Effects of Cordyceps militaris supplementation on the immune response and upper respiratory infection in healthy adults: a randomized, double-blind, placebo-controlled study / 한국영양학회지

PURPOSE: Upper respiratory tract infections are major causes of the common cold throughout the world. Cordyceps militaris (C. militaris) is a well-known functional food for its anti-fatigue and immunomodulating activities. On the other hand, there are no reports on the protective effect against upper respiratory tract infections (URI). This study was a 12 week randomized, double-blind, and placebo-controlled trial in healthy volunteers. METHODS: A total of 100 subjects 20 ~ 70 years of age with a history of at least two colds in the year were enrolled in the study. The participants were required to record any adverse events and rate any cold-related incidents in a diary during the investigation period. The efficacy end point was the symptoms and incidence of URI, and changes in cytokines, IgA and natural killer (NK) cell activity. RESULTS: The Cordyceps militaris group over 12 weeks showed no significant impact on the incidence and symptomatology of URI compared to the placebo group. On the other hand, the experimental group showed significantly higher NK cell activity (p = 0.047) and IgA level (p = 0.035) compared to the placebo group. The NK-cell activity and IgA level were increased significantly by Cordyceps militaris over 12 weeks. CONCLUSION: The results suggest the possible beneficial immunomodulating effects, but the protective effects on URI could not be demonstrated under these conditions. Additional research will be needed to determine the efficacy and mechanisms of Cordyceps militaris function.

Effects of adherence to Korean diets on serum GGT and cardiovascular disease risk factors in patients with hypertension and diabetes / 한국영양학회지

PURPOSE: This study examined whether the supply of healthy Korean diets for 12 weeks is effective in improving the risk factors related to serum GGT and cardiovascular diseases in patients with hypertension and diabetes. METHODS: This study selected 41 patients, who were treated with hypertension and diabetes. The Korean diet was composed of cooked-rice, soup, kimchi, and various banchan with one serving called bapsang, which emphasize proportionally high consumption of vegetables and fermented foods, moderate to high consumption of legumes and fish, and low consumption of animal foods. The control group was instead instructed to “eat and exercise as usual” while following the Korean Diabetes Association's dietary guidelines with an intake that can assist in glycemic control, maintain adequate weight, and meet the nutritional requirements. The Korean diet group (21 patients) were served three healthy Korean meals a day for 12 weeks, and the control group (20 patients, who trained in the diet guideline of diabetes) maintained their usual diabetic diet. The serum GGT, blood pressure, heart rate, glycemic control data, cardiovascular risk indicators, and changes in diet measured at the four visits (week 0, 4, 8, and 12) during the course of 12 weeks were compared and evaluated. RESULTS: The serum GGT (p < 0.001), HbA1c (p = 0.004), heart rate (p = 0.007), weight (p = 0.002), Body Mass Index (p = 0.002), body fat mass (p < 0.001), body fat (%) (p < 0.001), and free fatty acid (p = 0.007) in the Korean diet group decreased significantly after the dietary intervention compared to the control group. The amount of intake of rice, whole grains, green vegetables, Kimchi, and soybean fermented food were increased significantly compared to the control group (p < 0.001). The Korean diet group showed significant decreases (p < 0.001) in the intake of animal protein, lipid, and cholesterol derived from animal foods compared to the control group but significant increases (p < 0.001) in the intake of total calories, folic acid, dietary fiber, sodium, potassium, and vitamins A, E, and C. CONCLUSION: In patients with hypertension and diabetes, it was confirmed that regular eating of a healthy Korean diet helps improve the risk factors for GGT and cardiovascular diseases.

