OBJECTIVECarica papaya is an important fruit with its seeds used in the treatment of ulcer in Nigeria. This study investigated the anti-ulcerogenic and antioxidant activities of aqueous extract of Carica papaya seed against indomethacin-induced peptic ulcer in male rats.

METHODSThirty male rats were separated into 6 groups (A-F) of five rats each. For 14 d before ulcer induction with indomethacin, groups received once daily oral doses of vehicle (distilled water), cimetidine 200 mg/kg body weight (BW), or aqueous extract of C. papaya seed at doses of 100, 150 or 200 mg/kg BW (groups A, B, C, D, E and F, respectively). Twenty-four hours after the last treatment, groups B, C, D, E and F were treated with 100 mg/kg BW of indomethacin to induce ulcer formation.

RESULTSCarica papaya seed extract significantly (P< 0.05) increased gastric pH and percentage of ulcer inhibition relative to indomethacin-induced ulcer rats. The extract significantly (P< 0.05) decreased gastric acidity, gastric acid output, gastric pepsin secretion, ulcer index and gastric secretion volume relative to group B. These results were similar to that achieved by pretreatment with cimetidine. Specific activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase in the extract-treated groups (D, E and F) were increased significantly over the group B (P< 0.05). Pretreatment with the seed extract protected rats from the indomethacin-mediated decrease in enzyme function experienced by the group B. Similarly, indomethacin-mediated decrease in reduced glutathione level and indomethacin-mediated increase in malondialdehyde were reversed by Carica papaya extract.

CONCLUSIONIn this study, pretreatment with aqueous extract of Carica papaya seed exhibited anti-ulcerogenic and antioxidant effects, which may be due to the enhanced antioxidant enzymes.

Animals ; Anti-Ulcer Agents ; administration & dosage ; Carica ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Duodenal Ulcer ; chemically induced ; diagnosis ; drug therapy ; Gastric Acidity Determination ; Indomethacin ; pharmacology ; Male ; Peptic Ulcer ; chemically induced ; diagnosis ; drug therapy ; Plant Extracts ; administration & dosage ; Rats ; Seeds ; Stomach Ulcer ; chemically induced ; diagnosis ; drug therapy ; Treatment Outcome

Hydroxypropyl methylcellulose (HPMC) propels self-emulsifying drug delivery systems (SEDDS) to achieve the supersaturated state in gastrointestinal tract, which possesses important significance to enhance oral absorption for poorly water-soluble drugs. This study investigated capacities and mechanisms of HPMC with different viscosities (K4M, K15M and K100M) to inhibit drug precipitation of SEDDS in the simulated gastrointestinal tract environment in vitro. The results showed that HPMC inhibited drug precipitation during the dispersion of SEDDS under gastric conditions by inhibiting the formation of crystal nucleus and the growth of crystals. HPMC had evident effects on the rate of SEDDS lipolysis and benefited the distribution of drug molecules across into the aqueous phase and the decrease of drug sediment. The mechanisms were related to the formed network of HPMC and its viscosities and molecular weight. These results offered a reference for selecting appropriate type of HPMC as the precipitation inhibitor of supersaturatable SEDDS.
Caprylates ; chemistry ; Chemical Precipitation ; drug effects ; Crystallization ; Drug Delivery Systems ; methods ; Emulsifying Agents ; chemistry ; Emulsions ; Ethylene Glycols ; chemistry ; Glycerides ; chemistry ; Hypromellose Derivatives ; administration & dosage ; chemistry ; pharmacology ; Indomethacin ; administration & dosage ; chemistry ; Lipolysis ; drug effects ; Molecular Weight ; Polyethylene Glycols ; chemistry ; Viscosity

Ductus Arteriosus ; surgery ; Ductus Arteriosus, Patent ; drug therapy ; therapy ; Humans ; Ibuprofen ; administration & dosage ; therapeutic use ; Indomethacin ; administration & dosage ; therapeutic use ; Infant, Low Birth Weight ; Infant, Newborn ; Infant, Premature ; Infant, Premature, Diseases ; drug therapy ; surgery ; therapy ; Ligation ; methods ; Treatment Outcome

Anti-inflammatory effects of Houttuynia cordata supercritical extract (HSE) were investigated in rat carrageenan-air pouch model. Oral administration of HSE (50-200 mg/kg) suppressed carrageenan-induced exudation and albumin leakage, as well as inflammatory cell infiltration at a high dose (200 mg/kg). Intraperitoneal injection of dexamethasone (2 mg/kg) only decreased exudation and cell infiltration, while indomethacin (2 mg/kg, i.p.) reduced exudate volume and albumin content without influence on the cell number. HSE lowered tumor-necrosis factor-alpha (TNF-alpha) and nitric oxide (NO), as well as prostaglandin E2 (PGE2). Dexamethasone only reduced TNF-alpha and NO, while indomethacin decreased PGE2. The results indicate that HSE exhibits anti-inflammatory effects by inhibiting both TNF-alpha-NO and cyclooxygenase-2-PGE2 pathways.
Administration, Oral ; Animals ; Carrageenan ; Cell Count ; Dexamethasone ; Dinoprostone ; Exudates and Transudates ; Houttuynia ; Indomethacin ; Inflammation ; Injections, Intraperitoneal ; Nitric Oxide ; Rats ; Tumor Necrosis Factor-alpha

