Development of p-Coumaric Acid Analysis in Human Plasma and Its Clinical Application to PK/PD Study.

It has been recognized that p-Coumaric acid (p-CA) has protective effects as an antioxidant, anti-inflammatory agent. A sensitive and efficient Liquid Chromatography-Mass Spectrometry (LC-MS) method for maximum determination of p-CA in human plasma has been established using Ultra-performance liquid Chromatography-tandem mass Spectrometry (UPLC-MS/MS). This study provides the developed analysis of p-CA extracted from Bambusae Caulis in Taeniam (BC) to examine the improvement of the treatment p-CA, IGF-1 and Osteocalcin level in human children which are important factors on the growth of children's height through Pharmacokinetics/Pharmacodynamics (PK/PD) model. p-CA and internal standard in a plasma sample were detected by the Multiple Reaction Monitoring (MRM) scan mode with positive ion detection. The sample participating in the study was made of 34 subjects (placebo = 18, treatment = 16). The subjects were enrolled to be randomized to the control group and BC group. Randomized subjects took tested treatment twice a day, three capsules with oral administration (258 mg/capsule) each time after a meal. Standard calibration curves (reproducibility) were constructed and the lower limit of quantitation (LLOQ) for p-CA was found to be 0.2 ng/mL on injection of the sample into the UPLC-MS/MS system. Accuracy and precision were evaluated and the intra-accuracy was 99.2-103.8% with precision of 1.0-5.6% and inter-accuracy was 99.6-108.4% and precision of 1.3-6.4% for p-CA. The method has been successfully applied to PK/PD studies of p-CA in human plasma. The p-CA, BC in Taeniam extract increased the level of IGF-1 and Osteocalcin, and changed the height from baseline, which suggested that the p-CA could play an important role in longitudinal bone growth. Therefore, the p-CA extracted from BC in Taeniam might be a good alternative medicine to growth hormone (GH) therapy.

Effects of a combination treatment of KD5040 and L-dopa in a mouse model of Parkinson's disease.

BACKGROUND: Although the dopamine precursor L-3, 4-dihydroxyphenylalanine ( l -dopa) remains the gold standard pharmacological therapy for patients with Parkinson's disease (PD), long-term treatment with this drug has been known to result in several adverse effects, including l -dopa-induced dyskinesia (LID). Recently, our group reported that KD5040, a modified herbal remedy, had neuroprotective effects in both in vitro and in vivo models of PD. Thus, the present study investigated whether KD5040 would have synergistic effects with l -dopa and antidyskinetic effects caused by l -dopa as well. METHODS: The effects of KD5040 and l -dopa on motor function, expression levels of substance P (SP) and enkephalin (ENK) in the basal ganglia, and glutamate content in the motor cortex were assessed using behavioral assays, immunohistochemistry, Western blot analyses, and liquid chromatography tandem mass spectrometry in a mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In addition, the antidyskinetic effects of KD5040 on pathological movements triggered by l -dopa were investigated by testing abnormal involuntary movements (AIMs) and measuring the activations of FosB, cAMP-dependent phosphor protein of 32 kDa (DARPP-32), extracellular signal-regulated kinases (ERK), and cAMP response element-binding (CREB) protein in the striatum. RESULTS: KD5040 synergistically improved the motor function when low-dose l -dopa (LL) was co-administered. In addition, it significantly reversed MPTP-induced lowering of SP, improved ENK levels in the basal ganglia, and ameliorated abnormal reduction in glutamate content in the motor cortex. Furthermore, KD5040 significantly lowered AIMs and controlled abnormal levels of striatal FosB, pDARPP-32, pERK, and pCREB induced by high-dose l -dopa. CONCLUSIONS: KD5040 lowered the effective dose of l -dopa and alleviated LID. These findings suggest that KD5040 may be used as an adjunct therapy to enhance the efficacy of l -dopa and alleviate its adverse effects in patients with PD.

F-series prostaglandin function as sex pheromones in the Korean salamander, Hynobius leechii.

In order to test whether prostaglandins (PGs) function as sex pheromones in Hynobius leechii, a salamander that externally fertilizes its eggs, we conducted electro-olfactogram (EOG) studies with 19 PGs, liquid chromatography tandem mass spectrometry (LC-MS/MS) analyses of female and male holding waters, and behavioral tests on selected PGs. Of the 19 PGs tested, only three induced strong EOG responses from both males and ovulated females: 15-epi-prostaglandin F2alpha (15(R)-PGF2alpha), 15-keto-prostaglandin F2alpha (15K-PGF2alpha), and 13,14-dihydro-15-keto-prostaglandin F2alpha (13,14-dh-15K-PGF2alpha). In the LC-MS/MS studies, samples of holding water from ovulated females contained higher concentrations of 15(R)-PGF2alpha, PGF2alpha, and 13,14-dh-15K-PGF2alpha than those from males or oviposited females. In the behavioral tests, only 15(R)-PGF2alpha and ovulated female holding water induced significant reproductive behavior from male salamanders. These results suggest that F-series prostaglandins function as sex pheromones in amphibians.

Evaluation of malodor for automobile air conditioner evaporator by using laboratory-scale test cooling bench.

As one of the measures to improve the environment in an automobile, malodor caused by the automobile air-conditioning system evaporator was evaluated and analyzed using laboratory-scale test cooling bench. The odor was simulated with an evaporator test cooling bench equipped with an airflow controller, air temperature and relative humidity controller. To simulate the same odor characteristics that occur from automobiles, one previously used automobile air conditioner evaporator associated with unpleasant odors was selected. The odor was evaluated by trained panels and collected with aluminum polyester bags. Collected samples were analyzed by thermal desorption into a cryotrap and subsequent gas chromatographic separation, followed by simultaneous olfactometry, flame ionization detector and identified by atomic emission detection and mass spectrometry. Compounds such as alcohols, aldehydes, and organic acids were identified as responsible odor-active compounds. Gas chromatography/flame ionization detection/olfactometry combined sensory method with instrumental analysis was very effective as an odor evaluation method in an automobile air-conditioning system evaporator.

Expression and RNA interference-induced silencing of the dammarenediol synthase gene in Panax ginseng.

Panax ginseng is one of the most highly valued herbal medicines in the Orient, where it has gained an almost magical reputation for being able to maintain the quality of life. The root of ginseng contains noble tetracyclic triterpenenoid saponins, which are thought to be the major effective ingredients in P. ginseng. The first committed step in ginsenoside synthesis is the cyclization of 2,3-oxidosqualene to dammarenediol II by oxidosqualene cyclase, dammarenediol synthase (DDS). The gene encoding DDS has been characterized. Here, we investigated the expression of the DDS gene together with the genes involved in ginsenoside biosynthesis (SS, SE, PNX, PNY, PNY2 and PNZ). Expression of DDS mRNA was higher in flower buds compared with root, leaf and petiole of ginseng plants. Elicitor (methyl jasmonate) treatment up-regulated the expression of DDS mRNA. Ectopic expression of DDS in a yeast mutant (erg7) lacking lanosterol synthase resulted in the production of dammarenediol and hydroxydammarenone which were confirmed by liquid chromatography-atmospheric pressure chemical ionization mass spectrometry (LC/APCIMS). RNA interference (RNAi) of DDS in transgenic P. ginseng resulted in silencing of DDS expression which leads to a reduction of ginsenoside production to 84.5% in roots. These results indicate that expression of DDS played a vital role in the biosynthesis of ginsenosides in P. ginseng.