Melanogenesis-inducing effect of cirsimaritin through increases in microphthalmia-associated transcription factor and tyrosinase expression.

The melanin-inducing properties of cirsimaritin were investigated in murine B16F10 cells. Cirsimaritin is an active flavone with methoxy groups, which is isolated from the branches of Lithocarpus dealbatus. Tyrosinase activity and melanin content in murine B16F10 melanoma cells were increased by cirsimaritin in a dose-dependent manner. Western blot analysis revealed that tyrosinase, tyrosinase-related protein (TRP) 1, TRP2 protein levels were enhanced after treatment with cirsimaritin for 48 h. Cirsimaritin also upregulated the expression of microphthalmia-associated transcription factor (MITF) after 24 h of treatment. Furthermore, cirsimaritin induced phosphorylation of cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) in a dose-dependent manner after treatment for 15 min. The cirsimaritin-mediated increase of tyrosinase activity was significantly attenuated by H89, a cAMP-dependent protein kinase A inhibitor. These findings indicate that cirsimaritin stimulates melanogenesis in B16F10 cells by activation of CREB as well as upregulation of MITF and tyrosinase expression, which was activated by cAMP signaling. Finally, the melanogenic effect of cirsimaritin was confirmed in human epidermal melanocytes. These results support the putative application of cirsimaritin in ultraviolet photoprotection and hair coloration treatments.

Aralia cordata inhibits triacylglycerol biosynthesis in HepG2 cells.

Glycerol-3-phosphate acyltransferase (GPAT) catalyzes the first committed step in triacylglycerol (TAG) and phospholipid biosynthesis, and has been considered as one of the drug targets for treating hepatic steatosis, insulin resistance, and other metabolic disorders. The aim of this study was to investigate the GPAT inhibitors from natural products and to evaluate their effects. The methanol extract of Aralia cordata roots showed a strong inhibitory effect on the human GPAT1 activity. A further bioactivity-guided approach led to the isolation of ent-pimara-8(14),15-dien-19-oic acid, (PA), one of the major compounds of A. cordata, which suppressed the GPAT1 activity with IC50 value of 60.5 µM. PA markedly reduced de novo lysophosphatidic acid synthesis through inhibition of GPAT activity and therefore significantly decreased synthesis of TAG in the HepG2 cells. These results suggest that PA as well as A. cordata root extract could be beneficial in controlling lipid metabolism.

2″,4″-O-diacetylquercitrin, a novel advanced glycation end-product formation and aldose reductase inhibitor from Melastoma sanguineum.

A new flavonoid, 2,″4″-O-diacetylquercitrin (1), along with six known flavonoids (2-7) were isolated from the aerial parts of Melastoma sanguineum. The structure of the new flavonoid was established by extensive spectroscopic studies and chemical evidence. The inhibitory effects of isolated compounds (1-7) on advanced glycation end-products (AGEs) formation and rat lens aldose reductase (RLAR) in vitro were examined. Of the tested compounds, compound 1 was the strongest inhibitor of AGEs, with an IC50 of 11.46±0.44 µm. In the RLAR assay, all tested compounds exhibited greater inhibitory effects on RLAR than that of a positive control, 3,3-tetramethyleneglutaric acid (IC50=28.8±1.5 µm); compound 1 exhibited the strongest RLAR-inhibitory activity, with an IC50 of 0.077±0.003 µm.

The Korean prediction model for adolescents' future smoking intentions.

OBJECTIVES: The purpose of this study was to develop a prediction model for future smoking intention among Korean adolescents aged 13 to 15 in order to identify the high risk group exposed to future smoking. METHODS: The data was collected from a total of 5940 students who participated in a self-administrated questionnaire of a cross-sectional school-based survey, the 2004 Korea Global Youth Tobacco Survey. Chi-square tests and logistic regression analyses were carried out to identify the relevant determinants associated with intentions of adolescents' future smoking. Receiver Operation Characteristic (ROC) assessment was applied to evaluate the explanation level of the developed prediction model. RESULTS: 8.4% of male and 7.2% of female participants show their intentions of future smoking. Among non-smoking adolescents; who have past smoking experience [odds ratio (OR) 2.73; 95% confidence interval (CI) 1.92 - 3.88]; who have intentions of smoking when close friends offer a cigarette (OR 31.47; 95% CI = 21.50 - 46.05); and who have friends that are mostly smokers (OR 5.27; 95% CI = 2.85 - 9.74) are more likely to be smokers in the future. The prediction model developed from this study consists of five determinants; past smoking experience; parents smoking status; friends smoking status; ownership of a product with a cigarette brand logo; and intentions of smoking from close friends' cigarette offer. The area under the ROC curve was 0.8744 (95% CI=0.85 - 0.90) for current non-smokers. CONCLUSIONS: For efficiency, school-based smoking prevention programs need to be designed to target the high risk group exposed to future smoking through the prediction model developed by the study, instead of implementing the programs for all the students.

