scholarly journals Preventive Effects of a Kampo Medicine, Kakkonto, on Inflammatory Responses via the Suppression of Extracellular Signal-Regulated Kinase Phosphorylation in Lipopolysaccharide-Treated Human Gingival Fibroblasts

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Hiroyuki Kitamura ◽  
Hiroko Urano ◽  
Toshiaki Ara
Keyword(s):  
Periodontal Disease ◽  
Inflammatory Responses ◽  
Human Gingival Fibroblasts ◽  
Kampo Medicine ◽  
Prostaglandin E ◽  
Gingival Fibroblasts ◽  
Extracellular Signal Regulated Kinase ◽  
Erk Phosphorylation ◽  
Extracellular Signal ◽  
Cox 2

Periodontal disease is accompanied by inflammation of the gingiva and destruction of periodontal tissues, leading to alveolar bone loss in severe clinical cases. The chemical mediator prostaglandin E2 (PGE2) and cytokines such as interleukin- (IL-)6 and IL-8 have been known to play important roles in inflammatory responses and tissue degradation. In the present study, we investigated the effects of a kampo medicine, kakkonto (TJ-1), on the production of prostaglandin E2 (PGE2), IL-6, and IL-8 by human gingival fibroblasts (HGFs) treated with lipopolysaccharide (LPS) from Porphyromonas gingivalis. Kakkonto concentration dependently suppressed LPS-induced PGE2 production but did not alter basal PGE2 levels. In contrast, kakkonto significantly increased LPS-induced IL-6 and IL-8 production. Kakkonto decreased cyclooxygenase- (COX-)1 activity to approximately 70% at 1 mg/mL but did not affect COX-2 activity. Kakkonto did not affect cytoplasmic phospholipase A2 (cPLA2), annexin1, or LPS-induced COX-2 expression. Kakkonto suppressed LPS-induced extracellular signal-regulated kinase (ERK) phosphorylation, which is known to lead to ERK activation and cPLA2 phosphorylation. These results suggest that kakkonto decreased PGE2 production by inhibition of ERK phosphorylation which leads to inhibition of cPLA2 phosphorylation and its activation. Therefore, kakkonto may be useful to improve gingival inflammation in periodontal disease.

scholarly journals Studies on Shokyo, Kanzo, and Keihi in Kakkonto Medicine on Prostaglandin E2 Production in Lipopolysaccharide-Treated Human Gingival Fibroblasts

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Toshiaki Ara ◽  
Norio Sogawa
Keyword(s):  
Inflammatory Responses ◽  
Human Gingival Fibroblasts ◽  
Prostaglandin E ◽  
Gingival Fibroblasts ◽  
Extracellular Signal Regulated Kinase ◽  
Annexin 1 ◽  
Cytosolic Phospholipase ◽  
Erk Phosphorylation ◽  
Extracellular Signal ◽  
Cox 2

We previously demonstrated that a kampo medicine, kakkonto, decreases lipopolysaccharide- (LPS-) induced prostaglandin E2 (PGE2) production by human gingival fibroblasts. In this study, we examined the herbs constituting kakkonto that exhibit this effect. Shokyo strongly and concentration dependently and kanzo and keihi moderately decreased LPS-induced PGE2 production. Shokyo did not alter cyclooxygenase-2 (COX-2) activity, cytosolic phospholipase A2 (cPLA2), annexin 1 and COX-2 expression, and LPS-induced extracellular signal-regulated kinase (ERK) phosphorylation. Kanzo inhibited COX-2 activity but increased annexin 1 and COX-2 expression and did not alter LPS-induced ERK phosphorylation. Keihi inhibited COX-2 activity and LPS-induced ERK phosphorylation but slightly increased COX-2 expression and did not alter cPLA2 and annexin 1 expression. These results suggest that the mechanism of shokyo is through the inhibition of cPLA2 activity, and that of kanzo and keihi is through the inhibition of COX-2 activity and indirect inhibition of cPLA2 activity. Therefore, it is possible that shokyo and kakkonto are clinically useful for the improvement of inflammatory responses.

