Effect of maternal age at childbirth on insulin resistance: the 2010 Korean National Health and Nutrition Examination Survey.

OBJECTIVE: This study aimed to assess insulin resistance according to maternal age at childbirth. PATIENTS AND METHODS: The data used in this study were obtained from the 2010 Korean National Health and Nutrition Examination Survey. This study included a total of 2233 nondiabetic female subjects ≥30 years of age that were subdivided into groups according to their obesity and abdominal obesity (AOB) statuses. The homoeostasis model assessment of insulin resistance (HOMA-IR) was used to quantify the insulin resistance according to age at first childbirth and last childbirth. RESULTS: Age at first childbirth showed a negative relationship with HOMA-IR in both the nonobese and non-AOB groups, while age at last childbirth showed a positive relationship with HOMA-IR in both the nonobese and non-AOB groups. A multivariate logistic regression analysis revealed that ages at first and last childbirth were significantly associated with the highest HOMA-IR quartile. The odds ratio was 0·9 (95% confidence interval: 0·82-0·98) for age at first childbirth, and 1·07 (95% confidence interval: 1·01-1·14) for age at last childbirth in the nonobese and non-AOB groups. CONCLUSION: In conclusion, this study suggests that insulin resistance is increased in females who experienced their first childbirth at a younger age or their last childbirth at a later age, particularly in nonobese individuals. Because these data suggest that childbearing age could be an independent risk factor for diabetes, a high-quality prospective study assessing the relationship between childbearing age and insulin resistance should be performed.

Isoliquiritigenin isolated from the roots of Glycyrrhiza uralensis inhibits LPS-induced iNOS and COX-2 expression via the attenuation of NF-kappaB in RAW 264.7 macrophages.

In this study, the anti-inflammatory effects of flavonoids isolated from the roots of Glycyrrhiza uralensis (Leguminosae), namely, isoliquiritin (the glycoside of isoliquirigenin) and isoliquiritigenin (the aglycone of isoliquiritin) were evaluated on lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. Isoliquiritigenin (ILG) more potently inhibited LPS-induced nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production than isoliquiritin (ILT). Consistent with these findings, ILG reduced the LPS-induced expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the protein and mRNA levels in a concentration-dependent manner, as determined by Western blotting and RT-PCR, respectively. In addition, the release of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), and the mRNA expression levels of these cytokines were reduced by ILG in a dose-dependent manner. Moreover, ILG attenuated the LPS-induced DNA binding activity and the transcription activity of nuclear factor-kappa B (NF-kappaB), and this was associated with a decrease in inhibitory kappa B-alpha (IkappaB-alpha) phosphorylation and in the subsequent blocking of p65 and p50 protein translocations to the nucleus. Furthermore, ILG suppressed the phosphorylations of IkappaB kinase (IKK), ERK1/2, and p38, whereas the phosphorylation of JNK1/2 was unaffected. These results suggest that the anti-inflammatory properties of ILG are caused by iNOS, COX-2, TNF-alpha, and IL-6 down-regulation due to NF-kappaB inhibition via the suppression of IKK, ERK1/2 and p38 phosphorylation in RAW 264.7 cells.

Inhibition of LPS-induced NO and PGE2 production by asiatic acid via NF-kappa B inactivation in RAW 264.7 macrophages: possible involvement of the IKK and MAPK pathways.

In the present study, we investigated the effect of asiatic acid (the aglycon of asiaticoside) and asiaticoside isolated from the leaves of Centella asiatica (Umbelliferae) on LPS-induced NO and PGE(2) production in RAW 264.7 macrophage cells. Asiatic acid more potently inhibited LPS-induced NO and PGE(2) production than asiaticoside. Consistent with these observations, the protein and mRNA expression levels of inducible iNOS and COX-2 enzymes were inhibited by asiatic acid in a concentration-dependent manner. In addition, asiatic acid dose-dependently reduced the production of IL-6, IL-1 beta and TNF-alpha in LPS-stimulated RAW 264.7 macrophage cells. Furthermore, asiatic acid inhibited the NF-kappaB activation induced by LPS, and this was associated with the abrogation of I kappa B-alpha degradation and with subsequent decreases in nuclear p65 and p50 protein levels. Moreover, the phosphorylations of IKK, p38, ERK1/2, and JNK in LPS-stimulated RAW 264.7 cells were suppressed by asiatic acid in a dose-dependent manner. These results suggest that the anti-inflammatory properties of asiatic acid might be the results from the inhibition of iNOS, COX-2, IL-6, IL-1 beta, and TNF-alpha expressions through the down-regulation of NF-kappaB activation via suppression of IKK and MAP kinase (p38, ERK1/2, and JNK) phosphorylation in RAW 264.7 cells.

