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Myelosuppression is a major adverse effect of chemotherapy. With the increasing number of cancer patients worldwide, there is a growing interest in therapeutic approaches that reduce the adverse effects of chemotherapy.

Purpose: To investigate the pharmacological effects of the active saponins isolated from Panax ginseng Meyer (P. ginseng) via extraction, heat treatment, and enzyme conversion. Methods: The effects of active saponins on rat blood were determined using a multichannel analyzer. The population doubling time (PDT) of mesenchymal stem cells (MSCs) and human-derived leukocyte cancer cells (A549) was determined by cell counting. b-galactosidase was measured in human toothderived stem cells (HTS) using a β-galactosidase ELISA kit. Results: Intraperitoneal administration of active saponins resulted in 30.09 % increase in red blood cell count and 55.55 % decrease in blood triglyceride concentrations. The stimulatory effect of active saponins (10 ng/mL) on cellular differentiation was determined based on PDT of MSCs, which decreased by 33.82 % compared to control. A 22.29 % increase in PDT of A549 cells demonstrated the suppressive effects of active saponins on cancer cell growth. Active saponins (10 ng/mL) also decreased intracellular β-galactosidase concentration by 20.42 % in HTS cells. Conclusion: Administration of active saponins to rats extends the lifespan, promotes differentiation in MSCs, suppresses A549 cell differentiation, and reduces TG and b-galactosidase associated with aging in HTS. Thus, active saponins have potentially beneficial effects in humans.

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

Purpose: To determine new metabolites of the main components of Angelica gigas known to give anti-inflammation and pain relief Methods: Decursinol and blank sample were metabolized in human liver microsomes. The metabolized samples were centrifuged and deproteinated by adding 3 mL acetonitrile. The acetonitrile layer was concentrated and reconstituted in methanol. Finally, the prepared sample was injected into the LC-Q- TOF-MS. Results: Four new metabolites of decursinol with m/z ranging from 263.0912 ~ 263.0920 were identified as hydroxylated forms of decursinol, and the hydroxylated position of each metabolite was characterized using TOF mass spectrum. Their error values of detected m/z were 0.38 ~ 2.29 ppm, which indicates high accuracy of analysis. Conclusion: Previously unreported decursinol metabolites have been identified in this study. The findings provide athe basis for further pharmaceutical studies and functional food development using decursinol.

Cultivated wild ginseng has a variety of pharmacological effects. The aim of this study was to investigate the effects of cultivated wild ginseng extracts (CWGE) on apoptosis. CWGE showed the ability to protect hormone production (testosterone and progesterone from in vitro results) in TM3 Leydig and TM4 Sertoli cells damaged by Bisphenol A (BPA). CWGE also showed the ability to protect production of testosterone (7.24%, P

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.

Recent studies have reported the relationship between reduced sperm counts and male infertility. The effects of cultivated wild ginseng extracts, which include ginsenosides, on cellular antioxidant activities were studied in testicular cells and animal models. In a study of rats, the weight of testis-right (15.38%, P

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.

Vardenafil, a remedy for erectile dysfunction, is easily modified, facilitating the creation of analogues that have been illegally added to functional foods and counterfeit medications. However, the medical profile of these analogues, including their safety, efficacy, safe drug combinations, metabolism and excretion, has not been completely evaluated, which could cause serious health problems. In this study, two representative vardenafil analogues, pseudovardenafil and hydroxyvardenafil, were metabolized with in-vitro model (human liver microsome) and in-vivo model (rats). The metabolized samples were extracted and characterized, using liquid chromatography quadrupole-time of flight mass spectrometry (LC-Q-TOF-MS). Some imprecise interpretations were evaluated with tandem mass spectrometry (LC-Q-TOF-MS/MS) for mass fragmentation analysis. A total of 11 metabolites of pseudovardenafil and 13 metabolites of hydroxyvardenafil that were identified have never been reported. These new metabolites could be usefully applied to forensic science and other metabolic fields. Furthermore, they could serve as principal references for the toxicity, danger, and side effects of unlawful vardenafil counterfeits.