Effects of Korean diet control nutrition education on cardiovascular disease risk factors in patients who underwent cardiovascular disease surgery / 한국영양학회지

PURPOSE: This study was conducted to verify the effects of increases in consuming Korean food in patients who underwent cardiovascular disease (CVD) surgery based on a Korean diet control education program and to investigate the effects of Korean diet control nutrition education on risk factors of CVD, changes in amounts of medication, and nutritional intakes. METHODS: The subjects consisted of 15 patients who have undergone CVD surgery within three years and continuously taken cardiovascular drugs. The Korean traditional diet (KTD) emphasizes intake of vegetables and fermented foods to lower saturated fat and cholesterol intake. We applied a KTD education program that included a modified DASH (The dietary approaches to stop hypertension) diet for cardiovascular disease patients. Korean diet control education was then applied to the patients for 12 weeks to evaluate the risk factors of CVD and the state of nutritional intakes. RESULTS: The Korean diet control compliance score increased significantly (p < 0.001) as Korean diet control education was implemented. Additionally, the obesity indexes, waist circumference (WC) (p = 0.002) and waist-to-hip ratio (WHR) decreased significantly (p < 0.001) after subjects received the education. Moreover, the glycemic control index, HbA1c, was significantly decreased (p < 0.05) from 7.3 ± 1.0% before the education to 7.0 ± 1.1% after the education. Changes in the amounts of Korean diet intake consisted of significant increases in cooked rice with whole grains, narmuls (vegetables either raw or cooked), kimchi, and traditional fermented foods following the education. Moreover, the nutritional intake after the education showed significant decreases (p < 0.05) in animal protein, animal lipids, and cholesterol. However, the intakes of Na, K, dietary fiber, vitamin A, vitamin B6, vitamin C, and folic acid were significantly increased. CONCLUSION: The active encouragement of consuming Korean food and the intervention of implementing diet control education positively affected nutritional intake, the obesity index and glycemic control of patients who have undergone CVD surgery.

In vitro Stimulation of NK Cells and Lymphocytes Using an Extract Prepared from Mycelial Culture of Ophiocordyceps sinensis

Ophiocordyceps sinensis is a natural fungus that has been valued as a health food and used in traditional Chinese medicine for centuries. The fungus is parasitic and colonizes insect larva. Naturally occurring O. sinensis thrives at high altitude in cold and grassy alpine meadows on the Himalayan mountain ranges. Wild Ophiocordyceps is becoming increasingly rare in its natural habitat, and its price limits its use in clinical practice. Therefore, the development of a standardized alternative is a great focus of research to allow the use of Ophiocordyceps as a medicine. To develop an alternative for wild Ophiocordyceps, a refined standardized extract, CBG-CS-2, was produced by artificial fermentation and extraction of the mycelial strain Paecilomyces hepiali CBG-CS-1, which originated from wild O. sinensis. In this study, we analyzed the in vitro immune-modulating effect of CBG-CS-2 on natural killer cells and B and T lymphocytes. CBG-CS-2 stimulated splenocyte proliferation and enhanced Th1-type cytokine expression in the mouse splenocytes. Importantly, in vitro CBG-CS-2 treatment enhanced the killing activity of the NK-92MI natural killer cell line. These results indicate that the mycelial culture extract prepared from Ophiocordyceps exhibits immune-modulating activity, as was observed in vivo and this suggests its possible use in the treatment of diseases caused by abnormal immune function.

A Case of Methanol Poisoning Treated with Continuous Renal Replacement Therapy: The Serial Measurements of Serum Methanol Concentrations in Methanol Poisoning

Methanol poisoning is a medical emergency that requires rapid elimination of the toxin and its metabolites for recovery. The danger of methanol results from the accumulation of its toxic metabolite formic acid. This accumulation may result in the development of metabolic acidosis, visual impairment, and damage to the basal ganglia. Extracorporeal treatment is recommended in severe cases of methanol poisoning with coma, seizure, new vision deficits, metabolic acidosis, high serum anion gap, elevated methanol concentrations or impaired kidney function. Although the serum methanol concentration is helpful in determining the use of extracorporeal treatment, methanol assays are not standard laboratory tests in Korea. Herein, we report a case of methanol poisoning in which the patient's clinical improvement was confirmed using serum and urine methanol levels.