Anti-inflammatory effect of buddlejasaponin IV through the inhibition of iNOS and COX-2 expression in RAW 264.7 macrophages via the NF-kappaB inactivation.

Buddlejasaponin IV isolated from Pleurospermum kamtschatidum is an anti-inflammatory compound that inhibits NO, PGE(2) and TNF-alpha production. Here, we studied the mode of action of this compound. Buddlejasaponin IV (2.5-10 microM) reduced lipopolysaccaride (LPS (1 microg ml(-1)))-induced levels of iNOS and COX-2 at the protein levels, and iNOS, COX-2, TNF-alpha, interleukin (IL)-1beta and IL-6 mRNA expression in RAW 264.7 macrophages in a concentration-dependent manner, as determined by Western blotting and RT-PCR, respectively. Buddlejasaponin IV inhibited the LPS-induced activation of nuclear factor-kappaB (NF-kappaB), a transcription factor necessary for proinflammatory mediators, iNOS, COX-2, TNF-alpha, IL-1beta and IL-6 expression. This effect was accompanied by a parallel reduction in IkappaB-alpha degradation and phosphorylation, and by the nuclear translocation of the NF-kappaB p65 subunit. The effects of buddlejasaponin IV on acute phase inflammation were studied on serotonin- and carrageenan-induced paw edema. The antiedematous effect of buddlejasaponin IV was compared with 10 mg kg(-1) of indomethacin p.o. Maximum inhibitions of 26 and 41% were noted at a dose of 20 mg kg(-1) for serotonin- and carrageenan-induced paw edema, respectively. The analgesic effect of buddlejasaponin IV was evaluated using acetic acid-induced writhing and hot-plate tests. Buddlejasaponin IV (10 and 20 mg kg(-1), p.o.) was found to have a marked analgesic effect in both models. These results suggest that the inhibitions of the expressions of iNOS, COX-2, TNF-alpha, IL-1beta and IL-6 by blocking NF-kappaB activation, are responsible for the anti-inflammatory effects of buddlejasaponin IV isolated from P. kamtschatidum.

Discordance in the levels of hemoglobin A1C and glycated albumin: Calculation of the glycation gap based on glycated albumin level.

OBJECTIVE: The glycation gap (G-gap) is an empirical measure of the extent of the difference between HbA1C and fructosamine levels. Several studies have shown that the presence of a G-gap is linked to diabetic nephropathy, but possible artifacts caused by dependence of the fructosamine level on the extent of serum protein metabolism require careful consideration. We investigated the consistency of G-gaps measured by assaying glycated albumin (GA) levels to identify factors associated with G-gap variations. METHOD: A total of 457 pairs of observations, like an HbA1c and GA measurement at the same clinic visit, were obtained from 170 Korean patients with type 2 diabetes. HbA1c and GA levels were measured simultaneously in two or three separate occasions. Each G-gap was calculated as the difference between the measured HbA1c level and that predicted by the GA level. All patients underwent abdominal computed tomography, and the areas of subcutaneous and visceral fat were measured. RESULTS: The G-gaps were all significantly inter-correlated over time (γ=0.755, P<0.001).The direction of each G-gap was consistent. The body mass index (BMI), visceral fat area, and the estimated glomerular filtration rate (eGFR) increased linearly from the lowest to the highest G-gap quartile (all P values <0.05). Upon multivariate analysis, both visceral fat area and the eGFR were significantly associated with a G-gap. CONCLUSIONS: A G-gap determined using GA measurements is consistent within an individual over time. The G-gap is associated with visceral fat and kidney function in patients with type 2 diabetes.

Insulin Resistance Distribution and Cut-Off Value in Koreans from the 2008-2010 Korean National Health and Nutrition Examination Survey.

