Psychological well-being and green tea consumption are associated with lower pentosidine serum levels among elderly female residents in Japan.

OBJECTIVE: Pentosidine (PEN), a well-defined advanced glycation end product (AGE), may be affected by psychological status, given the recent findings regarding AGE receptor functions. Because AGEs can be a factor in aging and in the development or worsening of many degenerative diseases, it is important to find a way to reduce the PEN levels in our body. This study aims to investigate novel factors associated with PEN levels. METHODS: A cross-sectional study involving 106 female participants (aged 59-69) was conducted in a tea-producing district in Japan. The serum concentration of PEN was detected and evaluated in relation to the participants' psychological status, which was assessed using the Japanese version of the 28-item General Health Questionnaire (GHQ) and lifestyle factors. Factors that were significantly associated with PEN were analysed using multiple linear regression analyses. Significance was defined as p < .05. RESULTS: The serum PEN concentrations were significantly and positively associated with the total GHQ scores and BMI after controlling for covariates (standardised beta coefficient (B) = 0.26, p < .01; B = 0.27, p < .01, respectively). In addition, the PEN levels were significantly lower in participants who consumed seven cups or more of green tea per day than those who consumed six or fewer cups per day (B = 0.19, p < .05). CONCLUSIONS: Low GHQ scores (i.e. better psychological well-being) and green tea consumption may be helpful in decreasing AGEs.

Degradation rates and products of fluticasone propionate in alkaline solutions.

The apparent degradation rate constant of fluticasone propionate (FLT) in 0.1 M NaOH:methanol=1:1 at 37 °C was previously reported to be 0.169±0.003 h-1, and four degradation products (products 1-4) were observed in the solution. The aims of the present study were to assess the degradation rates of FLT in other alkaline solutions and clarify the chemical structures of the four degradation products in order to obtain basic data for designing an enema for inflammatory bowel disease. The apparent degradation rate constants in 0.05 M NaOH and 0.1 M NaOH:CH3CN=1:1 were 0.472±0.013 h-1 and 0.154±0.000 h-1 (n=3), respectively. The chemical structures of products 1-4 in 0.1 M NaOH:methanol=1:1 were revealed by nuclear magnetic resonance (NMR) and mass spectrometry data. The chemical structure of products 2 was that the 17-position of the thioester moiety of FLT was substituted by a carboxylic acid. The degradation product in 0.1 M NaOH:CH3CN=1:1 was found to be product 2 based on 1H NMR data. The degradation product in 0.05 M NaOH was considered to be product 2 based on the retention time of HPLC. These results are useful for detecting the degradation products of FLT by enzymes of the intestinal bacterial flora in the large intestine after dosing FLT as an enema.

Degradation rates and products of fluticasone propionate in alkaline solutions / 药物分析学报

The apparent degradation rate constant of fluticasone propionate (FLT) in 0.1 M NaOH:methanol=1:1 at 37 ℃ was previously reported to be 0.169 ± 0.003 h?1, and four degradation products (products 1–4) were observed in the solution. The aims of the present study were to assess the degradation rates of FLT in other alkaline solutions and clarify the chemical structures of the four degradation products in order to obtain basic data for designing an enema for inflammatory bowel disease. The apparent degradation rate constants in 0.05 M NaOH and 0.1 M NaOH:CH3CN=1:1 were 0.472 ± 0.013 h?1 and 0.154 ± 0.000 h?1 (n=3), respectively. The chemical structures of products 1–4 in 0.1 M NaOH:methanol=1:1 were revealed by nuclear magnetic resonance (NMR) and mass spectrometry data. The chemical structure of products 2 was that the 17-position of the thioester moiety of FLT was substituted by a carboxylic acid. The degradation product in 0.1 M NaOH:CH3CN=1:1 was found to be product 2 based on 1H NMR data. The degradation product in 0.05 M NaOH was considered to be product 2 based on the retention time of HPLC. These results are useful for detecting the degradation products of FLT by enzymes of the intestinal bacterial flora in the large intestine after dosing FLT as an enema.