Rooibos™: Automated schedule broadcast software for clinical pharmacology studies

Pharmacokinetic blood sampling is a prerequisite for successful early clinical trials. It is essential to take samples at the precise designated times to ensure the reliability of the clinical trial data; however, investigators have encountered difficulties in conducting procedures with limited manpower. We have recently developed automated schedule broadcast software (Rooibos™) to manage the precise scheduling of procedures for clinical trial centers. Rooibos™ is platform independent because it is programmed in the Java language. It generates scheduled times based on a reference time. It alarms at the scheduled times and pages subjects and alerts staff to prepare for the upcoming procedures. Rooibos™ can also group subjects when multiple clinical trials are conducted simultaneously in one or more clinical trial wards. This software may be applied to any study involving procedures that must be performed at designated times.

Development of a Korean Diet Score (KDS) and its application assessing adherence to Korean healthy diet based on the Korean Food Guide Wheels

The most critical point in the assessment of adherence to dietary guidelines is the development of a practical definition for adherence, such as a dietary pattern score. The purpose of this study was to develop the Korean Diet Score (KDS) based on the Korean Food Balance Wheel and to examine the association of KDS with various lifestyle characteristics and biochemical factors. The dietary data of 5,320 subjects from the 4th Korean National Health and Nutritional Examination Survey were used for the final analysis. The food guide was composed of six food group categories; 'grain dishes', 'fish and meat dishes', 'vegetable dishes', 'fruits', 'milk' and 'oils and sugars'. Based on the recommended serving numbers for each group, the scores measuring adherence to this food guide were calculated from the dietary information from the 24-hour dietary recall questionnaire, and then its correlation with various characteristics was assessed. KDS was significantly associated with several clinical, lifestyle and socioeconomic factors as well as diagnosed disease history. The higher quintile group of KDS showed a significantly lower level in fasting blood glucose, systolic blood pressure, triglycerides, current smoking and drinking as well as higher leisure time activity, house income and education. Furthermore, the KDS quintile group of women was inversely associated with hypertension, osteoporosis and diabetes. A higher KDS quintile was characterized with a higher intake of several critical nutrients, such as Ca, Fe and vitamins as well as a desirable nutrition balance such as the ratio of macronutrients. Our results demonstrate that KDS is a beneficial tool in assessing the adherence to a healthy diet based on the Korean dietary guidelines. We suggest that KDS could be a useful indicator for evaluating the dietary balance of the Korean population.

Gastrodia elata Blume and its pure compounds protect BV-2 microglial-derived cell lines against β-amyloid: The involvement of GRP78 and CHOP

Objectives: Gastrodia elata (GE) Blume (Orchidaceae) has been previously known for its therapeutic benefits against neurodegenerative diseases. Microglial activation and death have been implicated in the pathogenesis of a variety of neurodegenerative diseases, including Alzheimer's disease. In this study, GE and its pure components, gastrodin and 4-hydroxybenzyl alcohol (4HBA), were applied to β-amyloid-induced BV2 mouse microglial cells. Materials and Methods Cell viability was assessed by the MTT assay and Western blotting was also performed. Results: β-amyloid-induced cell death was shown to be induced time- and dose-dependently. To examine the cell death mechanism, we confirmed the involvement of ER stress signaling. C/EBP homologous protein (CHOP), a pro-apoptotic ER stress protein, was expressed at high levels but glucose-regulated protein 78 (GRP78), an anti-apoptotic ER stress protein with chaperone activity, was only slightly affected by treatment with β-amyloid. However, pretreatment with GE and its components inhibited the expression of CHOP but increased that of GRP78 in β-amyloid-treated cells. This study also showed that a single treatment with GE extracts, gastrodin, or 4HBA induced the expression of GRP78, a marker for enhanced protein folding machinery, suggesting a protective mechanism for GE against β-amyloid. Conclusions: This study reveals the protective effects of GE against β-amyloid-induced cell death, possibly through the enhancement of protein folding machinery of a representative protein, GRP78, and the regulation of CHOP in BV2 mouse microglial cells.

