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

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 phospholipaseA2 (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

LPS 刺激ヒト歯肉線維芽細胞におけるExtracellular Signal-Regulated Kinase のリン酸化抑制を介した葛根湯の炎症反応抑制効果

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 LPSinduced IL-6 and IL-8 production. Kakkonto decreased cyclooxygenase- (COX-)1 activity to approximately 70% at 1mg/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.2014博士（歯学）松本歯科大

Nutrient intake if matsumoto dental university students -analysis using BDHQ-

A brief diet history questionnaire was issued to first–year Japanese students (１8–29 years old) at the School of Dentistry of Matsumoto Dental University to determine their nutrient and food intakes for future nutrition education programs. The subjects of this study were １96 people (１38 males, 58 females). １) The contribution of protein, particularly of plant origin, to energy intake was significantly higher in female than in male students. 2) Compared with men, women had significantly higher intakes (weight per １,000 kcal) of minerals (sodium, potassium, calcium, magnesium, phosphorus, iron, and copper), fat–soluble vitamins (β–carotene equivalents and vitamin E [ α–tocopherol]), water–soluble vitamins (B １ , B 2 , B 6 , folic acid, pantothenic acid, and C), cholesterol, and fiber. 3) In terms of food–group intake (weight per １,000 kcal), a significantly higher intake in men than in women was only observed for grains. Consistent with the energy and nutrient intakes, dietary intakes of legumes, dark–colored vegetables, other (light–colored) vegetables, fruits, and sweets/snacks were significantly higher in women. In this survey, differences in nutrient and food intakes were noted in male and female students. In general, it was shown that female students eat a more varied and nutrient–richer diet

リポ多糖類処理を行ったヒト歯肉線維芽細胞の炎症反応に対する漢方薬半夏瀉心湯の予防効果

In the present study, we investigated the effects of a Kampo medicine hangeshashinto (TJ-14) on the production of prostaglandin E2 (PGE2), interleukin (IL)-6 and IL-8 by human gingival fibroblasts (HGFs) treated with lipopolysaccharide (LPS) from Porphyromonas gingivalis. HGFs proliferation was dose-dependently decreased with hangeshashinto at days 3 and 7. However, treatment with LPS (10 ng/ml), hangeshashinto (up to 1 mg/ml) and their combinations for 24 h did not affect the viability of HGFs. Hangeshashinto dose-dependently suppressed LPS-induced PGE2 production but did not alter basal PGE2 level. Hangeshashinto weakly decreased LPS-induced IL-6 and IL-8 productions. Hangeshashinto decreased cyclooxygenase (COX)-1 and COX-2 activities to approximately 60% at 1 mg/ml. Hangeshashinto decreased cytoplasmic phospholipase A2 (cPLA2) expression and LPS-induced COX-2 expression but not affected annexin1 expression. Hangeshashinto weakly suppressed LPS-induced extracellular signal-regulated kinase (ERK) phosphorylation, which is known to lead to ERK activation and cPLA2 phosphorylation. These results suggest that hangeshashinto decreased PGE2 production by (1) suppression of cPLA2 and LPS-induced COX-2 expression, and to a lesser extent, (2) inhibition of COX-2 activity and (3) inhibition of cPLA2 phosphorylation and its activation via inhibition of ERK phosphorylation. Moreover, it is also suggested that hangeshashinto may be useful to improve gingival inflammation in periodontal disease

Protein kinase A enhances lipopolysaccharideinduced IL-6, IL-8, and PGE2 production by human gingival broblasts

