The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
/
v.15
no.2
/
pp.33-52
/
2002
The effects of Arctii fructus extract on allegenic inflammation were investigated using in vivo and in vitro test models. Firstly, the cytotoxicity of Arctii fructus extract was validated using MTT assay. As a result, Arctii fructus extract showed no cytotoxic potential, while SDS, a positive control, revealed strong cytotoxic effect. In LLNA assay, Arctii fructus extract showed no skin allergenicity. Next, the anti-allergic actions of Arctii fructus extract were evaluated using rodent experimental models. The oral, intraperitoneal and intradermal administration of Arctii fructus extract significantly inhibited the compound 48/80-induced vascular permeability documented by Evans blue extravasation. In addition, Arctii fructus extract showed potent inhibitory effect on passive cutaneous anaphylaxis activated by anti-dinitrophenyl (DNP) IgE when orally administered. In an in vitro study, Arctii fructus extract revealed to possess inhibitory potential on the compound 48/80-induced histamine release from rat peritoneal mast cells. Moreover, Arctii fructus extract inhibited the IL-4 and TNF-${\alpha}$ mRNA induction by PMA and A23187 in human leukemia mast cells, HMC-1. Finally, it revealed that Arctii fructus extract significantly suppressed histamin-provoked antigenic inflammation reactions in human prick test. Taken together, these results suggest that anti-allergic action of Arctii fructus extract may be due to the inhibition of histamine release and cytokine gene expression in the mast cells.
Wijesinghe, W.A.J.P.;Kang, Min-Cheol;Lee, Won-Woo;Lee, Hyi-Seung;Kamada, Takashi;Vairappan, Charles S.;Jeon, You-Jin
ALGAE
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v.29
no.4
/
pp.333-341
/
2014
In this study, four compounds isolated from the red alga Laurencia snackeyi were evaluated for their potential anti-inflammatory effect in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. These compounds were tested for their inhibitory effects on nitric oxide (NO) production in LPS-stimulated RAW 264.7 cells. Since $5{\beta}$-hydroxypalisadin B showed the best activity it was further tested for the production of prostaglandin-$E_2$ ($PGE_2$), expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), the release of pro-inflammatory cytokines tumor necrotic factor-alpha (TNF-${\alpha}$), interleukin-$1{\beta}$ (IL-$1{\beta}$), and interleukin-6 (IL-6). $5{\beta}$-Hydroxypalisadin B significantly reduced the $PGE_2$ release and suppressed the iNOS and COX-2 expression in LPS-stimulated RAW 264.7 cells. It also significantly reduced the release of pro-inflammatory cytokines TNF-${\alpha}$, IL-$1{\beta}$, and IL-6. These findings provide the first evidence of anti-inflammatory potential of $5{\beta}$-hydroxypalisadin B isolated from the red alga L. snackeyi and hence, it could be exploited as an active ingredient in pharmaceutical, nutraceutical and functional food applications.
Journal of Physiology & Pathology in Korean Medicine
/
v.23
no.4
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pp.888-894
/
2009
It has been reported that silibinin, a natural polyphenolic flavonoid, induces cell death in various cancer cell types. However, the underlying mechanisms by which silibinin induces apoptosis in human glioma cells are poorly understood. The present study was therefore undertaken to examine the effect of silibinin on glioma cell apoptosis and to determine its underlying mechanism in human glioma cells. Apoptosis was estimated by FACS analysis. Reactive oxygen species (ROS) generation and mitochondrial membrane potential (${\Psi}m$) were measured using fluorescence dyes DCFH-DA and $DiOC_6$(3), respectively. Cytochrome c release from mitochondria and caspase-3 activation were estimated by Western blot analysis using specific antibodies. Exposure of cells to 30 mM silibinin induced apoptosis starting at 6 h, with increasing effects after 12-48h in a time-dependent manner. Silibinin caused ROS generation and disruption of ym, which were associated with the silibinin-induced apoptosis. The silibinin-induced ROS generation and disruption in ym were prevented by inhibitors of mitochondrial electron transport chain. The hydrogen peroxide scavenger catalase blocked ROS generation and apoptosis induced by silibinin. Silibinin induced cytochrome c release into cytosolic fraction and its effect was prevented by catalase and cyclosporine A. Silibinin treatment caused caspase-3 activation, which was inhibited by DVED-CHO and cyclosporine A. Pretreatment of caspase inhibitors also protected against the silibinin-induced apoptosis. These findings indicate that ROS generation plays a critical role in the initiation of the silibinin-induced apoptotic cascade by mediation of the mitochondrial apoptotic pathway including the disruption of ${\Psi}m$, cytochrome c release, and caspase-3 activation.
