imperatorin on inhibition of degranulation and eicosanoid generation through the suppression of multiple steps of IgE/Ag-mediated signaling pathways would be beneficial for the prevention of allergic inflammation.

• Natural Product Sciences
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• 제22권4호
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• pp.225-230
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• 2016

Phytochemical investigation from the stem bark of Beilschmiedia pulverulenta resulted in the isolation of five lignans, (+)-yangambin (1), (+)-sesartemin (2), (+)-excelsin (3), (+)-sesamin (4), and (+)-syringaresinol (5), together with lupeol (6), lupenone (7), ${\beta}-sitosterol$ (8), and ${\beta}-sitostenone$ (9). Their structures were established by the analysis of their spectroscopic (1D and 2D NMR) and spectrometric (MS) data, as well as by comparison with those reported in the literature. The isolated lignans were tested for their anticholinesterase (AChE: acetylcholine esterase and BChE: butyryl cholineesterase) and anti-inflammatory (COX-2: cyclooxygenase-2 and LOX: lipoxygenase) activities. All the isolated lignans (1 - 5) exhibited significant inhibition activities in AChE/BChE and COX-2/LOX assays with $IC_{50}$ values ranging from $168.8-504.2{\mu}M$ and $21.0-59.4{\mu}M$, respectively.

• Environmental Analysis Health and Toxicology
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• 제14권3호
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• pp.95-101
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• 1999

The scavenging effects of two hyaroxycinnamic acids such as caffeic acid and chlorogenic acid on paraquat induced pulmonary toxicity were investigated. The results are summerized as follows: 1. In the 5-lipoxygenase assay, caffeic acid and chlorogenic acid inhibited the enzyme activities whose inhibition concentration (IC$\_$50/) were 4.1 and 9.6 ${\mu}$M respectively. 2. To evaluate the antiinflammatory effects on mediator related to the mechanism of inflammation, ADP-induced platelet aggregation assay and histamine degranulation assay were used. Caffeic acid and chlorogenic acid inhibited on ADP-induced platelet aggregation and histamine release at a concentration dependent manners. 3. Arachidonic acid-induced ear edema were inhibited by administration of caffeic acid and chlorogenic acid. 4. Cytologicad analysis of branchoalveolar lavage fluid (BALF) which was the useful tool for detection of an inflammatory response in the lungs of animals intoxicated with chemicals were used. Alveolar macrophages and neutrophils in BALF, as well as the protein content and the LDH activity in BALF supernatant increased by intoxication of paraquat, but decreased by administration of caffeic acid and chlorogenic acid. Therefore, two hydroxyeinnamic acids tested were the useful candidates for scavenger and antiinflammatory agents on paraquat induced pulmonary toxicity.

• Nutritional Sciences
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• 제9권3호
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• pp.152-158
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• 2006

Helicobacter pylori (H. pylori) infection rapidly stimulated either COX-2 or 5-LOX and released arachidonic acid metabolites that have been considered as pivotal mediators in H. pylori-induced inflammatory responses. To determine whether red ginseng extract (RGE) can suppress the biosynthesis of 5(S)-hydroxyeicosatetraenoic acids (HETE), a precursor metabolite of leukotrienes B4 (LTB4) in H. pylori-provoked inflammatory responses in gastric epithelial cells, the biosynthesis of monohydroxy fatty acids was measured using radioactive arachidonic acid and validated by RP-HPLC using non-radioactive AA as substrate in AGS cells cocultured with H. pylori (ATCC 43504) with or without pretreatment of RGE. Among three known major HETEs, H. pylori infection specifically induced the biosynthesis of $^{14}C-5(S)-HETE$ rather than the complex of $^{14}C-15S-/^{14}C-12(S)-HETE$ from $^{14}C-AA$, concomitantly obtained by HPLC(p<0.01). RGE, 1 to $100{\mu}g/ml$, selectively suppressed H. pylori-stimulated $^{14}C-5(S)-HETE$ production implying the attenuation of 5-lipoxygenase activity, of which was similar to known LOX inhibitor NDGA $(10{\mu}M)$ (p<0.01). However, the amount of 5(S)-HETE was significantly reduced by higher dose of RGE $(100{\mu}g/ml)$ (p<0.05). These results indicated that LOX pathway might be one of principle pathogenic mechanisms of H. pylori and red ginseng could be a nutraceutical against H. pylori infection through inhibiting action of LOX activity.

• 동의생리병리학회지
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• 제20권5호
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• pp.1295-1302
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• 2006

Our preliminary aim is to elucidate the pharmacokinetic features of the PNS(Panax notoginseng Buck F.H. Chen. (Arialiaceae) root). First, we assessed the prevention of neurtrophil functions. A Panax notoginseng inhibited neutrophil functions, including degranulation, superoxide generation, and leukotriene B4 production, without any effect on 5-lipoxygenase activity. This Panax notoginseng reduced nitric oxide (NO) and prostaglandin E2 production in mouse peritoneal macrophages stimulated with lipopolysaccharide, whereas no influence on the activity of inducible NO synthase, cyclo-oxygenase-2 or cyclo-oxygenase-1 was observed. Panax notoginseng significantly reduced mouse paw oedema induced by carrageenan. The results indicate that Panax notoginseng exerts anti-inflammatory effects related to the inhibition of neutrophil functions and of NO and prostaglandin E2 production, which could be due to a decreased expression of inducible NO synthase and cyclo-oxygenase-2.