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.

The aim of this study was to determine the effect of decursin (D) and decursinol angelate (DA) against bisphenol A (BPA) toxicity in a rat two-generation study. Adult rats were divided into the following three groups: (1) control, (2) BPA, and (3) BPA+D/DA. The D and DA treatment of F0 parents increased the terminal body weight and relative adult organ weights (testes, kidneys, spleen, and liver) when compared with the BPA group. A significant decrease in sperm count was found in the BPA+D/DA (7.69%) and BPA (64.70%, p

Biological control using the plant growth-promoting Rhizobacterium (PGPR) has received significant attention in recent years. PGPR has been linked with promoting growth in economically important crops, such as potatoes, tomatoes, and rice. Bacillus mojavensis KJS-3 (Moja-3), isolated from food waste, possesses antifungal properties against Aspergillus terreus, A. fumagatus, A. flavus, and Fusarium redolense, and it may have potential in the development of products for industrial applications. The main purpose of this study was to determine the effects of spraying the PGPR Bacillus mojavensis KJS-3 on the growth of altari radish (leaf number, leaf length, leaf weight, root length, and rhizome length, adjacent portion diameter, and weight) and lettuce (leaf number, length, width, and weight). Three different concentrations of the foliar spray treatment of B. mojavensis KJS-3 were applied to the altari radish and lettuce: the recommended standard concentration of 1×10 9 cfu/g, half the standard concentration of 0.5×10 9 cfu/g, and double the standard concentration of 2×10 9 cfu/g). The B. mojavensis strain foliar spray treatment increased the growth of the leaves and roots of the altari radish and increased the growth of the lettuce leaves. For both plants, the recommended concentration of B. mojavensis KJS-3 produced better growth than half the standard concentration, and the growth was similar with the double dose. This study demonstrates positive effects of Moja-3, suggesting it may be a potential new bio-fertilizer for improving the growth of altari radish and lettuce.

The aim of this study was to investigate the positive effects of decursin and decursinol angelate (D/DA) on the reproductive system of male rats as well as to examine whether D/DA is able to ameliorate the effects of bisphenol A (BPA). Adult rats were divided into the following four groups: (1) control, (2) BPA, (3) D/DA, and (4) BPA+D/DA. Organ weight ratio of vital organs decreased in the kidney (9.5%) and increased in the prostate (24.07%) and epididymis (22.14%) in the BPA+D/DA group compared to the values in the BPA group. A significant decrease (P

The genotoxicity of crude substances cultured in Bacillus mojavensis KJS-3 (B. mojavensis KJS-3) was investigated by using Ames tester strains of Salmonella typhimurium (S. typhimurium) with or without metabolic activation (S9 mix). No increase in the number of revertants was observed in response to any of the doses of the culture supernatant fermented by B. mojavensis KJS-3 (5, 10, 50, 100, and 500 μg/plate) in S. typhimurium TA 98, 100, 1535 and 1537 both in the absence and in the presence of S-9 metabolic activation system. The half-maximal inhibitory concentration (IC50) value of the culture supernatant was >83.33 μg/mL. Crude substances had no effect on the DNA repair system for mutagenesis. Furthermore, the cell number of S. typhimurium strains was observed to have decreased compared to the solvent control. These results showed dose-dependent activity on the mutagenicity of crude substances in Ames test. These results strongly indicate that antimutagenic compounds are produced during fermentation by B. mojavensis KJS-3. On using the Chinese hamster lung cell line in mammalian cell system, no clastogenicity of the culture supernatant fermented by B. mojavensis KJS-3 was observed in the absence or presence of the S9 mix at the concentrations of 1.66, 8.33, 16.67, and 83.33 μg/mL. No significant increase in chromosome aberrations was observed in response to treatment with any of these concentrations, regardless of activation of the metabolic system. Consequently, the mutagenic potential of the culture supernatant was not induced with respect to in vitro bacterial reverse mutation and clastogenicity in the range of concentrations evaluated in these experiments in our study.