Objective: Periodontal disease is accompanied by inflammation of the gingiva and destruction of periodontaltissues, leading to alveolar bone loss in severe clinical cases. Interleukin (IL)-6, IL-8, and the chemical mediatorprostaglandin E2 (PGE2) are known to play important roles in inflammatory responses and tissue degradation.Recently, we reported that the protein kinase A (PKA) inhibitor H-89 suppresses lipopolysaccharide (LPS)-inducedIL-8 production by human gingival fibroblasts (HGFs). In the present study, the relevance of the PKA activity andtwo PKA-activating drugs, aminophylline and adrenaline, to LPS-induced inflammatory cytokines (IL-6 and IL-8) andPGE2 by HGFs were examined.Methods: HGFs were treated with LPS from Porphyromonas gingivalis and H-89, the cAMP analog dibutyryl cyclicAMP (dbcAMP), aminophylline, or adrenaline. After 24 h, IL-6, IL-8, and PGE2 levels were evaluated by ELISA.Results: H-89 did not affect LPS-induced IL-6 production, but suppressed IL-8 and PGE2 production. In contrast,dbcAMP significantly increased LPS-induced IL-6, IL-8, and PGE2 production. Up to 10 μg/ml of aminophylline didnot affect LPS-induced IL-6, IL-8, or PGE2 production, but they were significantly increased at 100 μg/ml. Similarly,0.01 μg/ml of adrenaline did not affect LPS-induced IL-6, IL-8, or PGE2 production, but they were significantlyincreased at concentrations of 0.1 and 1 μg/ml. In the absence of LPS, H-89, dbcAMP, aminophylline, andadrenaline had no relevance to IL-6, IL-8, or PGE2 production.Conclusion: These results suggest that the PKA pathway, and also PKA-activating drugs, enhance LPS-induced IL-6,IL-8, and PGE2 production by HGFs. However, aminophylline may not have an effect on the production of thesemolecules at concentrations used in clinical settings (8 to 20 μg/ml in serum). These results suggest thataminophylline does not affect inflammatory responses in periodontal disease

Effects of shokyo (Zingiberis Rhizoma) and kankyo (Zingiberis Processum Rhizoma) on prostaglandin E2 production in lipopolysaccharide-treated mouse macrophage RAW264.7 cells

We previously reported that shokyo and kankyo, which are water-extracted fractions of ginger, reduced LPS-induced PGE2 production in human gingival fibroblasts. In this study, we examined the effects of these herbs on LPS-treated mouse macrophage RAW264.7 cells. Both shokyo and kankyo reduced LPS-induced PGE2 production in a concentration-dependent manner. Shokyo and kankyo did not inhibit cyclooxygenase (COX) activity, nor did they alter the expression of molecules in the arachidonic acid cascade. In addition, these herbs did not alter NF-κB p65 translocation into nucleus, or phosphorylation of p65 or ERK. These results suggest that shokyo and kankyo inhibit cPLA2 activity. Although 6-shogaol produced similar results to those of shokyo and kankyo, the concentration of 6-shogaol required for the reduction of PGE2 production were higher than those of 6-shogaol in shokyo and kankyo. Therefore, several gingerols and shogaols other than 6-shogaol may play a role in the reduction of LPS-induced PGE2 production. Thus, 6-shogaol, and other gingerols and shogaols inhibit cPLA2 activity and reduce LPS-induced PGE2 production via a different mechanism from traditional anti-inflammatory drugs. Moreover, kampo medicines that contain shokyo or kankyo are considered to be effective for inflammatory diseases

The Biological Efficacy of Natural Products against Acute and Chronic Inflammatory Diseases in the Oral Region

The oral inflammatory diseases are divided into two types: acute and chronic inflammatory diseases. In this review, we summarize the biological efficacy of herbal medicine, natural products, and their active ingredients against acute and chronic inflammatory diseases in the oral region, especially stomatitis and periodontitis. We review the effects of herbal medicines and a biscoclaurin alkaloid preparation, cepharamthin, as a therapy against stomatitis, an acute inflammatory disease. We also summarize the effects of herbal medicines and natural products against periodontitis, a chronic inflammatory disease, and one of its clinical conditions, alveolar bone resorption. Recent studies show that several herbal medicines such as kakkonto and ninjinto reduce LPS-induced PGE 2 production by human gingival fibroblasts. Among herbs constituting these herbal medicines, shokyo (Zingiberis Rhizoma) and kankyo (Zingiberis Processum Rhizoma) strongly reduce PGE 2 production. Moreover, anti-osteoclast activity has been observed in some natural products with anti-inflammatory effects used against rheumatoid arthritis such as carotenoids, flavonoids, limonoids, and polyphenols. These herbal medicines and natural products could be useful for treating oral inflammatory diseases

Protein kinase A enhances lipopolysaccharide-induced IL-6, IL-8, and PGE2 production by human gingival fibroblasts