• Journal of Microbiology and Biotechnology
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• 제31권6호
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• pp.847-854
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• 2021

Platycodon grandiflorum (balloon flower) root (Platycodi radix, PR) is used as a health supplement owing to its beneficial bioactive properties. In the present study, the anti-inflammatory, antioxidant, and whitening effects of deglycosylated platycosides (saponins) from PR biotransformed by pectinase from Aspergillus aculeatus were investigated. The bioactivities of the platycosides improved when the number of sugar moieties attached to the aglycone platycosides was decreased. The deglycosylated saponins exhibited higher lipoxygenase inhibitory activities (anti-inflammatory activities) than the precursor platycosides and the anti-inflammatory compound baicalein. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity of the pectinasetreated PR extract was higher than that of the non-treated PR extract. The trolox-equivalent antioxidant capacity (TEAC) assay showed improved values as the saponins were hydrolyzed. The tyrosinase inhibitory activities (whitening effects) of deglycosylated platycosides were higher than those of the precursor platycosides. Furthermore, 3-O-β-ᴅ-glucopyranosyl platycosides showed higher anti-inflammatory, antioxidant, and whitening activities than their precursor glycosylated platycosides. Therefore, 3-O-β-ᴅ-glucopyranosyl platycosides may improve the beneficial effects of nutritional supplements and cosmetic products.

• 생약학회지
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• 제30권4호
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• pp.377-383
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• 1999

The anti-asthmatic activities of the extract of Lonicera japonica (BuOH fraction) and its mode of action were investigated using several in vitro and in vivo models. Lonicera japonica was extracted with 30% ethanol (v/v) and successively partitioned into BuOH. The BuOH fraction reduced antigen-induced contraction of isolated trachea from sensitized guinea pigs in a concentration-dependent manner. The BuOH fraction also inhibited histamine release from rat peritoneal mast cells induced by antigen or calcium ionophore A23187 ($IC_{50}=0.26$ and 0.32mg/ml, respectively). Eosinophil infiltration into bronchoalveolar lavage fluids induced by aeroallergen challenge in passively sensitized guinea pigs was inhibited by the BuOH fraction at a dose of 800mg/kg (51.7%). In addition, the BuOH fraction inhibited leukotriene $B_4$ prodution in rat basophilic leukemia cells ($IC_{50}=0.42\;mg/ml$) as well as phosphodiesterase 4 (PDE4) isolated from rat brain ($IC_{50}=0.015\;mg/ml$). All results from this study strongly suggest that the BuOH fraction of Lonicera japonica may be useful in the treatment of asthma and its mode of action may be related with inhibition of both 5-lipoxygenase and PDE4 enzyme.

• 한국임상수의학회지
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• 제33권4호
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• pp.194-199
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• 2016

The objective of this study was to examine the effect of trans-10, cis-12 conjugated linoleic acid (t10c12-CLA) on the expression of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) pathway in lipopolysaccharide (LPS)-stimulated porcine peripheral blood mononuclear cells (PBMCs). t10c12-CLA was treated with different concentrations in culture medium of LPS$na{\ddot{i}}ve$ and LPS-stimulated PBMCs. The mRNA expressions of prostaglandin $E_2$ ($PGE_2$)-synthase, COX-2 and 5-LOX were measured using quantitative real-time PCR. In addition, the production levels of $PGE_2$ and 5-LOX in culture supernatant from PBMCs with or without LPS were assessed by ELISA. In LPS$na{\ddot{i}}ve$ PBMCs, treatment of t10c12-CLA significantly (p < 0.05) increased the mRNA expressions of PGE2 synthase and 5-LOX compared to vehicle control. Expression of COX-2 mRNA did not show significant difference compared to vehicle control by t10c12-CLA treatment in LPS$na{\ddot{i}}ve$ PBMCs. However, the addition of LPS in PBMCs markedly (p < 0.05) increased the mRNA expression of COX-2, $PGE_2$ synthase and 5-LOX, and also significantly (p < 0.05) enhanced the production of $PGE_2$ and 5-LOX relative to LPS$na{\ddot{i}}ve$ PBMCs, respectively. However, the addition of t10c12-CLA significantly (p < 0.01) suppressed the LPS-induced excessive expression of COX-2, $PGE_2$ synthase, and 5-LOX compared to those of PBMCs treated with LPS alone. The production levels of $PGE_2$ and 5-LOX in culture supernatant from LPS-stimulated PBMCs were also significantly (p < 0.05) inhibited by the treatment of t10c12-CLA compared to LPS alone. These results suggested that t10c12-CLA has an anti-inflammatory effect via dual inhibition of COX-2 and 5-LOX with gene expression and production level in LPS-stimulated porcine PBMCs. Therefore, it was thought that t10c12-CLA can attenuate the inflammatory response by down-regulation of eicosanoids production.