Preventive Effect of Korean Red Ginseng for Acute Respiratory Illness: A Randomized and Double-Blind Clinical Trial

Korean Red Ginseng (KRG) is a functional food and has been well known for keeping good health due to its anti-fatigue and immunomodulating activities. However, there is no data on Korean red ginseng for its preventive activity against acute respiratory illness (ARI). The study was conducted in a randomized, double-blinded, placebo-controlled trial in healthy volunteers (Clinical Trial Number: NCT01478009). Our primary efficacy end point was the number of ARI reported and secondary efficacy end point was severity of symptoms, number of symptoms, and duration of ARI. A total of 100 volunteers were enrolled in the study. Fewer subjects in the KRG group reported contracting at least 1 ARI than in the placebo group (12 [24.5%] vs 22 [44.9%], P = 0.034), the difference was statistically significant between the two groups. The symptom duration of the subjects who experienced the ARI, was similar between the two groups (KRG vs placebo; 5.2 +/- 2.3 vs 6.3 +/- 5.0, P = 0.475). The symptom scores were low tendency in KRG group (KRG vs placebo; 9.5 +/- 4.5 vs 17.6 +/- 23.1, P = 0.241). The study suggests that KRG may be effective in protecting subjects from contracting ARI, and may have the tendency to decrease the duration and scores of ARI symptoms.

Visceral fat and body weight are reduced in overweight adults by the supplementation of Doenjang, a fermented soybean paste

Various forms of fermented soybean products are well documented for their health benefits. The efficacy of anti-obesogenic effect of Doenjang, one of the most commonly used seasonings in Korean cuisine, has been reported only in animal models; thus, an evaluation of Doenjang needs to be conducted in human studies. We aimed to test the hypothesis that Doenjang supplementation reduces body weight and changes body composition in overweight adults. A total of 51 overweight adults participated in this study. A group of males with BMI > or = 23 kg/m2 and waist to hip ratio (WHR) > or = 0.90, and a group of females with BMI > or = 23 kg/m2 and WHR > or = 0.85 were randomly assigned to either a Doenjang supplement (9.9 g dry/day) group or a placebo group for a 12-week randomized, double-blind and placebo-controlled study. Anthropometric parameters, abdominal fat distribution by computerized tomography (CT) and blood components were measured before and after the intervention period. After the 12-week study, the Doenjang supplementation group had significant reductions in body weight (kg), body fat mass (kg) and body fat (%) compared to the placebo group, the supplementation of Doenjang resulted in a significant reduction in visceral fat (cm2), although no changes were observed in total and subcutaneous fat are as (cm2), serum lipid profiles and dietary intakes. The present study demonstrated that daily supplementation of 9.9 g dry/day of Doenjang for 12 weeks reduces body weight and visceral fat in overweight adults.

Effects of male silkworm pupa powder on the erectile dysfunction by chronic ethanol consumption in rats / 한국실험동물학회지

Erectile dysfunction (ED) is a highly prevalent disorder that affects millions of men worldwide. ED is now considered an early manifestation of atherosclerosis, and consequently, a precursor of systemic vascular disease. This study was designed to investigate the effects of male silkworm pupa powder (SWP) on the levels of nitric oxide synthase (NOS) expression, nitrite, and glutathione (GSH); lipid peroxidation; libido; and erectile response of the corpus cavernosum of the rat penis. We induced ED in the study animals by oral administration of 20% ethanol over 8 weeks. The SWP-treated male rats were divided into 3 groups that were orally administered 200, 400, and 800 mg/kg. The libido of the SWP-administered male rats was higher than that of the ethanol control group. In addition, the erectile response of the corpus cavernosum was restored in males on SWP administration, to a level similar to that of the normal group without ED. The testosterone concentration did not increase significantly. The lipid peroxidation in the corpus cavernosum of the male rats administered SWP decreased significantly. In contrast, compared to the ethanol group, SWP-administered male rats showed increased GSH levels in the corpus cavernosum. The level of nitrite and NOS expression in the corpus cavernosum of SWP-administered male rats increased significantly. These results indicated that SWP effectively restored ethanol-induced ED in male rats.

