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Purpose: To determine the antioxidant and hepatoprotective effects of decursin and decursinol angelate (D/DA) isolated from Angelica gigas Nakai (AGN).Methods: The 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity of D/DA was assessed in a rat model using blood tests, western blotting, and histopathological analyses to identify the pharmaceutical effects of D/DA on liver enzymes and liver morphology.Results: The DPPH scavenging activity of D/DA was 47.11 μg/mL. Administration of D/DA to carbon tetrachloride (CCl4)-treated rats led to a decrease (13.59 %) in the total liver mass of control rats. Decursin and decursinol angelate also lowered the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), but increased the concentrations of antioxidant enzymes in the liver, including catalase (CAT) and glutathione peroxidase (GPx). Histological examination revealed that D/DA also reduced hepatocellular damage in the rats.Conclusion: D/DA from AGN has significant anti-hepatotoxic and antioxidant activities, and thus, is a potential herbal drug for treating liver damage. Keywords: Decursin, Decursinol angelate, Antihepatotoxicity, Antioxidant, Angelica gigas Nakai

Angelicae Gigantis Radix (AGR, Angelica gigas) has been used for a long time as a traditional folk medicine in Korea and oriental countries. Decursinol angelate (DCA) is structurally isomeric decursin, one of the major components of AGR. This study was performed to confirm whether DCA augments pentobarbital-induced sleeping behaviors via the activation of GABAA-ergic systems in animals. Oral administration of DCA (10, 25 and 50 mg/kg) markedly suppressed spontaneous locomotor activity. DCA also prolonged sleeping time, and decreased the sleep latency by pentobarbital (42 mg/kg), in a dose-dependent manner, similar to muscimol, both at the hypnotic (42 mg/kg) and sub-hypnotic (28 mg/kg) dosages. Especially, DCA increased the number of sleeping animals in the sub-hypnotic dosage. DCA (50 mg/kg, p.o.) itself modulated sleep architectures; DCA reduced the counts of sleep/wake cycles. At the same time, DCA increased total sleep time, but not non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. In the molecular experiments. DCA (0.001, 0.01 and 0.1 µg/ml) increased intracellular Cl- influx level in hypothalamic primary cultured neuronal cells of rats. In addition, DCA increased the protein expression of glutamic acid decarboxylase (GAD65/67) and GABAA receptors subtypes. Taken together, these results suggest that DCA potentiates pentobarbital-induced sleeping behaviors through the activation of GABAA-ergic systems, and can be useful in the treatment of insomnia.

Pyrethroids, organic compounds similar to natural pyrethrums, constitute the majority of insecticides. Pyrethroids are widely used around the world owing to their excellent selective toxicity to certain insects. In addition, they are easily found in daily life, accounting for most household pesticides. Owing to the easy access to pyrethroid insecticides, pyrethroid-related accidents and suicides have occurred yearly. For the first time, nine pyrethroids commonly used in South Korea and their seven major metabolites were simultaneously analyzed and validated in human plasma using liquid chromatography triple quadrupole mass spectrometry. Plasmas spiked with these pyrethroids and their metabolites were prepared and deproteinized via the addition of acetonitrile. This deproteinized supernatant was filtered and directly injected to ascertain the liquid chromatography-tandem mass spectrometry. For a sensitive and reproducible analysis, all the pyrethroid and metabolite analysis conditions for the multiple reaction monitoring mode were optimized in advance and employed. The validation parameters of the method, including the specificity, linearity, limit of detection, limit of quantification, accuracy, precision, recovery, matrix effect, and stability were also evaluated. The R2 value of linearity was greater than 0.997 for all the analytes, the accuracy ranged from 81.8% to 112.3%, the precision from 0% to 10.1%, and the recovery from 90.9% to 112.4%, depending on the analyte. The stability was 97.0% to 107.0% in fresh plasma and 97.6% to 107.7% in corrupt plasma. The results were satisfactory for all the validation parameters. Furthermore, authentic pyrethroid-poisoned samples were analyzed using this validation method, to determine the suitability; deltamethrin and its metabolites, cis-DBCA and 3-PBA, were successfully analyzed.