Degradation rates and products of fluticasone propionate in alkaline solutions / 药物分析学报

The apparent degradation rate constant of fluticasone propionate (FLT) in 0.1 M NaOH:methanol=1:1 at 37 ℃ was previously reported to be 0.169 ± 0.003 h?1, and four degradation products (products 1–4) were observed in the solution. The aims of the present study were to assess the degradation rates of FLT in other alkaline solutions and clarify the chemical structures of the four degradation products in order to obtain basic data for designing an enema for inflammatory bowel disease. The apparent degradation rate constants in 0.05 M NaOH and 0.1 M NaOH:CH3CN=1:1 were 0.472 ± 0.013 h?1 and 0.154 ± 0.000 h?1 (n=3), respectively. The chemical structures of products 1–4 in 0.1 M NaOH:methanol=1:1 were revealed by nuclear magnetic resonance (NMR) and mass spectrometry data. The chemical structure of products 2 was that the 17-position of the thioester moiety of FLT was substituted by a carboxylic acid. The degradation product in 0.1 M NaOH:CH3CN=1:1 was found to be product 2 based on 1H NMR data. The degradation product in 0.05 M NaOH was considered to be product 2 based on the retention time of HPLC. These results are useful for detecting the degradation products of FLT by enzymes of the intestinal bacterial flora in the large intestine after dosing FLT as an enema.

Study on health hazards through medicines purchased on the Internet: a cross-sectional investigation of the quality of anti-obesity medicines containing crude drugs as active ingredients.

BACKGROUND: Weight-loss medicines, including crude drugs and herbal supplements disguised as diet-aid products, are readily obtainable and distributed widely, especially in Southeast Asia. Even if such products are unapproved or prescription-only medicines, consumers can purchase them through an agency or directly on the Internet. We evaluated the quality and safety of herbal products purchased on the Internet to reveal their influence on public health. METHODS: Diet-aid products containing Bukuryo (Poria sclerotium), Bakumondo (Ophiopogonis tuber), or Daio (rhubarb rhizome) were purchased through websites that did not provide physical addresses or which advertised misleading medicines (e.g., unapproved Cialis 100 mg tablets, Viagra 100 mg tablets) on websites. We carefully noted details in the descriptions on package inserts or accompanying product characteristics and analyzed the ingredients using qualitative and quantitative methods, namely high-performance liquid chromatography equipped with a photodiode array detector. We requested the respective manufacturers to authenticate their products through a structured questionnaire. RESULTS: We purchased 15 items from 15 Internet sites and imported all 15 items to Japan. One item stated to contain rhubarb rhizome was identified as a prescription medicine; the others were dietary supplements and not medicines. Even though we did not analyze the constituents of all crude drugs, we found some active ingredients in the items. Sibutramine was detected in items confirmed to be supplements, including those containing Poria sclerotium and Ophiopogonis tuber. Each capsule contained ≈ 12 mg of sibutramine, which is the daily dose for anti-obesity medicines. Sibutramine is not approved for use in Japan and its sale has been suspended in Europe and the USA owing to serious adverse effects on the circulatory system. CONCLUSIONS: Our findings indicate that dietary supplements containing injurious ingredients are distributed to Japanese consumers and potentially to a broader international audience, and that purchasing them through unreliable websites bears potential health risks. To avoid potential adverse events, there should be adequate alerts about the risks of taking products without appropriate indications.

Inhibitory effects of catechin derivatives on mammalian DNA polymerase and topoisomerase activities and mouse one-cell zygote development.

