Transfer of epinastine to infants through human breast milk.

The purpose of this study was to develop an analytical method for analyzing epinastine in breast milk and maternal plasma samples to determine the safety of epinastine in breastfed infants. Six nursing mothers took epinastine hydrochloride (20 mg) once a day for 7 days, while a nursing mother took it for 30 days. Breast milk and blood samples were collected 2, 4, and 10 h after administration from the volunteers. A liquid chromatography-mass spectrometry system was used to analyze samples pretreated by liquid-liquid extractions. The concentration of epinastine in human milk was 10.3-33.5 ng/mL after 2 h, 9.1-63.8 ng/mL after 4 h, and 8.3-28.9 ng/mL after 10 h. The increase achieved 4 h after administration indicates that epinastine was transferred into human breast milk. However, the milk-to-plasma ratio had a wide range (0.82-3.39), while the relative infant dose at 4 h was 0.36-2.49%, which is lower than the safety level of transferability (10%). Moreover, the plasma levels of epinastine in two infants were slightly below the quantification limit. Overall, our results suggested that epinastine can safely be used by nursing mothers without affecting their infants.

The promoting effect of eucommiol from Eucommiae cortex on collagen synthesis.

The effect of a methanol extract of Eucommiae Cortex on collagen synthesis was investigated in false aged model rats. Granuloma formation and collagen synthesis were significantly increased by the administration of the methanol extract of Eucommiae Cortex. The effective component of Eucommiae Cortex was then discussed by fractionating the methanol extract of Eucommiae Cortex. Eucommiol, a main component in the water fraction of the methanol extract, was found to be an effective compound. In our previous paper, we reported the promoting effect of Eucommia ulmoides OLIVER leaf on collagen synthesis, and found geniposidic acid and aucubin were the main effective compounds in the leaf. Based on our data in this paper, we clarified that the main effective components of the Eucommia ulmoides OLIVER leaf and Eucommiae Cortex were different. Geniposidic acid and aucubin were reported to be contained at a high concentration in the fresh cortex of Eucommia ulmoides OLIVER, but during the drying process and storage, most of them were destroyed by enzymes in the cortex and very little remained in the Eucommiae Cortex. Therefore, we investigated the effect of the methanol extract of fresh cortex of Eucommia ulmoides OLIVER. A stronger effect than Eucommiae cortex was shown, and geniposidic acid, aucubin and geniposide were concluded to be the main effective components. Although geniposide was found to be an effective compound, when the dose was higher than 50 mg/kg/d, toxicity was shown. The pharmaceutical effect of eucommiol was reported for the first time.

Granuloma maturation in the rat is advanced by the oral administration of Eucommia ulmoides OLIVER leaf.

We have reported that collagen metabolism was improved by the administration of Eucommia ulmoides OLIVER leaf. In this paper, we examine the granuloma maturation and deposition of collagen in the granuloma of rats due to the oral administration of this leaf. After 3 weeks of the oral administration, granuloma formation was induced by the formalin soaked filter paper-pellet method. A week later, the developing granuloma was dissected. Granuloma formation was significantly increased due to ingestion of the dried leaf at a dose of 1.8 g/kg of body weight/d. The collagen content in the granuloma was also significantly increased. In the case of the collagen profile, the pepsin-solubilized collagen content and its relative percentage to the total collagen were significantly higher than in the control. Histochemical examination showed that the granuloma tissues were well developed, and displayed many newly synthesized capillary vessels and a greater quantity of fibroblasts and monocytes in the 1.8 g leaf group. High density lipoprotein (HDL)-cholesterol and triglyceride content in the blood plasma were significantly higher than in the control. These results show that granuloma maturation was accelerated and the energy was supplied from fatty acid metabolism. The administration of Eucommia ulmoides OLIVER leaf may be effective at speeding up the wound healing process.

Improvement in the turnover rate of the stratum corneum in false aged model rats by the administration of geniposidic acid in Eucommia ulmoides Oliver Leaf.

We earlier reported that collagen synthesis in false aged model rats was stimulated by the administration of a methanol extract from the leaves of Eucommia ulmoides OLIVER. When the methanol extract was fractionated to n-hexane, ethyl acetate, acetone and methanol fractions by silica gel chromatography, we discovered that geniposidic acid and aucubin, contained in the acetone fraction, were the active ingredients. In the current study, we set out to examine if active compounds found in the Eucommia ulmoides OLIVER leaf (EUOL) improved the low turnover rate in the stratum corneum of false aged model rats. The turnover rate in the stratum corneum in rats was measured as 50% dansyl chloride clearance day. In the first experiment, administration of a 2.4% water soluble methanol extract (WSME) of EUOL, along with an 11% protein diet, led to a 20% higher turnover rate in the stratum corneum (p<0.05, Mann-Whitney) than the control value. The WSME mainly contained iridoid mono-glycosides such as geniposidic acid. In the second experiment, treatment with geniposidic acid similarly caused a higher turnover rate in the stratum corneum, increasing turnover by 23% (p<0.05, Mann-Whitney) compared to the control value. In this paper we reveal that the WSME contains compounds effective against aging, and one of them is geniposidic acid.