Anti-obesity and anti-diabetic effects of Yerba Mate (Ilex paraguariensis) in C57BL/6J mice fed a high-fat diet / 한국실험동물학회지

Yerba Mate, derived from the leaves of the tree, Ilex paraguariensis, is widely-used as a tea or as an ingredient in formulated foods. The aim of the present study was to evaluate the effects of Yerba Mate extract on weight loss, obesity-related biochemical parameters, and diabetes in high-fat diet-fed mice. To this end, by using in vivo animal models of dietary-induced obesity, we have made the interesting observations that Yerba Mate has the ability to decrease the differentiation of pre-adipocytes and to reduce the accumulation of lipids in adipocytes, both of which contribute to a lower growth rate of adipose tissue, lower body weight gain, and obesity. Our data from in vivo studies revealed that Yerba Mate treatment affects food intake, resulting in higher energy expenditure, likely as a result of higher basal metabolism in Yerba Mate-treated mice. Furthermore, in vivo effects of Yerba Mate on lipid metabolism included reductions in serum cholesterol, serum triglycerides, and glucose concentrations in mice that were fed a high fat diet. In conclusion, Yerba Mate can potentially be used to treat obesity and diabetes.

Actual Status of Constipation and Life Factors Affecting Constipation by Diagnosis of Rome in Female University Students in Korea

This study investigated the actual status of constipation. In total, 978 female students in Korea participated. We identified the relationship among constipation and life style, clothing patterns, housing patterns, dietary habits, and dietary intake in a constipation symptom group and a normal group. The actual constipation rate based on the Rome II criteria was 27.0% (n = 264). Body weight (p < 0.05) and body mass index (p < 0.05) in the constipation group were significantly higher than those in the normal group. The incidence of functional bowel disease and irritable bowel syndrome in the constipation group were significantly higher than those in the normal group. The discomfort of wearing underwear was significantly higher in the constipation group than that in the normal group. The constipation group revealed a significantly higher rate of irregular dietary habits than those in the normal group. The dietary diversity score of the normal group was 4.22 (p < 0.05), which was significantly higher than that of constipation group (4.12). No significant difference in life style factors was observed. It is necessary for university female students to correct their dietary habits, maintain food intake of three times per day, and select diverse foods. Furthermore, it is necessary for university female students to wear comfortable clothing to lessen symptoms and improve constipation rates.

Effects of Ficus carica paste on constipation induced by a high-protein feed and movement restriction in beagles / 한국실험동물학회지

Constipation is one of the most common functional digestive complaints worldwide. We investigated the laxative effects of figs (Ficus carica L) in a beagle model of constipation induced by high protein diet and movement restriction. The experiments were consecutively conducted over 9 weeks divided into 3 periods of 3 weeks each. All 15 beagles were subjected to a non-treatment (control) period, a constipation induction period, and a fig paste treatment period. We administered fig paste (12 g/kg daily, by gavage) for 3 weeks following a 3-week period of constipation induction in dogs. Segmental colonic transit time (CTT) was measured by counting radiopaque markers (Kolomark) using a radiograph performed every 6 h after feeding Kolomark capsules, until capsules were no longer observed. Fig paste significantly increased fecal quantity in constipated dogs, and segmental CTT was also reduced following fig paste administration. There were no significant differences in feed intake, water intake, body weight, or blood test results, between the constipation and fig paste administration periods. Our results demonstrate that fig is an effective treatment for constipation in beagles. Specifically, stool weight increased and segmental CTT decreased. Fig pastes may be useful as a complementary medicine in humans suffering from chronic constipation.