Metabolite profiling of postmortem blood in carbon monoxide poisoning cases was performed with gas chromatography-mass spectrometry based on metabolomics. All data were processed with an automated mass spectral deconvolution and identification system and the metabolites were characterized using the National Institute of Standards and Technology library. Discriminant analysis was performed and the carbon monoxide-induced biomarkers were determined with a variable importance parameter in the projection plot obtained from partial least square discriminant analysis. This metabolomics approach, including global metabolites profiling, is useful in improving the interpretation of metabolism in carbon monoxide poisoning deaths.

Scientists have recently shown an interest in the characteristics of Bacillus mojavensis strains because of their increasing use in plants as a defense against diseases and mycotoxins. We have shown here that B. mojavensis KJS-3 possesses the typical characteristics of B. mojavensis strains including a strong resistance to high temperatures (≤50°C), tolerance to high salt concentrations (7% NaCl), ethanol tolerance (40% ethanol), and pH range for growth (pH 5-9). B. mojavensis KJS-3 has been used for the production of cyclic lipopeptides including important antifungal substances such as surfactin, iturin, and fengycin. Polymerase chain reaction analysis in this study showed that B. mojavensis KJS-3 can be used for the production of fengycin and the findings of LC-MS/MS analyses suggest that B. mojavensis KJS-3 can be used to produce iturin and surfactin. Antifungal activity analys is confirmed that B. mojavensis KJS-3 has antifungal effects on Botrytis cinerea, Rhizoctonia solani AG-4, Sclerotinia sclerotiorum, and Colletotricum goeosporioides. A microscopy assessment of the roots of wild ginseng plants planted together with B. mojavensis KJS-3 revealed that the roots contained B. mojavensis KJS-3, confirming the bacteria to be a plant growth promoting endophyte (PGPE) which acts against plant diseases and mycotoxins. Our findings lead us to conclude that B. mojavensis KJS-3 can be produced at an industrial level as a microbial pesticide or microbial fertilizer.

One of the strains of the Bacillus mojavensis group, Bacillus mojavensis KJS-3 (B. mojavensis KJS-3), which has been demonstrated to play a role in protecting plants against diseases as a bacterial endophyte and in reducing the accumulation of mycotoxins generated by an endophytic fungus, was recently discovered in food waste. In this study, the identification and characterization of B. mojavensis KJS-3 was performed via TEM analysis, API-zym test, API 50 CHB test, assays of catalase and oxidase activity, lactic acid production, stability under various conditions, antibiotic susceptibility, and cellular fatty acid composition. The overall results of this study demonstrate that B. mojavensis KJS-3 may have great potential as a probiotic product, as this bacterium is quite stable in somewhat harsh environments. B. mojavensis KJS-3 was positive on oxidase and catalase tests, and the conversion rate of glucose to lactic acid was 58.9%. Finally, anteiso-C(15:0) (43.10%) was identified as the major fatty acid.

Even though salmon calcitonin (sCT) has been known as a potent hypocalcemic agent, only injection or nasal spray products are available on the market. In order to develop oral delivery system of the agent, a novel sCT-sodium tripolyphosphate (STPP) ionic complex was fabricated and also characterized. For the optimization of the ionic complexation, the effect of incubation time and molar ratio between sCT and STPP was evaluated. Particle size of the ionic complex in aqueous media, SEM images, DSC, FT-IR, in vitro release test, stability within the simulated intestinal fluid, and hypocalcemic effect were evaluated. The optimal molar complexation ratio of sCT to STPP was ranged from 1:5 to 1:10 and the complexation efficiency was about 95%. The SEM image has shown that the freeze dried ionic complex has rough morphology in their surface and the particle size in PBS (pH 7.4) was about 220nm. The DSC and FT-IR results provided evidences for ionic interaction between -NH(2) groups and -P horizontal lineO groups of sCT and STPP, respectively. The sCT ionic complex has shown sustained sCT releasing characteristics for 3weeks. The sCT-STPP ionic complex was protective to enzymatic attack and in vivo animal data revealed that the present ionic complex would show continuous hypocalcemic effect. Conclusively, the present sCT-STPP ionic complex formulation thought to be a novel oral delivery candidate for the treatment of osteoporosis.