scholarly journals Preventive Effects of a Kampo Medicine, Orento on Inflammatory Responses in Lipopolysaccharide Treated Human Gingival Fibroblasts

2010 ◽  
Vol 33 (4) ◽  
pp. 611-616 ◽  
Author(s):  
Toshiaki Ara ◽  
Ken-ichi Honjo ◽  
Yoshiaki Fujinami ◽  
Toshimi Hattori ◽  
Yasuhiro Imamura ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Human Gingival Fibroblasts ◽  
Kampo Medicine ◽  
Gingival Fibroblasts ◽  
Preventive Effects

scholarly journals Effects of shinbuto and ninjinto on prostaglandin E2 production in lipopolysaccharide-treated human gingival fibroblasts

2017 ◽  
Author(s):  
Toshiaki Ara ◽  
Norio Sogawa
Keyword(s):  
Arachidonic Acid ◽  
Prostaglandin E2 ◽  
Experimental Model ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Human Gingival Fibroblasts ◽  
Gingival Fibroblasts ◽  
Arachidonic Acid Cascade ◽  
Cytosolic Phospholipase ◽  
Cox 2

Previously, we revealed that several kampo medicines that are used for patients with excess and/or medium patterns [kakkonto (TJ-1), shosaikoto (TJ-9), hangeshashinto (TJ-14), and orento (TJ-120)] reduced prostaglandin (PG)E<2 levels using LPS-treated human gingival fibroblasts (HGFs). Recently, we examined other kampo medicines used for patients with the deficiency pattern [bakumondoto (TJ-29), shinbuto (TJ-30), ninjinto (TJ-32), and hochuekkito (TJ-41)] and the herbs comprising shinbuto and ninjinto using the same experimental model. Shinbuto and ninjinto concentration-dependently reduced LPS-induced PGE2 production by HGFs, whereas hochuekkito weakly reduced and bakumondoto did not reduce PGE2 production. Shinbuto and ninjinto did not alter cyclooxygenase (COX) activity or the expression of molecules involved in the arachidonic acid cascade. Therefore, we next examined which herbs compromising shinbuto and ninjinto reduce LPS-induced PGE2 production. Among these herbs, shokyo (Zingiberis Rhizoma) and kankyo (Zingiberis Processum Rhizoma) strongly and concentration-dependently decreased LPS-induced PGE2 production. However, both shokyo and kankyo increased the expression of cytosolic phospholipase (cPL)A2 but did not affect annexin1 or COX-2 expression. These results suggest that shokyo and kankyo suppress cPLA2 activity. We demonstrated that kampo medicines suppress inflammatory responses in patients with the deficiency pattern, and in those with excess or medium patterns. Moreover, kampo medicines that contain shokyo or kankyo are considered to be effective for the treatment of inflammatory diseases.

scholarly journals Effects of shinbuto and ninjinto on prostaglandin E2 production in lipopolysaccharide-treated human gingival fibroblasts

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e4120 ◽  
Author(s):  
Toshiaki Ara ◽  
Norio Sogawa
Keyword(s):  
Arachidonic Acid ◽  
Prostaglandin E2 ◽  
Experimental Model ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Human Gingival Fibroblasts ◽  
Gingival Fibroblasts ◽  
Arachidonic Acid Cascade ◽  
Cytosolic Phospholipase ◽  
Cox 2