Protein synthesis in fast and slow muscles of developing cockerels loaded with 2G for 3 weeks.

BACKGROUND: In our previous study, the increment of RNA and protein content ratios against body weight in the whole skeletal muscle were determined in young developing cockerels under 2G hypergravity for 3 weeks. In the present study, protein synthesis rate, RNA activity and protein content were investigated in different types of muscles [slow muscle (soleus) and fast muscle (extensor digitorum longus; EDL)] in similar experimental conditions. HYPOTHESIS: It is believed that slow and fast muscle will show different responses to hypergravity. METHOD: Young cockerels were raised standing vertically in a centrifuge and lived in a hypergravity (2G) environment for 3 weeks. At the end of the 3 weeks, the soleus and EDL muscles in their legs were immediately removed and the protein and RNA extracted. The fractional rate of protein synthesis in the muscles were determined by incorporation of L-[4-3H]-phenylalanine. RESULTS: The feed intake of centrifuged cockerels was reduced on the first day but recovered on the second day. Thus, the growth curve was parallel although 2G-loaded cockerels were smaller in size. In a slow muscle (soleus) the protein synthesis rate, protein content and muscle mass were significantly increased after 2G loading. While fast muscle (EDL) protein synthesis rate (Ks) and RNA activity decreased, muscle mass and protein content had no significant change in the 2G loading group. CONCLUSION: Soleus, which supports the body against gravity, apparently responded to hypergravity, while EDL may be repressed in protein turnover under the same condition. These findings imply that slow and fast muscles show different responses to hypergravity according to their function.

The promoting effects of geniposidic acid and aucubin in Eucommia ulmoides Oliver leaves on collagen synthesis.

We have reported that collagen synthesis was stimulated by the administration of a hot water extract from the leaves of Eucommia ulmoides OLIVER, Eucommiaceae (Du-Zhong leaves) in false aged model rats. In this paper, we set out to examine the compounds in Du-Zhong leaves that stimulated collagen synthesis in false aged model rats. In experiment 1, a methanol extract of Du-Zhong leaves also stimulated collagen synthesis in aged model rats. An acetone fraction was derived from the methanol extract by silica gel chromatography in experiment 2. The acetone fraction mainly contained iridoides mono-glycosides such as geniposidic acid and aucubin. The administration of geniposidic acid or aucubin stimulated collagen synthesis in aged model rats in experiments 3 and 4 (significance (p<0.05)). The reported pharmacological effects of Du-Zhong leaves, including healing organs and strengthening bone and muscle, are closely related to collagen metabolism. It appears that geniposidic acid and aucubin are the actual compounds in Du-Zhong which caused the effect in our experiments.

The preventive effect of ginseng with du-zhong leaf on protein metabolism in aging.

Stimulation of collagen synthesis prevents the aging process. We found such a synergistic effect by using the leaves of Eucommia ulmoides Oliver, Eucomiaceae (Du-Zhong leaf) and the roots of Panax ginseng C. A. MEYER (Ginseng). The formula consists of amounts which exert no effect when used individually. We tested several formula ratios of Ginseng and Du-Zhong leaf, 1:1, 1:2, 1:3 and 1:4, and concluded that the last two formulas were effective. However, we did not observe a significant difference between 1:3 and 1:4. Thus, it was demonstrated that the formula ratio of Ginseng to Du-Zhong leaf of 1:3 was the most effective for the stimulation of collagen synthesis and the prevention of decreased protein metabolism in aging.

Effects of du-zhong leaf extract on serum and hepatic lipids in rats fed a high-fat diet.

We evaluated the effects of Du-Zhong leaf extract on the serum and liver lipids in rats fed a high-fat diet supplemented with animal fat, cholesterol and cholate. The Du-Zhong leaf extract suppressed significantly the high-fat diet-induced increases in total serum cholesterol, serum triacylglycerol and hepatic triacylglycerol but not the total hepatic cholesterol. The Du-Zhong leaf extract also suppressed the high-fat diet induced increases in very-low density lipoprotein and low density lipoprotein without affecting high density lipoprotein cholesterol. These results suggest that Du-Zhong leaf extract may be beneficial for the regulation of hyperlipidemia.

Inhibitory effects of berberine-type alkaloids on elastase.

Berberine-type alkaloids and some structurally related alkaloids were tested for inhibitory activity on porcine pancreatic elastase (PPE) and human sputum elastase (HSE). The chlorides of berberine, coptisine, and sanguinarine significantly inhibited the elastolytic activity of both the enzymes, but tetrahydroberberine had no effect on the activity. It seems that the quaternary nitrogen of the alkaloids plays an important role in the inhibition of elastolytic activity. Amidolytic activity of the elastases was not affected by any of the alkaloids tested.