In this study, the inhibitory activities against DNA polymerases (pols) and DNA topoisomerases (topos) by eight major green tea catechin derivatives (flavan-3-ols) were investigated. Some catechins inhibited mammalian pols (α and ß) and human topos (I and II), with (-)-epigallocatechin gallate (EGCg) the strongest inhibitor of both enzyme types, showing IC(50) values of 3.8-21.5 and 2.0-20.0 µM, respectively. EGCg did not affect the activities of plant (cauliflower) pol α or prokaryotic pols and showed no effect on the activities of other DNA metabolic enzymes tested. Next, a method was established for assay of mouse one-cell zygote development inhibition, the catechin derivatives screened for bioactivity, and the inhibition was assessed and their effects ranked as: EGCg > GCg > Cg >> others. In the mouse one-cell zygote assay, EGCg at 50 µM increased abnormal cells and 75 µM of EGCg-induced apoptosis. The observed ranking of catechin derivative inhibition effects against mouse one-cell zygote development in vivo was similar to their ranking by topo inhibition in vitro rather than by pol inhibition; therefore, topo inhibition might have been effecting zygote development inhibition. These results suggested that catechin derivatives indeed reached the nuclear DNA where topo inhibition can occur, thus causing the observed cellular effects. From these findings, this zygote development inhibition assay will be useful as an anti-pregnant agent screening.

Profiles of lipid components, fatty acid distributions of triacylglycerols and phospholipids in Jack beans (Canavalia gladiata DC.).

Endogenous tocopherols in extracted lipids from Jack beans (Canavalia gladiata DC.) were determined by high-performance liquid chromatography (HPLC), and were investigated in relation to the fatty acids (FA) distribution of triacylgycerols (TAG) and phospholipids (PL). The dominant tocopherols were (δ)-tocopherol (78.9-96.5mg%) and (γ)-tocopherol (42.1-56.1mg%) with much smaller amounts of (α)-tocopherol (1.1-1.3mg%). The lipids of Jack beans comprised mainly TAG (34.6-38.6 wt.%) and PL (54.8-57.4 wt.%), and other components were also detected in minor proportions (0.3-3.8 wt.%). The PL components included phosphatidyl choline (46.2-48.7 wt.%), phosphatidyl inositol (23.4-29.6 wt.%) and phosphatidyl ethanolamine (18.5-21.2 wt.%). Comparison of these different beans showed, with a few exceptions, no significant differences (P>0.05) in FA distribution. The FA distribution of TAG among the five beans was evident in the Jack beans: unsaturated FA (93.3-95.3 wt.%) were predominantly concentrated at the sn-2 position and saturated FA (33.6-34.4 wt.%) primarily occupying the sn-1 position or sn-3 position. The results obtained from this work would provide useful information to both producers and consumers for manufacturing functional foods or beverages in Japan and elsewhere.

Inhibition of P-glycoprotein-mediated transport by terpenoids contained in herbal medicines and natural products.

Terpenoids form a large and structurally diverse family of natural products and are ingredients of various herbal medicines. We have investigated possible interactions between herbal medicines and conventional medicines, and recently reported that monoterpenoids contained in Zanthoxyli Fructus can be potent inhibitors of P-glycoprotein (P-gp). In the present study, the influence of 70 kinds of terpenoids present in natural products on P-gp-mediated efflux transport was investigated. LLC-GA5-COL150 cells transfected with human MDR1 cDNA encoding P-gp were used to screen the terpenoids. Large increases in the intracellular accumulation of [(3)H]digoxin were observed in the presence of (R)-(+)-citronellal, (S)-(-)-beta-citronellol, alpha-terpinene, terpinolene, (-)-beta-pinene, abietic acid, ophiobolin A, cucurbitacin I, and glycyrrhetic acid. A study of the concentration-dependency revealed that the IC(50) of ophiobolin A, glycyrrhetic acid, (R)-(+)-citronellal, abietic acid, and cucurbitacin I was smaller than that of verapamil. The transcellular transport of [(3)H]digoxin across Caco-2 cell monolayers was then examined in the presence of (R)-(+)-citronellal, abietic acid, and glycyrrhetic acid. Significant increases in the apical-to-basolateral transport and decreases in the basolateral-to-apical transport and efflux ratio were demonstrated. These findings suggest that some natural products containing these terpenoids may inhibit P-gp-mediated transport and interact with P-gp substrates in the intestinal absorption process.