Previously, we revealed that several kampo medicines used for patients with excess and/or medium patterns (kakkonto (TJ-1), shosaikoto (TJ-9), hangeshashinto (TJ-14), and orento (TJ-120)) reduced prostaglandin (PG)E2 levels using LPS-treated human gingival fibroblasts (HGFs). Recently, we examined other kampo medicines used for patients with the deficiency pattern [bakumondoto (TJ-29), shinbuto (TJ-30), ninjinto (TJ-32), and hochuekkito (TJ-41)] and the herbs comprising shinbuto and ninjinto using the same experimental model. Shinbuto and ninjinto concentration-dependently reduced LPS-induced PGE2 production by HGFs, whereas hochuekkito weakly reduced and bakumondoto did not reduce PGE2 production. Shinbuto and ninjinto did not alter cyclooxygenase (COX) activity or the expression of molecules involved in the arachidonic acid cascade. Therefore, we next examined which herbs compromising shinbuto and ninjinto reduce LPS-induced PGE2 production. Among these herbs, shokyo (Zingiberis Rhizoma) and kankyo (Zingiberis Processum Rhizoma) strongly and concentration-dependently decreased LPS-induced PGE2 production. However, both shokyo and kankyo increased the expression of cytosolic phospholipase (cPL)A2 but did not affect annexin1 or COX-2 expression. These results suggest that shokyo and kankyo suppress cPLA2 activity. We demonstrated that kampo medicines suppress inflammatory responses in patients with the deficiency pattern, and in those with excess or medium patterns. Moreover, kampo medicines that contain shokyo or kankyo are considered to be effective for the treatment of inflammatory diseases.

Mepivacaine-induced contraction involves phosphorylation of extracellular signal-regulated kinase through activation of the lipoxygenase pathway in isolated rat aortic smooth muscle

2013 ◽  
Vol 91 (4) ◽  
pp. 285-294 ◽  
Author(s):  
Hyo Min Lee ◽  
Seong-Ho Ok ◽  
Hui-Jin Sung ◽  
So Young Eun ◽  
Hye Jung Kim ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Nordihydroguaiaretic Acid ◽  
Rat Aorta ◽  
Dependent Manner ◽  
Aortic Smooth Muscle ◽  
Extracellular Signal Regulated Kinase ◽  
Erk Phosphorylation ◽  
Extracellular Signal ◽  
Cox 2 ◽  
Isolated Rat

Mepivacaine is an aminoamide local anesthetic with an intermediate duration that intrinsically produces vasoconstriction both in vivo and in vitro. This study investigated the arachidonic acid metabolic pathways involved in mepivacaine-induced contraction, and elucidated the associated cellular mechanism with a particular focus on extracellular signal-regulated kinase (ERK) in endothelium-denuded rat aorta. Isolated rat thoracic aortic rings were suspended for isometric tension recording. Cumulative mepivacaine concentration–response curves were generated in the presence or absence of the following inhibitors: quinacrine dihydrochloride, nordihydroguaiaretic acid, phenidone, AA-861, indomethacin, NS-398, SC-560, fluconazole, PD 98059, and verapamil. Mepivacaine-induced ERK phosphorylation, 5-lipoxygenase (5-LOX) expression, and cyclooxygenase (COX)-2 expression in rat aortic smooth muscle cells were detected by Western blot analysis in the presence or absence of inhibitors. Mepivacaine produced tonic contraction in isolated endothelium-denuded rat aorta. Quinacrine dihydrochloride, nordihydroguaiaretic acid, phenidone, AA-861, NS-398, PD 98059, and verapamil attenuated mepivacaine-induced contraction in a concentration-dependent manner. However, fluconazole had no effect on mepivacaine-induced contraction. PD 98059, quinacrine dihydrochloride, nordihydroguaiaretic acid, AA-861, phenidone, and indomethacin attenuated mepivacaine-induced ERK phosphorylation. Mepivacaine upregulated 5-LOX and COX-2 expression. These results suggest that mepivacaine-induced contraction involves ERK activation, which is primarily mediated by the 5-LOX pathway and in part by the COX-2 pathway.

scholarly journals Myricetin blocks lipoteichoic acid-induced COX-2 expression in human gingival fibroblasts