Kim Dae-Keun;Park Seung-Chun;Kim Tae-Wan;Lee Keun-Woo;Oh Tae-Ho
Journal of Veterinary Clinics
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v.22
no.3
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pp.175-180
/
2005
The purpose of this study is to investigate the effects of formulation variables on the release of cefadroxil form chitosan beads, to optimize the preparation of chitosan beads loaded with the drug for controlled release, and to evaluate the drug release form chitosan beads in dogs. Chitosan beads were prepared with tripolyphosphate (TPP) by ionic cross-linking and those sizes were less than 1 mm in diameter. The release behaviour of cefadroxil was affected various factors. As pH of TPP solutions decreased, the entrapment efficiency of cefadroxil increased, whereas the release of cefadroxil decreased. The release rate of cefadroxil form chitosan beads decreaed with the increased TPP solution concentration. When cross-linking time increased, the release of the drug from chitosan beads decreased. The cefadroxil loaded beads were implanted to 4 mixed breed dogs. The concentration of cefadroxil in sera due to chitosan beads implanted with 50 mg/kg body weight of beads was sustained more than 1 ug/ml for the whole 7 days period. Therefore, the cefadroxil loaded beads can be used successfully in pyoderma of dogs. These results indicate that chitosan beads may become a potential delivery system to control the release of drug.
Lee, Sang-Kook;Minner, David D.;Christians, Nick E.
Asian Journal of Turfgrass Science
/
v.24
no.2
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pp.145-148
/
2010
Nitrogen (N) is one of the most important nutrients among 17 essential nutrients for maintaining turfgrass color and quality. The slow release fertilizers were initially developed to provide a more consistent release of nitrogen over a longer period and are often used to decrease leaching potential from sandy soils. The goal of this study is to determine if various slow release N sources affect the rate at which turfgrass establishes. Six nitrogen sources were evaluated; Nitroform (38-0-0), Nutralene (40-0-0), Organiform (30-0-0), Sulfur coated urea (SCU, 37-0-0), urea (46-0- 0), and Milorganite (6-0-0). The root zone media was seeded and sodded with 'Limousine' Kentucky bluegrass (Poa pratensis L.). Sodded pots produced 182 to 518 g more clipping dry weight than seeded pots. Among seeded pots, Milorganite produced greater amount of root dry weight than any other N sources. Because the period of turfgrass growth is different between sodded and seeded plots, there were differences on clipping yield and root growth. Overall, high N rate had turf color greater than acceptable color of 6 among seeded pots throughout the study. However, low N rate didn't produce acceptable turf color throughout the study. Based on the result of this tudy, ilorganite would be ecommended for new establishment of Kentucky bluegrass an urea with less clipping yield which can lead to reduce abor.
The increase in P availability to rice under flooded soil conditions involves the reductive dissolution of iron phosphate and iron (hydr)oxide phosphate. However, since $NO_3^-$ is a more favourable electron acceptor in anaerobic soils than Fe, high$NO_3^-$ loads function as a redox buffer limiting the reduction of Fe. The effect of adding $NO_3^-$ on Fe reduction and P release in paddy soil was investigated. Pot experiment was conducted where $NO_3^-$ was added to flooded soil and changes of redox potential and $Fe_2^+$, $NO_3^-$ and $PO_4^{3-}$ concentrations in soil solution at 10 cm depth were monitored as a function of time. Redox potential decreased with time to -96 mV, but it was temporarily poised at about 330${\sim}$360 mV when $NO_3^-$ was present. Nitrate addition to soil led to reduced release of $Fe_2^+$ and prevented the solubilization of P. Phosphate in pore water began to rise soon after incubation and reached final concentrations about 0.82 mg P/L in the soil without $NO_3^-$ addition. But, in the soil with $NO_3^-$ addition, $PO_4^{3-}$ in pore water was maintained in the range of 0.2${\sim}$0.3 mg P/L. The duration of inhibition in $Fe_2^+$ release was closely related to the presence of $NO_3^-$, and the timing of $PO_4^{3-}$ release was inversely related to the $NO_3^-$ concentration in soil solution. The results suggest that preferential use of $NO_3^-$ as an electron acceptor in anaerobic soil condition can strongly limit Fe reduction and P solubilization.
The objective of this study was to provide a better understanding of SUPAC-IR and its application in handling postapproval changes to immediate release solid oral dosage forms. Originally, SUPAC-IR was aimed at reducing the regulator burdern of the industry when they were making postapproval changes, but still at maintaining the formulation quality and performance of a drug product. The postapproval changes that were covered under SUPAC-IR included variations in the components ad composition of formulation, the site of manufacturing, batch size, manufacturing equipment, and manufacturing process. The guidance defined levels of changes, based on the likelihood of risk ocurrence and potential impact of postapproval changes upon the safety and efficacy of a drug product I suggested what a type of fing report should be submitted to the FDA for each level of change. Chemist, manufacturing, and control tests to be executed were also recommended for each change level The important tests specified in the guidance included batch release, stability, in vitro dissolution, and in vivo bioequivalence tests. However, there have been strong demands on revising the current SUPAC-IR in order to resolve some issues and to improve its usefulness in evaluating postapproval changes to immediate release solid oral dosage forms. In particular, the rigorous requirement of case C dissolution test and the definition of batch size were challenged by both academia and the industry. A revision work was in progress to reflect these inputs and to expand the utility of SUPAC-IR. As a result of these concerted efforts, an updated 2nd version of SPAC-IR would be likely to be issued ver soon to the public.