The identification and characterization of Bacillus mojavensis KJS-3 was performed by in vitro tests. A 16S rDNA sequence and phylogenetic tree demonstrated that this isolate belongs to the B. mojavensis group. B. mojavensis KJS-3 supplies nutrients by synthesizing several vitamins. B. mojavensis KJS-3 produces α-amylase and protease. B. mojavensis KJS-3 is cultured well under aerobic conditions without gas production. B. mojavensis KJS-3 allows for assimilation of cholesterol and bile salt hydrolase activity. Finally, adhesion experiments using Caco-2 cells revealed that the adherence of B. mojavensis KJS-3 to Caco-2 cells was approximately 51.2±8.14%.

The aim of the present study was to improve the solubility and bioavailability of a poorly water-soluble drug in human body, using a solid dispersion technique (hot melt extrusion). The solid dispersion was prepared by cooling the hot melt of the drug in the carrier (Vitamin E TPGS and PVP). The dissolution rate of formulation 1 from a novel formulation prepared by solid dispersion technique was equal to release of formulation 6 (40% of eprosartan mesylate is in contrast to teveten) within 60 min (Table 1). The oral bioavailability of new eprosartan mesylate tablet having vitamin E TPGS and PVP K29 was tested on rats and dogs. Of the absorption enhancer and polymer tested, vitamin E TPGS and PVP K29, resulted in the greatest increases of AUC in animals (about 2.5-fold increase in rat and dog). When eprosartan mesylate was mixed with the absorption enhancer and polymer in a ratio of 2.94:2:1, vitamin E TPGS and PVP K29 improved eprosartan mesylate bioavailability significantly compared with the conventional immediate release (IR) tablet Teveten (formulation 7). These results show that solid dispersion using vitamin E TPGS and PVP K29 is a promising approach for developing eprosartan mesylate drug products.

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.

The principal objective of this study was to evaluate the antibacterial activities of macrolactin A (MA) and 7-O-succinyl macrolactin A (SMA) generated from Bacillus polyfermenticus KJS-2 against vancomycin-resistant enterococci (VREs) and methicillin-resistant Staphylococcus aureus. The minimal inhibitory concentrations (MICs) of MA and SMA against VREs were 16 and 2∼1 μg/mL, respectively, and the MICs of MA and SMA against methicillin-resistant Staphylococcus aureus were 2 and < 0.25 μg/mL, respectively. Their MIC values were comparable or superior to those of teicoplanin. In evaluating the inhibitory effects of intestinal VRE colonization in mice, the oral MA and SMA effected a rapid inhibition of intestinal VRE colonization in mice, and the intraperitoneal SMA also inhibited VRE colonization, whereas intraperitoneal MA did not.

In this study, we isolated five macrolactin compounds from a fermentation broth of Bacillus polyfermenticus KJS-2. The macrolactin compounds were structurally identified as macrolactin A (MA), 7-O-malonyl macrolactin A (MMA), 7-O-succinyl macrolactin A (SMA), macrolactin E (ME) and macrolactin F (MF) via a variety of NMR techniques, COZY, DEPT, HMQC and HMBC, and mass and specific rotation assays. The three macrolactin compounds, MA, MMA and SMA, profoundly inhibited the growth of both vancomycin-resistant Enterococci (VREs) and methicillin-resistant Staphylococcus aureus (MRSA), the inhibition of which were estimated via a disc agar diffusion bioassay. MA, MMA, and SMA exhibited antibacterial activities superior to those of vancomycin and teicoplanin.

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%.