2014 ◽  
Vol 19 (1) ◽  
Author(s):  
Gloria Gutiérrez-Venegas ◽  
Oscar Luna ◽  
Juan Arreguín-Cano ◽  
Cristina Hernández-Bermúdez
Keyword(s):  
Infectious Disease ◽  
Septic Shock ◽  
Inflammatory Responses ◽  
Lipoteichoic Acid ◽  
Bacterial Toxins ◽  
Human Gingival Fibroblasts ◽  
Gingival Fibroblasts ◽  
Gram Positive Bacteria ◽  
Cox 2 ◽  
Bacterial Plaque

AbstractPeriodontitis is an infectious disease caused by microorganisms present in dental bacterial plaque. Lipoteichoic acid (LTA) is a component of the external membrane of Gram-positive bacteria. It causes septic shock. Ingested flavonoids have been reported to directly affect the regulation of cyclooxygenase-2 (COX-2) expression induced by bacterial toxins. In this study, we examined the effects of four flavonoids (luteolin, fisetin, morin and myricetin) on the activation of ERK1/2, p38 and AKT, and on the synthesis of COX-2 in human gingival fibroblasts treated with LTA from Streptococcus sanguinis. We found that luteolin and myricetin blocked AKT and p38 activation and that myricetin blocked LTA-induced COX-2 expression. The results of our study are important for elucidating the mechanism of action of flavonoid regulation of inflammatory responses.

Prostaglandin E2 Regulates Interleukin-1β-induced Matrix Metalloproteinase-3 Production in Human Gingival Fibroblasts

2004 ◽  
Vol 83 (3) ◽  
pp. 260-265 ◽  
Author(s):  
S.M.P.M. Ruwanpura ◽  
K. Noguchi ◽  
I. Ishikawa
Keyword(s):  
Matrix Metalloproteinase ◽  
Periodontal Disease ◽  
Prostaglandin E2 ◽  
Healthy Subjects ◽  
Human Gingival Fibroblasts ◽  
Interleukin 1Β ◽  
Prostaglandin E ◽  
Gingival Fibroblasts ◽  
Matrix Metalloproteinase 3 ◽  
Biological Actions

Prostaglandin E2 (PGE2) exerts its biological actions via EP receptors (EP1, EP2, EP3, and EP4). In the present study, we investigated whether PGE2 regulated interleukin (IL)-1β-induced matrix metalloproteinase (MMP)-3 production in human gingival fibroblasts (HGF) derived from periodontally healthy subjects and diseased patients. In HGF from healthy gingiva, PGE2 down-regulated IL-1β-induced MMP-3 production, whereas in HGF from periodontitis patients, PGE2 enhanced it. Butaprost (an EP2 agonist) and ONO-AE1-329 (an EP4 agonist) suppressed IL-1β-induced MMP-3 production, and 17-phenyl-ω-trinor PGE2 (an EP1 agonist) mimicked the PGE2 effect in HGF from healthy and periodontally diseased tissues, respectively. Analysis of these data suggests that, in HGF from healthy tissue, IL-1β-induced MMP-3 production is down-regulated by PGE2 via EP2 and EP4 receptors, whereas in cells from periodontally diseased tissue, IL-1β-induced MMP-3 production is up-regulated via EP1 receptors. Different regulation of IL-1β-induced MMP-3 production by PGE2 between healthy and periodontally diseased tissues may be involved in the pathogenesis of periodontal disease.

scholarly journals Preventive Effects of a Kampo Medicine, Shosaikoto, on Inflammatory Responses in LPS-Treated Human Gingival Fibroblasts

2008 ◽  
Vol 31 (6) ◽  
pp. 1141-1144 ◽  
Author(s):  
Toshiaki Ara ◽  
Yoshihiro Maeda ◽  
Yoshiaki Fujinami ◽  
Yasuhiro Imamura ◽  
Toshimi Hattori ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Human Gingival Fibroblasts ◽  
Kampo Medicine ◽  
Gingival Fibroblasts ◽  
Preventive Effects
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