BACKGROUND: We sought to identify the distribution and cut-off value of the 'homeostasis model assessment of insulin resistance' (HOMA-IR) according to gender and menopausal status for metabolic syndrome in Koreans. METHODS: Data were from the Korean National Health and Nutrition Examination Survey in 2008-2010. The subjects included adults aged 20 years or older. We excluded participants who had diabetes or fasting serum glucose ≥ 7 mmol/L. Finally, 11,121 subjects (4,911 men, 3,597 premenopausal women, 2,613 postmenopausal women) were enrolled. The modified Adult Treatment Panel III criteria were used to define metabolic syndrome. RESULTS: The mean HOMA-IR was 2.11 (2.07-2.15) for men, 2.0 (1.97-2.04) for premenopausal women, and 2.14 (2.2-2.19) for postmenopausal women. The first cut-off values in men, premenopausal women, and postmenopausal women were 2.23 (sensitivity 70.6%, specificity 66.9%), 2.39 (sensitivity 72.3%, specificity 76.4%), and 2.48 (sensitivity 51.9%, specificity 80.2%), respectively. Based on the first HOMA-IR cut-off value, the prevalence of metabolic syndrome was 22.9% in men, 13.7% in premenopausal women, and 51.6% in postmenopausal women. The second cut-off value was around 3.2 in all three groups. Based on the second HOMA-IR cut-off value, the prevalence of metabolic syndrome was 50.8% in men, 42.5% in premenopausal women, and 71.6% in postmenopausal women. CONCLUSION: In conclusion, the first cut-off values for HOMA-IR were 2.2-2.5 and the second cut-off value was 3.2 in Korea. The distribution of HOMA-IR showed differences according to gender and menopausal status. When we apply HOMA-IR, we should consider gender, menopausal status, and the prevalence of metabolic syndrome.

Risk Factors for the Development and Progression of Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus and Advanced Diabetic Retinopathy.

BACKGROUND: Some patients with type 2 diabetes mellitus (T2DM) do not develop diabetic kidney disease (DKD) despite the presence of advanced diabetic retinopathy (DR). We aimed to investigate the presence of DKD and its risk factors in patients with T2DM and advanced DR. METHODS: We conducted a cross-sectional study in 317 patients with T2DM and advanced DR. The phenotypes of DKD were divided into three groups according to the urine albumin/creatinine ratio (uACR, mg/g) and estimated glomerular filtration rate (eGFR, mL/min/1.73 m²): no DKD (uACR <30 and eGFR ≥60), non-severe DKD (uACR ≥30 or eGFR <60), and severe DKD (uACR ≥30 and eGFR <60). Mean systolic and diastolic blood pressure, mean glycosylated hemoglobin (HbA1c) level, and HbA1c variability (standard deviation [SD] of serial HbA1c values or HbA1c-SD) were calculated for the preceding 2 years. RESULTS: The prevalence of no DKD, non-severe DKD, and severe DKD was 37.2% (n=118), 37.0% (n=117), and 25.8% (n=82), respectively. HbA1c-SD and the triglyceride/high density lipoprotein cholesterol (TG/HDL-C) ratio correlated positively with uACR and negatively with eGFR. Multiple linear regression analyses showed that the HbA1c-SD and TG/HDL-C ratio were significantly related with eGFR. Multiple logistic regression analyses after adjusting for several risk factors showed that HbA1c-SD and the TG/HDL-C ratio were significant risk factors for severe DKD. CONCLUSION: The prevalence of DKD was about 60% in patients with T2DM and advanced DR. HbA1c variability and TG/HDL-C ratio may affect the development and progression of DKD in these patients.

Current research and future directions in pattern identification: Results of an international symposium.

A symposium on pattern identification (PI) was held at the Korea Institute of Oriental Medicine (KIOM) on October 2, 2013, in Daejeon, South Korea. This symposium was convened to provide information on the current research in PI as well as suggest future research directions. The participants discussed the nature of PI, possible research questions, strategies and future international collaborations in pattern research. With eight presentations and an extensive panel discussion, the symposium allowed participants to discuss research methods in traditional medicine for PI. One speaker presented the topic, 'Clinical pattern differentiation and contemporary research in PI.' Two speakers presented current trends in research on blood stasis while the remaining five other delegates discussed the research methods and future directions of PI research. The participants engaged in in-depth discussions regarding the nature of PI, potential research questions, strategies and future international collaborations in pattern research.

Korean studies on blood stasis: an overview.