Lyophilized powder (BP2FS) of soybeans fermented with Bacillus polyfermenticus KJS-2 (B. polyfermenticus KJS-2) exhibited in vitro antibacterial activities against eight pathogenic bacteria. BP2FS was used as a fodder additive for Oplegnathus fasciatus (O. fasciatus) culture. One group (UFD) of O. fasciatus was fed a commercial fodder, while another group (FD) was fed the same fodder, but including BP2FS (6×10⁴ cfu g?¹ fodder), two times daily for 120 days. The mean body weight of the FD group (67.29±12.62 g) was higher than that of the UFD group (56.56±8.21 g) after 120 days. The survival rate of FD was 80% compared to 40% for the UFD group. Cumulative mortalities in the FD and UFD groups were 18.95% and 60.98% respectively. B. polyfermenticus KJS-2 was isolated from the intestines of the FD group and the number of viable colonies was estimated to be 1.04×10⁴ cfu g?¹. Iridovirus and Vibrio vulnificus was detected in the organs of the UFD group but not in the FD group. All of the infected fish showed typical clinical symptoms of hemorrhage in their tail fins. Dissection of the infected internal organs revealed liver congestion and spleen enlargement - typical symptoms caused by iridovirus infection. These results clearly show that BP2FS is highly beneficial in preventing O. fasciatus from iridovirus infection.

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.

Macrolactin A (MA) and 7- O -succinyl macrolactin A (SMA), polyene macrolides containing a 24-membered lactone ring, show antibiotic effects superior to those of teicoplanin against vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus . MA and SMA are currently being evaluated as antitumor agents in preclinical studies in Korea. We evaluated the potential of MA and SMA for the inhibition or induction of human liver cytochrome P450 (CYP) enzymes and UDP-glucuronosyltransferases (UGTs) in vitro to assess their safety as new molecular entities. We demonstrated that MA and SMA are potent competitive inhibitors of CYP2C9, with K i values of 4.06 μM and 10.6 μM, respectively. MA and SMA also weakly inhibited UGT1A1 activity, with K i values of 40.1 μM and 65.3 μM, respectively. However, these macrolactins showed no time-dependent inactivation of the nine CYPs studied. In addition, MA and SMA did not induce CYP1A2, CYP2B6, or CYP3A4/5. On the basis of an in vitro-in vivo extrapolation, our data strongly suggested that MA and SMA are unlikely to cause clinically significant drug-drug interactions mediated via inhibition or induction of most of the CYPs involved in drug metabolism in vivo , except for the inhibition of CYP2C9 by MA. Similarly, MA and SMA are unlikely to inhibit the activity of UGT1A1, UGT1A4, UGT1A6, UGT1A9, and UGT2B7 enzymes in vivo . Although further investigations will be required to clarify the in vivo interactions of MA with CYP2C9-targeted drugs, our findings offer a clearer understanding and prediction of drug-drug interactions for the safe use of MA and SMA in clinical practice.

Decursin, a coumarin compound, was originally isolated from the roots of Angelica gigas almost four decades ago, and it was found to exhibit cytotoxicity against various types of human cancer cells and anti-amnesic activity in vivo through the inhibition of AChE activity. However, the anti-skin photoaging effects of decursin have not been reported to date. In the present study, we investigated the inhibitory effects of decursin on the expression of matrix metalloproteinase (MMP)-1 and MMP-3 in human dermal fibroblast (HDF) cells. Western blot analysis and real-time PCR revealed that decursin inhibited the ultraviolet (UV)B-induced expression of MMP-1 and MMP-3 in a dose-dependent manner. Decursin significantly blocked the UVB-induced activation of nuclear factor-κB (NF-κB). However, decursin showed no effect on MAPK or AP-1 activity. In this study, decursin prevented the UVB-induced expression of MMPs via the inhibition of NF-κB activation. In conclusion, decursin may be a potential agent for the prevention and treatment of skin photoaging.