The Protective Effect of Epigallocatechin-3 Gallate on Ischemia/Reperfusion Injury in Isolated Rat Hearts: An ex vivo Approach

The aim of this study was to evaluate the preventive role of epigallocatechin-3 gallate (EGCG, a derivative of green tea) in ischemia/reperfusion (I/R) injury of isolated rat hearts. It has been suggested that EGCG has beneficial health effects, including prevention of cancer and heart disease, and it is also a potent antioxidant. Rat hearts were subjected to 20 min of normoxia, 20 min of zero-flow ischemia and then 50 min of reperfusion. EGCG was perfused 10 min before ischemia and during the whole reperfusion period. EGCG significantly increased left ventricular developed pressure (LVDP) and increased maximum positive and negative dP/dt (+/-dP/dtmax). EGCG also significantly increased the coronary flow (CF) at baseline before ischemia and at the onset of the reperfusion period. Moreover, EGCG decreased left ventricular end diastolic pressure (LVEDP). This study showed that lipid peroxydation was inhibited and Mn-SOD and catalase expressions were increased in the presence of EGCG. In addition, EGCG increased levels of Bcl-2, Mn-superoxide dismutase (SOD), and catalase expression and decreased levels of Bax and increased the ratio of Bcl-2/Bax in isolated rat hearts. Cleaved caspase-3 was decreased after EGCG treatment. EGCG markedly decreased the infarct size while attenuating the increase in lactate dehydrogenase (LDH) levels in the effluent. In summary, we suggest that EGCG has a protective effect on I/R-associated hemodynamic alteration and injury by acting as an antioxidant and anti-apoptotic agent in one.

The Correlation and Accuracy of Glucose Levels between Interstitial Fluid and Venous Plasma by Continuous Glucose Monitoring System / 당뇨병

BACKGROUND: Clinical experience with the continuous glucose monitoring systems (CGMS) is limited in Korea. The objective of this study is to evaluate the accuracy of the CGMS and the correlation between interstitial fluid and venous plasma glucose level in Korean healthy male subjects. METHODS: Thirty-two subjects were served with glucose solution contained same amount of test food's carbohydrate and test foods after separate overnight fasts. CGMS was performed over 3 days during hopitalization for each subjects. Venous plasma glucose measurements were carried out during 4 hours (0, 0.25, 0.5, 0.75, 1, 2, 4 hours) just before and after glucose solution and test food load. The performance of the CGMS was evaluated by comparing its readings to those obtained at the same time by the hexokinase method using the auto biochemistry machine (Hitachi 7600-110). Also, correlations between glucose recorded with CGMS and venous plasma glucose value were examined. RESULTS: CGMS slightly underestimated the glucose value as compared with the venous plasma glucose level (16.3 +/- 22.2 mg/dL). Correlation between CGMS and venous plasma glucose values throughout sensor lifetime is 0.73 (regression analysis: slope = 1.08, intercept = 8.38 mg/dL). Sensor sensitivity can deteriorate over time, with correlations between venous blood glucose and CGMS values dropping from 0.77 during 1st day to 0.65 during 2nd and 3rd day. CONCLUSION: The accuracy of data provided by CGMS may be less than expected. CGMS sensor sensitivity is decreased with the passage of time. But, from this study, CGMS can be used for glucose variability tendency monitoring conveniently to the Korean.

Functional Foods and Clinical Trial

There have been no specific health claims for functional foods. So, a lot of namely functional foods have been produced, and consumers confuse these functional foods with conventional foods. Last year, the Chonbuk National University Hospital established a clinical trial center for functional foods to meet the social needs for the validation of functional foods. For a successful clinical trial for functional foods, their characteristics should be understood. The followings should be considered before clinical trial: (1) The clinical trial for functional foods is different from that for pharmaceuticals, since the subjects for the functional foods should be healthy and sub-healthy persons, not patients. (2) Some clinical trials for functional foods should be done in a larger pool of subjects because functional foods show less significant effects compared to medical agents. (3) The diet should be more tightly regulated for clinical trial of functional foods. (4) Appropriate biomarkers are required for clinical trials for functional foods.