Sesquiterpenoids isolated from the flower buds of Tussilago farfara L. inhibit diacylglycerol acyltransferase.

Inhibition of acyl CoA:diacylglycerol acyltransferase (DGAT), which is a key enzyme in triglyceride synthesis in eukaryotic organisms, has been proposed as one of the drug targets for treating obesity, type II diabetes mellitus, and metabolic syndrome. Bioassay-guided fractionation of EtOH extract of the flower buds of Tussilago farfara , using an in vitro DGAT enzyme assay, resulted in the isolation of four known sesquiterpenoids, tussilagonone (1), tussilagone (2), 7beta-(3-ethyl-cis-crotonoyloxy)-1alpha-(2-methylbutyryloxy)-3,14-dehydro-Z-notonipetranone (3), and 8-angeloylxy-3,4-epoxy-bisabola-7(14),10-dien-2-one (4). DGAT1 inhibitory activity was studied by in vitro DGAT assay using rat liver microsomes and HepG2 cell microsomes. They showed DGAT1 inhibition with IC(50) values of 99.2 (1), 18.8 (2), 47.0 (3), and 211.1 (4) microM (for rat liver microsomes) and >1 mM (1), 49.1 (2), 160.7 (3), and 294.4 (4) microM (for HepG2 cell microsomes), respectively. Compound 2 showed the most potent inhibition against microsomal DGAT1 derived from rat liver and human hepatocellular carcinoma HepG2 cells and also significantly inhibited triglyceride synthesis by suppressing incorporation of [(14)C]acetate or [(14)C]glycerol into triglycerides in HepG2 cells. These findings suggest that tussilagone is a potential lead compound in the treatment of obesity and type 2 diabetes.

Medical expenditure of national health insurance attributable to smoking among the Korean population.

OBJECTIVES: The purpose of this study was to determine the population-attributable risk (PAR) and estimate the total medical expenditure of the Korean National Health Insurance (KNHI) due to smoking. METHODS: We used data from the Korean Cancer Prevention Study of 1,178,138 Koreans aged 30 to 95. These data were available from 1992 to 2003 and covered a long-term follow-up period among the Korean population. RESULTS: The total medical expenditure of KNHI related to smoking increased by 27% from $324.9 million in 1999 to $413.7 million in 2003. By specific diseases, smoking-attributable KNHI medical expenditure was the highest for lung cancer ($74.2 million), followed by stroke ($65.3 million), COPD ($50.1 million), CHD ($49 million) and stomach cancer ($30 million). A total of 1.3 million KNHI patients were suffering from smoking-related diseases in 2003. We predicted rises in total KNHI medical expenditure related to smoking to $675.1 million (63% increase compared with that of 2003) and in the total number of KNHI patients suffering from smoking-related diseases to about 2.6 million (an approximate 100% increase compared with those in 2003) in 2015. CONCLUSIONS: We found a substantial economic burden related to the high smoking prevalence in South Korea.

Smoking and cancer risk in Korean men and women.

OBJECTIVE: In Korea, male smoking prevalence is among the world's highest, and mortality rates from smoking-caused cancers, particularly lung cancer, are escalating. This cohort study examined the effects of cigarette smoking on the risk of cancer mortality and incidence, and characterized the relationship of cancer risk with the amount and duration of cigarette smoking. METHOD: A nine-year prospective cohort study was carried out on 1,212,906 Koreans, 30-95 years of age. The study population includes participants in a national insurance program, who completed a questionnaire on smoking and other risk factors. The main outcome measures were death from cancer and cancer incidence, obtained through record linkage. At baseline, 472,970 men (57.0%) and 20,548 (5.4%) women were current cigarette smokers. RESULTS: In multivariate Cox proportional hazards models, controlling for age, current smoking among men increased the risks of mortality for cancer of the lung (relative risk (RR), 4.6; 95% confidence interval (CI), 4.0-5.3) and other cancers, including larynx, bile duct, esophagus, liver, stomach, pancreas, bladder, and also leukemia. Current smoking among women increased the risk of lung cancer mortality (RR = 2.5, 95% CI = 2.0-3.1). Similar results were found for incidence among men and women. CONCLUSION: In Korea, smoking is an independent risk factor for a number of major cancers. The findings affirm the need for aggressive tobacco control in Korea in order to minimize the epidemic of smoking-caused disease.