A simple, sensitive and reproducible isocratic reversed-phase (C18) high-performance liquid chromatography (HPLC) method was developed to determine 7-O-succinyl macrolactin A (SMA) in rat plasma and urine samples using UV detector set at 230 nm. Lamotrigine was used as internal standards (IS) to ensure the precision and accuracy of the method. The retention times of SMA and IS for the plasma sample were 9.2 and 4.4 min, respectively, and those for the urine samples were 7.9 and 4.3 min, respectively. The intra- and inter-day variations of the analytical responses, expressed in terms of relative standard deviation, were less than 14.9%. The accuracy, in terms of average analytical recovery, ranged from 90.4 to 119%. The lower limits of quantification of SMA in rat plasma and urine samples were 0.02 and 0.1 µg/mL, respectively. This method is applicable for the pharmacokinetic studies of SMA in rats. Copyright © 2012 John Wiley & Sons, Ltd.

A simple, sensitive and reproducible isocratic reversed-phase (C(18) ) high-performance liquid chromatography (HPLC) method was developed to determine 7-O-succinyl macrolactin A (SMA) in rat plasma and urine samples using UV detector set at 230 nm. Lamotrigine was used as internal standards (IS) to ensure the precision and accuracy of the method. The retention times of SMA and IS for the plasma sample were 9.2 and 4.4 min, respectively, and those for the urine samples were 7.9 and 4.3 min, respectively. The intra- and inter-day variations of the analytical responses, expressed in terms of relative standard deviation, were less than 14.9%. The accuracy, in terms of average analytical recovery, ranged from 90.4 to 119%. The lower limits of quantification of SMA in rat plasma and urine samples were 0.02 and 0.1 µg/mL, respectively. This method is applicable for the pharmacokinetic studies of SMA in rats.

Aim: To evaluate the efficacy and safety of a newly developed formulation of phentermine diffuse-controlled release (DCR) in patients with obesity. Methods: This was a randomized, double-blind, placebo-controlled trial of 12 weeks of treatment with phentermine DCR 30 mg (n = 37) or placebo (n = 37), administered once daily in patients with obesity with controlled diabetes, hypertension or dyslipidaemia. The efficacy was evaluated by changes in body weight and waist circumference from baseline at 12 weeks and also changes in metabolic parameters, including lipid profiles and blood pressure. Results: The participants in the phentermine DCR group showed significant reductions in body weight (−8.1 ± 3.9 vs. −1.7 ± 2.9 kg, p < 0.001) and waist circumference (7.2 ± 0.5 vs. 2.1 ± 0.6 cm, p < 0.001) compared with those in the placebo group. Weight reductions of 5% or greater from the baseline (95.8 vs. 20.8%, p < 0.001) and 10% or more (62.5 vs. 4.7%, p < 0.001) were achieved in the DCR phentermine group and placebo group, respectively. Total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels were significantly improved in the phentermine DCR group. However, there were no significant differences in systolic and diastolic blood pressure between the groups. Dry mouth and insomnia were the most common adverse events, but these were mild to moderate and transient. Conclusions: Short-term phentermine DCR treatment resulted in significant reduction in weight and improvement of metabolic parameters, including waist circumference and some lipid profiles, without clinically severe adverse events. Further study is needed to show long-term efficacy and safety of phentermine DCR in Korean patients with obesity.

The pharmacokinetics of decursin and decursinol angelate (D/DA) was investigated in male SD rats following oral and intravenous administration. D/DA and metabolites obtained from in vitro samples were evaluated by LC/MS. The level of D/DA and metabolized decursinol in the blood following oral and intravenous administration declined according to first-order kinetics, with T1/2 values of 56.67, 58.01 and 57.22 h, respectively, being observed after administration of a dose of 2 mg/kg body weight. The large intestine was the major site of disposition following oral administration. These data indicate that D/DA is rapidly absorbed from the gastrointestinal tract. In in vitro experiment utilizing liver microsomal protein, the major metabolic reaction of D/DA occurred to change decursinol. The cumulative biliary, urinary, and fecal excretion of D/DA in bile duct-cannulated rats was 36.10+/-2.9, 25.35+/-3.8, and 34.20+/-3.2%, respectively, at 72 h after administration. These results indicate that the absorption of D/DA is almost complete, and that its metabolites are primarily excreted into feces through the bile. These results indicate that D/DA is subject to enterohepatic circulation.