Blood stasis is one of the important pathological concepts in Korean medicine. We analyzed the Korean studies concerning blood stasis. We searched for articles in eight electronic databases from their inception to September, 2014. We included reviews, clinical studies, and preclinical studies that had studied blood stasis and excluded articles in which blood stasis was not mentioned or in which the original authors had not explained blood stasis. Of 211 total included studies, 19 were reviews, 52 were clinical studies, and 140 were preclinical articles. "Stagnant blood within the body" was the most frequently mentioned phrase of the traditional concept of blood stasis. Traumatic injury was the most frequently studied disease/condition in the clinical studies. In the preclinical studies, coagulopathy was studied most frequently, followed by hyperviscosity, hyperlipidemia, inflammation, neoplasm, ischemic brain injury, and atherosclerosis. Hyeolbuchukeo-tang and Angelicae Gigantis Radix were the most frequent formula and single herb, respectively, used in the blood stasis researches. The results showed that blood stasis was mainly recognized as disorder of circulation and many studies showed the effectiveness of activating blood circulating herbs for diseases and pathologies such as traumatic injury or coagulopathy. Further studies are needed in the pathologic mechanisms and various diseases of blood stasis.

A Retrospective Analysis of Patients' Conditions Using Acupuncture in a Traditional Korean Medicine Hospital.

Objective. The aim of this study was to identify the patient demographics, health issues, and type of acupuncture treatments who visited a traditional Korean medical hospital for acupuncture treatment. Methods. We retrospectively analysed the data using the electronic medical records (EMRs) of patients treated with at least one treatment of acupuncture from 1 January 2010 to December 2012 in the Chung-Ju Korean hospital at Semyung University. Results. The total number of identified patients was 1189 inpatients and 10138 outpatients. The 50-59 age group received acupuncture treatment in the hospital the most, followed by the 40-49 age group. Among the patients undergoing acupuncture treatment because of a diagnosis of pain, 82.74% were outpatients and 72.85% were inpatients. Additionally, all patients with a spine condition received acupuncture treatment. The most common musculoskeletal conditions of patients at the traditional Korean medicine (TKM) hospital were associated with spine conditions, such as low back pain and neck pain. Various treatments have been performed at the hospital in conjunction with acupuncture. The study results show a high prevalence of acupuncture treatment for diagnosed diseases. Conclusion. Our study suggests the need to investigate additional TKM hospitals to analyse characteristics of patients who received specific treatments. Analysis of the characteristics of patients treated with Korean acupuncture at the TKM hospital in this study will help future researchers who want to implement strong clinical evidence. However, we cannot completely discount all symptoms because of the retrospective nature of this study, and only one hospital was used, which limits the generalisation of our findings.

The effects of thyrotropin-suppressing therapy on bone metabolism in patients with well-differentiated thyroid carcinoma.

Studies on the effects of levothyroxine (LT4) therapy on bone and bone metabolism have yielded conflicting results. This 1-year prospective study examined whether LT4 in patients with well-differentiated thyroid carcinoma (DTC) is a risk factor for bone mass loss and the subsequent development of osteoporosis. We examined 93 patients with DTC over 12months after initiating LT4 therapy (early postoperative period). We examined another 33 patients on long-term LT4 therapy for DTC (late postoperative period). Dual energy X-ray absorptiometry was performed at baseline and after 1year. The mean bone losses during the early postoperative period in the lumbar spine, femoral neck, and total hip, calculated as the percentage change between levels at baseline and 12months, were -0.88, -1.3 and -0.81%, respectively. Bone loss was more evident in postmenopausal women (lumbar spine -2.1%, femoral neck -2.2%, and hip -2.1%; all P<0.05). We compared the changes in annual bone mineral density (BMD) in postmenopausal women according to calcium/vitamin D supplementation. Bone loss tended to be higher in the postmenopausal women receiving no supplementation. There was no decrease in BMD among patients during the late postoperative period. The mean bone loss was generally greater in the early than in the late postoperative group, and this was significant at the lumbar spine (P=0.041) and femoral neck (P=0.010). TSH-suppressive levothyroxine therapy accelerates bone loss, predominantly in postmenopausal women and exclusively during the early post-thyroidectomy period.

Herbal medicine (Gan Mai Da Zao decoction) for depression: a systematic review and meta-analysis of randomized controlled trials.