Inhibition of P-glycoprotein-mediated transport by extracts of and monoterpenoids contained in Zanthoxyli fructus.

Citrus (rutaceous) herbs are often used in traditional medicine and Japanese cuisine and can be taken concomitantly with conventional medicine. In this study, the effect of various citrus-herb extracts on P-glycoprotein (P-gp)-mediated transport was examined in vitro to investigate a possible interaction with P-gp substrates. Component monoterpenoids of the essential oil in Zanthoxyli fructus was screened to find novel P-gp inhibitors. LLC-GA5-COL150 cells transfected with human MDR1 cDNA encoding P-gp were used. Cellular accumulation of [3H]digoxin was measured in the presence or absence of P-gp inhibitors or test samples. Aurantii fructus, Evodiae fructus, Aurantii fructus immaturus, Aurantii nobilis pericarpium, Phellodendri cortex, and Zanthoxyli fructus were extracted with hot water (decocted) and then fractionated with ethyl acetate. The cell to medium ratio of [3H]digoxin accumulation increased significantly in the presence of the decoction of Evodiae fructus, Aurantii nobilis pericarpium, and Zanthoxyli fructus, and the ethyl acetate fraction of all citrus herbs used. The ethyl acetate fraction of Zanthoxyli fructus exhibited the strongest inhibition of P-gp among tested samples with an IC50 value of 166 microg/mL. Then its component monoterpenoids, geraniol, geranyl acetate, (R)-(+)-limonene, (R)-(+)-linalool, citronellal, (R)-(+)-citronellal, DL-citronellol, (S)-(-)-beta-citronellol, and cineole, were screened. (R)-(+)-citronellal and (S)-(-)-beta-citronellol inhibited P-gp with IC50 values of 167 microM and 504 microM, respectively. These findings suggest that Zanthoxyli fructus may interact with P-gp substrates and that some monoterpenoids with the relatively lower molecular weight of about 150 such as (R)-(+)-citronellal can be potent inhibitors of P-gp.

Galectin-9 induces apoptosis through the calcium-calpain-caspase-1 pathway.

Galectin-9 (Gal-9) induced the apoptosis of not only T cell lines but also of other types of cell lines in a dose- and time-dependent manner. The apoptosis was suppressed by lactose, but not by sucrose, indicating that beta-galactoside binding is essential for Gal-9-induced apoptosis. Moreover, Gal-9 required at least 60 min of Gal-9 binding and possibly de novo protein synthesis to mediate the apoptosis. We also assessed the apoptosis of peripheral blood T cells by Gal-9. Apoptosis was induced in both activated CD4(+) and CD8(+) T cells, but the former were more susceptible than the latter. A pan-caspase inhibitor (Z-VAD-FMK) inhibited Gal-9-induced apoptosis. Furthermore, a caspase-1 inhibitor (Z-YVAD-FMK), but not others such as Z-IETD-FMK (caspase-8 inhibitor), Z-LEHD-FMK (caspase-9 inhibitor), and Z-AEVD-FMK (caspase-10 inhibitor), inhibited Gal-9-induced apoptosis. We also found that a calpain inhibitor (Z-LLY-FMK) suppresses Gal-9-induced apoptosis, that Gal-9 induces calcium (Ca(2+)) influx, and that either the intracellular Ca(2+) chelator BAPTA-AM or an inositol trisphosphate inhibitor 2-aminoethoxydiphenyl borate inhibits Gal-9-induced apoptosis. These results suggest that Gal-9 induces apoptosis via the Ca(2+)-calpain-caspase-1 pathway, and that Gal-9 plays a role in immunomodulation of T cell-mediated immune responses.