PDTC Inhibits TNF-alpha-Induced Apoptosis in MC3T3E1 Cells

Osteoblasts are affected by TNF-alpha overproduction by immune cells during inflammation. It has been suggested that functional NF-kappaB sites are involved in TNF-alpha-induced bone resorption. Thus, we explored the effect of pyrrolidine dithiocarbamate (PDTC), which potently blocks the activation of nuclear factor (NF-kappaB), on the induction of TNF-alpha-induced activation of JNK/SAPK, AP-1, cytochrome c, caspase and apoptosis in MC3T3E1 osteoblasts. Pretreatment of the cells with PDTC blocked TNF-alpha-induced NF-kappaB activation. TNF-alpha-induced activation of AP-1, another nuclear transcription factor, was suppressed by PDTC. The activation of c-Jun N-terminal kinase, implicated in the regulation of AP-1, was also down regulated by PDTC. TNF-alpha-induced apoptosis, release of cytochrome c and subsequent activation of caspase-3 were abolished by PDTC. TNF-alpha-induced apoptosis was partially blocked by Ac-DEVD-CHO, a caspase-3 inhibitor, suggesting that caspase-3 is involved in TNF-alpha- mediated signaling through NF-kappaB in MC3T3E1 osteoblasts. Thus, these results demonstrate that PDTC, has an inhibitory effect on TNF-alpha-mediated activation of JNK/SAPK, AP-1, cytochrome c release and subsequent caspase-3, leading to the inhibition of apoptosis. Our study may contribute to the treatment of TNF-alpha-associated immune and inflammatory diseases such as rheumatoid arthritis and periodontal diseases.

Salicylate Regulates Cyclooxygenase-2 Expression through ERK and Subsequent NF-kappaB Activation in Osteoblasts

The expression of cyclooxygenase-2 (COX-2) is a characteristic response to inflammation and can be inhibited with sodium salicylate. TNF-alpha plus IFN-gamma can induce extracellular signal-regulated kinase (ERK), IKK, IkappaB degradation and NF-kappaB activation. The inhibition of the ERK pathway with selective inhibitor, PD098059, blocked cytokine-induced COX-2 expression and PGE2 release. Salicylate treatment inhibited COX-2 expression induced by TNF-alpha/IFN-gamma and regulated the activation of ERK, IKK and I kappaB degradation and subsequent NF-kappaB activation in MC3T3E1 osteoblasts. Furthermore, antioxidants such as catalase, N-acetyl-cysteine or reduced glutathione attenuated COX-2 expression in combined cytokines-treated cells, and also inhibited the activation of ERK, IKK and NF-kappaB in MC3T3E1 osteoblasts. In addition, TNF-alpha/IFN-gamma stimulated ROS release in the osteoblasts. However, salicylate had no obvious effect on ROS release in DCFDA assay. The results showed that salicylate inhibited the activation of ERK and IKK, IkappaB degradation and NF-kappaB activation independent of ROS release and suggested that salicylate exerts its anti-inflammatory action in part through inhibition of ERK, IKK, IkappaB, NF-kappaB and resultant COX-2 expression pathway.

Blockade of p38 Mitogen-activated Protein Kinase Pathway Inhibits Interleukin-6 Release and Expression in Primary Neonatal Cardiomyocytes

The induction of interleukin-6 (IL-6) using combined proinflammatory agents (LPS/IFN-gamma or TNF-alpha/IFN-gamma) was studied in relation to p38 mitogen-activated protein kinase (MAPK) and NF-kappaB transcriptional factor in primary neonatal cardiomyocytes. When added to cultures of cardiomyocytes, the combined agents (LPS/IFN-gamma or TNF-alpha/IFN-gamma) had stimulatory effect on the production of IL-6 and the elevation was significantly reduced by SB203580, a specific p38 MAPK inhibitor. SB203580 inhibited protein production and gene expression of IL-6 in a concentration-dependent manner. In this study, IFN-gamma enhancement of TNF-alpha-induced NF-kappaB binding affinity as well as p38 MAP kinase activation was observed. However, a specific inhibitor of p38 MAPK, SB203580, had no effect on TNF-alpha/IFN-gamma or LPS/IFN-gamma-induced NF-kappaB activation. This study strongly suggests that these pathways about TNF-alpha/IFN-gamma or LPS/IFN-gamma-activated IL-6 release can be primarily dissociated in primary neonatal cardiomyocytes.