The objective of this review was to analyze the trial data on the efficacy and safety of Gan Mai Da Zao (GMDZ) decoction for depression. PubMed, the Cochrane Library, and EMBASE, AMED, Korea Med, DBPIA, OASIS, RISS, KISS, CNKI, Wan Fang Database, and VIP were searched through to May 2014. Randomized controlled trials (RCTs) testing GMDZ decoction for any type of depression were considered. All RCTs of GMDZ decoction or modified GMDZ decoction were included. Data were extracted by 2 independent reviewers. Meta-analysis was used for the pooled data. A total of 298 potentially relevant studies were identified, and 13 RCTs met our inclusion criteria. All of the included RCTs had a high risk of bias across their domains. Three RCTs failed to show favorable effects of GMDZ decoction on response rate or HAMD score in major depression. One RCT showed a beneficial effect of GMDZ decoction on response rate in post-surgical depression, while another failed to do so. Two studies showed favorable effects on response rate in post-stroke depression, while another two failed to do so. A meta-analysis, however, showed that GMDZ decoction produced better response rates than anti-depressants in post-stroke depression (RR: 1.17, I(2)=15%). One trial failed to show any beneficial effects of GMDZ decoction on response rate or HAMD score in depression in an elderly sample. Two trials tested GMDZ decoction in combination with anti-depressants but failed to show effects on response rate in major depression, while another did show beneficial effects on response rate in post-stroke depression. In summary, our systematic review and meta-analysis failed to provide evidence of the superiority of GMDZ decoction over anti-depressant therapies for major depression, post-surgical depression, or depression in the elderly, although there was evidence of an effect in post-stroke depression. The quality of evidence for this finding was low, however, because of a high risk of bias.

Accelerated disease progression after discontinuation of sorafenib in a patient with metastatic papillary thyroid cancer.

Distant metastases from papillary thyroid carcinoma (PTC) are rare and are associated with a poor prognosis. Here, we describe a patient with metastatic PTC who was treated with a tyrosine kinase inhibitor (TKI, sorafenib) for several months that was acutely exacerbated by discontinuation. A 43-year-old male was diagnosed with PTC in February 2004 and underwent total thyroidectomy followed by two courses of high-dose radioactive iodine (RAI) therapy. Despite two additional courses of high-dose RAI therapy, lung and muscle metastases were developed. Treatment with sorafenib was begun in September 2010. After 11 months treatment of sorafenib, newly developed metastatic lesions were found in mediastinal lymph nodes, liver, and bones. Considered as treatment failure, the administration of sorafenib was discontinued. Two weeks after sorafenib treatment was stopped, the disease progressed abruptly and caused death of the patient by respiratory failure. In our patient, PTC progressed rapidly after the cessation of sorafenib treatment. Patients with several other types of cancer have also experienced such rapid disease progression, termed "flare-ups." Physicians should be aware that flare-ups may occur in advanced PTC patients following the cessation of TKI therapy.

Herbal medicine (Gan Mai Da Zao decoction) for depression: a systematic review protocol.

INTRODUCTION: The aim of this systematic review is to analyse trial data on the effectiveness of a herbal medicine (Gan Mai Da Zao (GMDZ) decoction) in treating depression. METHODS AND ANALYSIS: 12 databases will be searched from their inception: PubMed, EMBASE, AMED, the Cochrane Library, five Korean medical databases (KoreaMed, DBpia, OASIS, the Research Information Service System (RISS) and the Korean Studies Information Service System (KISS)) and three Chinese medical databases (China National Knowledge Infrastructure (CNKI), the Wanfang Database and the Chinese Scientific Journals Database (VIP)). Randomised clinical trials (RCTs) or quasi-RCTs using a GMDZ decoction for any type of depression will be considered. The selection of the studies, data abstraction and validations will be performed independently by two researchers. DISSEMINATION: The findings will be disseminated to appropriate audiences via peer-reviewed publication and conference presentations. TRIAL REGISTRATION NUMBER: PROSPERO 2013:CRD42013005100.

Conceptualization and utilization of blood stasis syndrome among doctors of Korean medicine: results of a web-based survey.

This survey aimed to assess the conceptualization of and utilization of blood stasis syndrome within traditional East Asian medicine among Doctors of Korean Medicine (DKMs). A survey was conducted with 22 questions classified into four categories (the present status, problems and requirements of a BSS diagnosis; the concept, diseases and prescriptions regarding BSS; the present status and problems with the Korean standard classification of diseases (KCD) relevant to BSS and the demographic characteristics of the survey respondents). A total of 17,550 DKMs affiliated with the association of Korean medicine were sent surveys via e-mail. Of the 678 respondents, more than half (53%) had difficulties with the diagnosis of BSS because objective measurement methods were not readily available. Most respondents (88%) thought that the development of an objective diagnostic method for BSS was necessary. Regarding the concept of blood stasis, "an abnormal mass in organ and tissue" considered the most significant indicator, followed by extravasated blood, the blood circulating sluggishly and a disorder of the blood cells. According to 606 DKMs, a traumatic injury was the most frequent reason for BSS in the clinic. And the Dangkwisoo-san was most frequently mentioned prescription for BSS in the clinic. The majority of respondents (76%) reported that it was necessary for an additional code of BSS in KCD. Our data suggest the need to develop more objective diagnostic tools for BSS diagnosis. Future research into BSS should consider DKMs' perceptions of BSS, diseases relevant to BSS and KCD codes. However, we cannot completely discount the possibility that the low response rate could indicate a biased selection of respondents and limit the interpretations of our study results.