[Studies on collagenase inhibitors. IV. Inhibitors of bacterial collagenase in Coptidis rhizoma].

A hot aqueous extract of Coptidis Rhizoma had an inhibitory effect on the bacterial collagenase from Clostridium histolyticum. Active principles were isolated by silica gel column chromatography from the CHCl3 extract. Consequently, two inhibitors obtained were identified with the chloride of berberine and coptisine. The concentrations of the berberine and coptisine in the assay mixture to give 50% inhibition (IC50) were 0.73 mM and 0.16 mM, respectively. The type of inhibition by coptisine chloride was shown to be a mixture type from Lineweaver-Burk plots. Tetrahydroberberine, a reduction product of berberine chloride, had no inhibitory effect. This result suggests that the quaternary nitrogen of the alkaloids plays an important role in inhibitory activity.

[Studies on collagenase inhibitors. III. Inhibitory effects of anthracyclines on bacterial collagenase].

Inhibitory effects of anthracyclines on bacterial collagenase were examined. Daunomycin, doxorubicin, and aclarubicin potently inhibited the collagenase, but mitomycin C and 5-fluorouracil did not inhibit. Inhibitory activities of anthracyclines were constant regardless of the concentrations of Ca2+, activator of collagenase, or of Zn2+, active center of collagenase. These results suggest that the inhibitory mechanisms of anthracyclines were independent of a chelate effect on Ca2+ or Zn2+.

[Studies on collagenase inhibitors. II. Inhibitory effects of anthraquinones on bacterial collagenase].

The inhibitory activities of 44 anthraquinones against bacterial collagenase were assayed in vitro. Emodin (1,6,8-trihydroxy-3-methylanthraquinone, 41) was the most potent active inhibitor among them (IC50; 4.0 X 10(-5) M). The type of inhibition by 41 was found to be a mixture type by use of Lineweaver-Burk plots. Since the inhibitory activities of anthraquinones were not affected by the concentration of Ca2+ in the assay medium, it is considered that the inhibitory mechanism is not a chelate effect on Ca2+. In mono-substituted anthraquinones, the compounds which have a substituent (OH or SO3Na) at 2-position show more potent inhibitory activity than the corresponding 1-substituted compound.

[Effects of lamprey oil prepared under different deodorization conditions on serum lipids, reticuloendothelial system and antibody production in mice].

Fresh lamprey oil (F-La) is known to contain a large amount of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. When F-La was deodorized with steam at 280 degrees C and 1 mmHg for 1 h, the contents of EPA and DHA were reduced and unidentified peaks were detected by gas-liquid chromatography. In male ddY mice, one week feeding of the lamprey oil deodorized at 280 degrees C (H-La) remarkably decreased the serum triglyceride level and increased the liver weight 2.0-fold. H-La also lowered the corrected phagocytic index (alpha), which is an indicator of activities of reticuloendothelial system, but suppressed relatively little the antibody production against sheep red blood cells. It is suggested that H-La contains biologically active substances, which have potent hepatotoxic and serum triglyceride-reducing effects. This biologically active substances appear to be derived from long-chain polyunsaturated fatty acids under thermal deodorization conditions.

Protection of the rat myocardium from ischemic injury by dietary lamprey oil.

The lamprey (Entosphenus japonicus Martens) has been recommended in Japan as an efficacious diet for curing some of chronic inflammatory disorders. Fresh lamprey is rich in n-3 unsaturated fatty acids (e.g., eicosapentaenoic and docosahexaenoic acids) with minimal seasonal variation. The dietary effect of lamprey oil on acute myocardial ischemia was therefore investigated. Rats were fed a control diet or a diet supplemented with 5% safflower oil (SO) or 5% lamprey oil (LO) for 4 weeks. After coronary artery ligation, rats fed the LO diet demonstrated a higher 24-h survival rate and a reduced loss of creatine kinase activity from ischemic myocardium when compared with rats fed the control or SO diet. Moreover, the intracellular redistribution of lysosomal enzyme activity in the ischemic myocardium was significantly suppressed in the LO diet group. Analysis of the fatty acid composition of myocardial phospholipids in rats fed LO showed marked elevation of n-3 fatty acids, whereas arachidonic acid (n-6) content was significantly reduced. Hence, the n-3/n-6 ratio of myocardial phospholipids was markedly increased in the LO diet group. In addition, there was more than a 77% reduction in TXB2 synthetic capacity in whole blood in rats fed the LO diet when compared with rats fed either the control or SO diet. In conclusion, dietary supplementation with LO prevents sudden cardiac death and limits the extension of cellular damage from acute myocardial ischemia in rats. Both changes in thromboxane generation and altered membrane fatty acid composition may be involved in the observed reduction of ischemic damage in the heart.