<p>Abstract</p> <p>Objective</p> <p>Periodontal disease is accompanied by inflammation of the gingiva and destruction of periodontal tissues, leading to alveolar bone loss in severe clinical cases. Interleukin (IL)-6, IL-8, and the chemical mediator prostaglandin E₂(PGE₂) are known to play important roles in inflammatory responses and tissue degradation.</p> <p>Recently, we reported that the protein kinase A (PKA) inhibitor H-89 suppresses lipopolysaccharide (LPS)-induced IL-8 production by human gingival fibroblasts (HGFs). In the present study, the relevance of the PKA activity and two PKA-activating drugs, aminophylline and adrenaline, to LPS-induced inflammatory cytokines (IL-6 and IL-8) and PGE₂by HGFs were examined.</p> <p>Methods</p> <p>HGFs were treated with LPS from <it>Porphyromonas gingivalis </it>and H-89, the cAMP analog dibutyryl cyclic AMP (dbcAMP), aminophylline, or adrenaline. After 24 h, IL-6, IL-8, and PGE₂levels were evaluated by ELISA.</p> <p>Results</p> <p>H-89 did not affect LPS-induced IL-6 production, but suppressed IL-8 and PGE₂production. In contrast, dbcAMP significantly increased LPS-induced IL-6, IL-8, and PGE₂production. Up to 10 μg/ml of aminophylline did not affect LPS-induced IL-6, IL-8, or PGE₂production, but they were significantly increased at 100 μg/ml. Similarly, 0.01 μg/ml of adrenaline did not affect LPS-induced IL-6, IL-8, or PGE₂production, but they were significantly increased at concentrations of 0.1 and 1 μg/ml. In the absence of LPS, H-89, dbcAMP, aminophylline, and adrenaline had no relevance to IL-6, IL-8, or PGE₂production.</p> <p>Conclusion</p> <p>These results suggest that the PKA pathway, and also PKA-activating drugs, enhance LPS-induced IL-6, IL-8, and PGE₂production by HGFs. However, aminophylline may not have an effect on the production of these molecules at concentrations used in clinical settings (8 to 20 μg/ml in serum). These results suggest that aminophylline does not affect inflammatory responses in periodontal disease.</p

The effect of periodontal treatment for atherosclerotic indicator:cardio ankle vascular index(CAVI)

Independent from hyperlipidemia, hypertension, diabetes mellitus, smoking, a classical risk factor for arteriosclerosis, it has been shown that various types of chronic inflammationmay be involved in the development of arteriosclerosis. As a chronic inflammation, theprevalence rate of periodontal disease is reported to be about 80% at the age of 30 to 50years, and about ₉0% at the age of 60ʼs. In this study, cardio ankle vascular index (CAVI),a vascular function test, was measured as an indicator of arteriosclerosis before and aftertreatment of periodontal disease. As a result, it was revealed that CAVI statistically significantly decreased by treatment of periodontal disease. Further studies are needed in th

Comprehensive analysis including the nutritional point of view on the pathogenesis of periodontal disease

To clarify risk factors for periodontal disease from the viewpoints of physiology, blood biochemistry, and nutrition, a survey involving 364 persons (224 males, 140 females) who consulted the Medical Examination Center of Matsumoto Dental University Hospital was conducted. The pathogenesis of periodontal disease was investigated using the maximum Community Periodontal Index (CPI) and Attachment Loss (AL) values, and their distributions with respect to the sex were analyzed using Wilcoxonʼs rank sum test. Based on the CPI and AL values, the subjects were divided into 3 groups: healthy (0), mild (1–2), and severe (3–4). The mean values obtained from the physiological, dental, blood biochemical, and nutritional findings in the 3 groups were analyzed using the multiple comparison test. Furthermore, their distributions with respect to sex and smoking in the 3 groups were analyzed using Fisherʼs direct probability test. A p–value of 0.05 was regarded as significant. Factors influencing the CPI included the sex (male), body mass index (BMI), abdominal circumference, diastolic blood pressure, AL, alanine aminotransferase (ALT), fasting blood glucose, neutral fat, HDL cholesterol, and smoking. Factors influencing the AL included the sex (male), age, current number of teeth, CPI, lipid intake, manganese intake, vitamin C intake, monounsaturated fatty acid intake, polyunsaturated fatty acid intake, n–6 fatty acid intake, fruit intake, and smoking. The results suggest that the physiological, blood biochemical, and nutritional states are involved in the pathogenesis of periodontal disease. The CPI was associated with metabolic error in the presence of metabolic syndrome. There was an association between the AL and diet as an environmental factor