Five kinds of coumarin compounds were successfully purified from Angelica gigas Nakai by using recyclingpreparative HPLC and identified as decursin (1), decursinol angelate (2), 7-demethylsuberosine (3), marmesin (4), and decursinol (5) by NMR analyses. None of the purified compounds in ethanol showed DPPH radical scavenging activity, while the A. gigas extract (AGNEX) displayed a significant level of activity. Interestingly, compounds 3 in phosphate buffered saline (PBS) showed good ABTS + radical scavenging activity (IC 50 =8.1 ㎍/mL) as did compounds 4 and 5. The anti-inflammatory activities of the purified compounds were evaluated and compared using the NO concentration assay and western blot analysis on LPS-stimulated RAW 264.7 cells. NO production was significantly suppressed by all the compounds in a dose-dependent manner among which compounds 1, 2, and 3 showed very good activities with IC 50 values of 7.4, 6.5, and 7.6 ㎍/mL, respectively. Treatment with compounds 1-5 effectively suppressed the expression levels of iNOS, IL-1β, and COX-2, which are responsible for promoting the inflammatory process. Thus, the ethanol extract and coumarin compounds of A. gigas Nakai hold promise for use as potential anti-inflammatory agents.

The identification and characterization of Bacillus polyfermenticus KJS-2 (B. polyfermenticus KJS-2) was conducted using TEM, an API 50CHB kit, 16S rDNA sequencing, a phylogenetic tree, and catalase and oxidase testing. The conversion rate of glucose to lactic acid by B. polyfermenticus KJS-2 was found to be 60.71+/-4.9%. In addition, treatment of B. polyfermenticus KJS-2 with artificial gastric juice (pH 2.0) and bile acid (pH 6.5) for 4 h resulted in a final viability of 140+/-7.9% and 108+/-3.5%, respectively. Finally, the results of adhesion experiments using Caco-2 cells revealed that the adherence of B. polyfermenticus KJS-2 to Caco-2 cells was approximately 65+/-0.6%.

Bacillus polyfermenticus KJS-2 (BP-KJS-2) was used to produce a lipopeptide-type surfactin. To accomplish this, a surfactin-producing BP-KJS-2 was fermented by soybeans. The surfactin was then purified by a procedure including ethanol treatment and preparative chromatography. Next, the biochemical structure of the purified surfactin was analyzed by electrospray ionization mass spectrometry (ESI-MS) and high-resolution ESI Q-Tof mass spectrometry (Q-Tof MS). In addition, the masses of the four peaks were determined to be 1007, 1021, 1035, and 1049 m/z revealing that the compound was mixture with quasi-molecular ions. Taken together, these findings indicated that the lipopeptide had a cyclic structure and amino acid composition of Gln-Leu-Leu-Leu-Val-Asp-Leu-Leu, and that the major lipopeptide product of BP-KJS-2 is the surfactin isoform. In addition, this lipopeptide showed strong antimicrobial activity against bacteria at the level of 0.05 mg/mL.

Two organic compounds with potential absorption enhancing effects, bile acids and transferrin, were examined by the gastro-intestinal (GI) absorption of therapeutic salmon calcitonin (sCT) as encapsulated by poly(lactide-co-glycolide) (PLGA) for the treatment of osteoporosis. The sCT-loaded PLGA nanocapsules were prepared by O/W emulsification approach. Either additive of a designated content was mixed with sCT dissolved in methanol. For bile acids, their content (0–7.5 mg to sCT 6 mg) was observed to have a substantial effect both on the emulsification process and the encapsulation efficiency. When 1.5 mg of bile acids was added, sCT-loaded PLGA nanocapsules of about 700 nm in diameter and with a fairly high encapsulation efficiency greater than 35% were produced. Accordingly, this formulation gave the most significant hypocalcemic effect in an in vivo experiment with SD rats. On the other hand, a too high bile acids loading resulted in a poor encapsulation efficiency of less than 7%. Two principal roles of bile acids were proposed: emulsifying agent and absorption enhancer. Transferrin, a human glycoprotein of 80 kDa molecular weight, turned out to have potential as absorption enhancer as well.