Biodegradable poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles were developed for sustained delivery of water-soluble macromolecules. PLGA nanoparticles were fabricated by spontaneous emulsification solvent diffusion method generating negatively charged particles and heterogeneous size distribution. As a model drug, blue dextran was encapsulated in PLGA nanoparticles. In addition, nanoparticles were also prepared with varying ratio of poloxamer 188 (P188) and poloxamer 407 (P407), and coating with poly(vinyl alcohol) (PVA). Then, the particle size, zeta potential and encapsulation efficiency of nanoparticles containing blue dextran were studied. In vitro release of blue dextran from nanoparticles was also investigated. The surface and morphology of nanoparticles were characterized by scanning electron microscopy (SEM). In case of nanoparticles prepared with PLGA, P407, and different organic solvents, particle size was in the range of $230{\sim}320\;nm$ and zeta potentials of nanoparticles were negative. The SEM images showed that ethyl acetate is suitable for the formulation of PLGA nanoparticles with good appearance. Moreover, ethyl acetate showed higher encapsulation efficiency than other solvents. The addition of P188 to formulation did not affect the particle size of PLGA nanoparticles but altered the release patterns of blue dextran from nanoparticles. However, PVA, as a coating material, altered the particle size with increasing the PVA concentration. The nanoparticles were physically stable in the change of particle size during long-term storage. From the results, the PLGA nanoparticles prepared with various contents of poloxamers and PVA, could modulate the particles size of nanoparticles, in vitro release pattern, and encapsulation of water-soluble macromolecules.
Although oral route is the most convenient route for drug administration, the short and variable transit of drug through GI tract restricts the sustained drug absorption after oral administration. Thus, for sustained absorption of drugs, it is desirable to prolong the GI transit time by retaining the dosage forms in the stomach. In this study, the enzyme-digestible swelling hydrogel was synthesized by heating the mixed solution of N-vinyl-2-pyrrolidone[monomer], acrylated albumin[crosslinking agent] and proxyphylline[drug] at $65^{\circ}C$ for 10 hours in the cylindrical test tube. The resultant hydrogel tablet (diameter; 0.77 cm, thickness; 0.47 cm) was designed to swell in the gastric fluid after oral administration to such a size that passing through the pylorus could be inhibited during the drug release. After releasing drug, the hydrogel was expected to be degraded by pepsin, an enzyme in the stomach, and eventually solubilized. Actually, the hydrogel synthesized in the study swelled to a size larger than the diameter of the pylorus ($1.3{\pm}0.7$ cm) and slowly digested in the presence of pepsin. Drug release from the hydrogel was prolonged up to about 12 hours. The swelling kinetics was dependent on albumin acrylation time, drug content and gel thickness. Particularly the gel thickness was the most important factor that influences on drug release. By adjusting these factors, the albumin-crosslinked hydrogel was expected to be retained in the stomach for up to 60 hours and used as a potential platform of drugs for long-term GI absorption.
Biotransformation of pharmacologically inactive lactone prodrug simvastatin (SV) into pharmacologically active simvastatin ${\beta}$-hydroxy acid (SVA) exhibits inter-species differences due to variations in amount and activity of esterase enzymes. In this study, we investigated the pharmacokinetics (PK) of SV and its metabolite SVA following oral doses of SV from controlled-release (CR) tablets and immediate-release (IR) tablets in rodent and canine animal models that features different esterase activity. In rat PK study, no SV was detected in plasma for both formulations due to rapid hydrolysis of SV into SVA by plasma esterase. Besides, no significant differences in PK parameters of SV or SVA were observed between both species. In dog PK study, the relative oral bioavailability of CR tablets in terms of SV was 72.3% compared to IR tablets. Regarding formulation differences in dogs, CR tablets exhibited significantly lower $C_{max}$ (p<0.05), and higher $T_{max}$ (p<0.01) and MRT (p<0.01) for both SV and SVA compared to IR tablets. Accordingly, CR tablets of SV with prolonged drug release profiles in both species might be a potential candidate for a more effective delivery of SV with reduced side effects. Besides, similar PK parameters of SV and SVA in both species despite variation in enzyme activities suggested involvement of equally potent biotransformation pathways in these animal species.
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