Bee venom acupuncture for rheumatoid arthritis: a systematic review protocol.

INTRODUCTION: This systematic review aims to analyse the trial data on the effects of bee venom acupuncture (BVA) for rheumatoid arthritis (RA). METHODS AND ANALYSIS: The following 14 databases will be searched from their inception to March 2014: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), AMED, CINAHL, six Korean medical databases (OASIS, Korean Traditional Knowledge Portal, Korean Studies Information Service System, KoreaMed, Korean Medical Database and DBPIA) and three Chinese databases including CNKI (China National Knowledge Infrastructure), Wanfang and VIP. The methodological quality will be assessed using the Cochrane risk of bias tool. DISSEMINATION: The systematic review will be published in a peer-reviewed journal. The review will also be disseminated electronically and in print. TRIAL REGISTRATION NUMBER: PROSPERO 2013: CRD42013005853.

Monotropein isolated from the roots of Morinda officinalis ameliorates proinflammatory mediators in RAW 264.7 macrophages and dextran sulfate sodium (DSS)-induced colitis via NF-κB inactivation.

We previously demonstrated that monotropein isolated from the roots of Morinda officinalis (Rubiaceae) has anti-inflammatory effects in vivo. In the present study, we investigated the molecular mechanisms underlying the anti-inflammatory effects of monotropein in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages and dextran sulfate sodium (DSS)-induced colitis mouse model. Monotropein was found to inhibit the expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) mRNA in LPS-induced RAW 264.7 macrophages. Treatment with monotropein decreased the DNA binding activity of nuclear factor-κB (NF-κB). Consistent with these findings, monotropein also suppressed phosphorylation and degradation of inhibitory κB-α (IκB-α), and consequently the translocations of NF-κB. In the DSS-induced colitis model, monotropein reduced disease activity index (DAI), myeloperoxidase (MPO) activity, and inflammation-related protein expressions by suppressing NF-κB activation in colon mucosa. Taken together, these findings suggest that the anti-inflammatory effects of monotropein are mainly related to the inhibition of the expressions of inflammatory mediators via NF-κB inactivation, and support its possible therapeutic role in colitis.

Quaternary alkaloid, pseudocoptisine isolated from tubers of Corydalis turtschaninovi inhibits LPS-induced nitric oxide, PGE(2), and pro-inflammatory cytokines production via the down-regulation of NF-kappaB in RAW 264.7 murine macrophage cells.

It is well known that pro-inflammatory mediators like nitric oxide (NO), prostaglandin E(2) (PGE(2)), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) contribute to the courses of many inflammatory diseases. In the present study, the authors investigated the anti-inflammatory effects of pseudocoptisine, a quaternary alkaloid with a benzylisoquinoline skeleton, which was isolated from the tubers of Corydalis turtschaninovii by examining its inhibitory effects on pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated murine macrophage RAW 264.7 cells. Pseudocoptisine caused dose-dependent reductions in the levels of inducible nitric oxide (iNOS) and cyclooxygenase-2 (COX-2) at both protein and mRNA levels and concomitant decreases in PGE(2) and NO production. In addition, it was found that pseudocoptisine suppressed the production and mRNA expressions of inflammatory cytokines, such as, TNF-alpha and IL-6. Furthermore, molecular data revealed that pseudocoptisine inhibited the LPS-stimulated DNA binding activity and the transcription activity of nuclear factor-kappa B (NF-kappaB). Moreover, this effect was accompanied by decreases in the phosphorylation of inhibitory kappaB (IkappaB)-alpha and in the subsequent blocking of p65 subunit of NF-kappaB translocation to the nucleus. In addition, pseudocoptisine dose-dependently inhibited the phosphorylations of ERK and p38. Taken together, these results suggest that pseudocoptisine reduces levels of the pro-inflammatory mediators, such as, iNOS, COX-2, TNF-alpha, and IL-6 through the inhibition of NF-kappaB activation via the suppression of ERK and p38 phosphorylation in RAW 264.7 cells. These findings reveal in part the molecular basis for the anti-inflammatory properties of pseudocoptisine.