Bacillus polyfermenticus KJS-2 (Bp2) was isolated from , a commercially available probiotics consisting of more than 4 strains. The objective of this study was to investigate the effect of three-layer coating on the stabilty of Bp2. Bp2 was microencapsulated with sodium alginate using an air atomizer. The Bp2 loaded pellets were also coated with HFP-chitosan and HPMCP for oral delivery system. When compared to the uncoated Bp2, the survival of the three-layer coated Bp2 increased to approximately 63% (p and , Bp2 in coated beads was very stable (p

The aim of this study was to elucidate the antioxidant properties of fucoidan extracts (FE) against CCl(4)-induced oxidative stress by monitoring the levels of glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Female, Sparague-Dowley rats were administered with FE (100 mg/kg daily) for 14 days and CCl(4) on the 15'th day, 12 h before they were sacrificed. The levels of GOT, GPT, ALP and LDH in serum of rats, as well as the levels of MDA, SOD, CAT and GPx in total liver homogenate were analyzed. CCl(4)-treatment was found to increase the levels of GOT, GPT, ALP, LDH and MDA, as well as decrease levels of SOD, CAT and GPx significantly. The pre-treatment of rats with FE, however, suppressed the increment of levels of GOT, GPT, ALP, LDH and MDA, as well as recovered the levels of SOD, CAT and GPx in CCl(4)-treated rats. Moreover there was a significant decrease in incidences of necrosis and cirrhosis in the liver tissue of FE-treated rats. These results implied that FE possessed antioxidant properties against CCl(4)-induced oxidative stress.

Prostaglandin was formulated as two self-microemulsifying drug delivery systems (SMEDDS) composed of Cremophor or Cremophor as a surfactant, ethanol as a cosurfactant and Labrafac as an oil to develop liquid preparation for the treatment of erectile dysfunction. In pseudo-ternary phase diagram, viscous gel area and microemulsion area were defined. In the measurement of viscosity, the viscosity of two formulations increased gradually upon the addition of water and it decreased from the water contents over 40%. With excessive water, the present systems formed a microemulsion spontaneously. From these results, rte could expect that the present liquid SMEDDS formulations might stay within the urethra in the viscous state when contacting the moisture of the urethra and can be easily eliminated by urination. In long-term stability study, we could select one formulation more stable at the shelf storage condition of .

Epilepsy is a neurological disorder with recurrent unprovoked seizures as the main symptom. Of the coumarin derivatives in Angelica gigas, decursin, a major coumarin component, was reported to exhibit significant protective activity against glutamate-induced neurotoxicity when added to primary cultures of rat cortical cells. This study served to investigate the effects of decursin on a kainic acid (KA)-induced status epilepticus model. Thirty minutes after intraperitoneal injections of decursin (20 mg/kg) in male 7-week-old C57BL/6 mice, the animals were treated with KA (30 mg/kg, intraperitoneally) and then examined for behavioral seizure score, electroencephalogram, seizure-related expressed protein levels, neuronal cell loss, neurodegeneration, and astrogliosis. KA injections significantly enhanced neurodegenerative conditions but treatment with decursin 30 min before KA injection reduced the detrimental effects of KA in mice. The decursin-treated KA-injected group showed significantly decreased behavioral seizure activity and remarkably attenuated intense and high-frequency seizure discharges in the parietal cortex for 2 h compared with the group treated only with KA. Furthermore, in-vivo results indicated that decursin strongly inhibits selective neuronal death, astrogliosis, and oxidative stress induced by KA administration. Therefore decursin is able to attenuate KA-induced seizures and could have potential as an antiepileptic drug.