We investigated inhibitory effects of extract containing quercetin-3-O-beta-D-glucuronopyranoside (ECQ) extracted from Rumex Aquaticus Herba on indomethacin-induced gastric damage in Rats. Gastritis was induced in male Sprague-Dawley rats (200~220 g) by oral administration of indomethacin at a dose of 40 mg/kg. One hour before administration of indomethacin, animals were orally pretreated with ECQ at doses of 0.3, 1, 3 or 10 mg/kg. Six hours after indomethacin administration, the rats were sacrificed and the stomach was excised and opened along the greater curvature, and the surface area of gastric lesion was measured using optical microscope. Superoxide dismutase (SOD), catalase (CAT), myeloperoxidase (MPO) activities and malondialdehyde (MDA) levels were measured by ELISA. Western blot analysis was performed to detect protein expression of SOD-2. Linear hemorrhagic mucosal lesions were observed in the stomach 6 hours after oral administration of indomethacin. Pretreatment with ECQ significantly reduced the severity of the lesions in a dose-dependent manner. It also inhibited the reductions in SOD and CAT activities and SOD expression by the indomethacin-induced gastric damage. In addition, the pretreatment with ECQ significantly suppressed the elevation of the MPO activity and the MDA levels induced by indomethacin. These results suggest that ECQ has the inhibitory effects via antioxidative action against indomethacin-induced gastritis in rats.
Administration, Oral ; Animals ; Blotting, Western ; Catalase ; Cats ; Enzyme-Linked Immunosorbent Assay ; Gastritis ; Humans ; Indomethacin ; Male ; Malondialdehyde ; Peroxidase ; Quercetin ; Rats ; Rats, Sprague-Dawley ; Rumex ; Stomach ; Superoxide Dismutase

This paper report the development of a new dosage form - self-microemulsifying mouth dissolving films, which can improve the oral bioavailability of water insoluble drugs and have good compliance. A three factor, three-level Box-Behnken design was used for optimizing formulation, investigated the effect of amounts of microcrystalline cellulose, low-substituted hydroxypropyl cellulose and hypromellose on the weight, disintegration time, cumulative release of indomethacin after 2 min, microemulsified particle size and stretchability. Optimized self-microemulsifying mouth dissolving films could fast disintegrate in (17.09 +/- 0.72) s; obtain microemulsified particle size at (28.81 +/- 3.26) nm; and release in vitro at 2 min to (66.18 +/- 1.94)%. Self-microemulsifying mouth dissolving films with broad application prospects have good compliance, strong tensile and can be released rapidly in the mouth through fast self-microemulsifying.
Administration, Oral ; Biological Availability ; Cellulose ; analogs & derivatives ; chemistry ; Drug Compounding ; methods ; Drug Delivery Systems ; methods ; Emulsifying Agents ; chemistry ; Emulsions ; Hypromellose Derivatives ; Indomethacin ; administration & dosage ; Methylcellulose ; analogs & derivatives ; chemistry ; Particle Size ; Solubility ; Surface Properties ; Tensile Strength

Solid carriers had important effects on the properties of solid self-microemulsifying drug delivery systems (S-SMEDDS). In order to make the basis for further development of S-SMEDDS, the influences of silica on the absorption of S-SMEDDS were investigated. An in vitro lipolysis model was used to evaluate the influence of silica on self-microemulsifying drug delivery system digestion from intestinal tract. S-SMEDDS containing silica were prepared by extrusion/spheronization. The drug release and absorption were investigated. The results showed that lipolysis rate and drug concentration in aqueous phase after intestinal lipolysis both increased by adding silica, which was benefit to drug absorption. And silica was not benefit to absorption for slowing drug release. Consistently, there was no significant influence of silica on intestinal absorption. This study implied that the influences of silica on lipolysis rate and drug release were both amount dependent and it is suggested that silica could be used as the solid carrier but the proportion needs to be optimized.
Animals ; Biological Availability ; Drug Delivery Systems ; methods ; Emulsions ; Indomethacin ; administration & dosage ; pharmacokinetics ; Intestinal Absorption ; Lipolysis ; Rats ; Rats, Sprague-Dawley ; Silicon Dioxide ; administration & dosage ; chemistry ; Solubility

In this study, indomethacin (IND) loaded solidified-polymeric micelles (IND-SPM) were prepared. Their in vitro characteristics were investigated. Methoxy-poly(ethylene glycol) poly(D, L-lactide) copolymer (mPEG-PDLLA) was used as IND carrier. The preparation of IND-SPM was conducted by solution-absorption method and evaporation by rotary evaporator. Polyplasdone XL-10 was used as adsorbent. The solution-absorption method was conducted by the following procedure; IND and mPEG-PDLLA were dissolved in acetone, followed by addition of polyplasdone XL-10 and stirred to obtain a suspension. The powder of IND-SPM was simply obtained after the organic solvent was completely evaporated. More than 90% (w/w) of IND (20 mg) in the powder was dissolved in 250 mL PBS within 30 min. DSC, 1H NMR and SEM results proved that IND was encapsulated within mPEG-PDLLA. The solubility of IND in the system increased 4.6 times with the highest amount of copolymer. The solidified particles were found to be suitable for the formulation of tablets or capsules.
Administration, Oral ; Anti-Inflammatory Agents, Non-Steroidal ; administration & dosage ; chemistry ; Drug Carriers ; chemistry ; Drug Compounding ; Drug Delivery Systems ; Indomethacin ; administration & dosage ; chemistry ; Micelles ; Polyesters ; chemistry ; Polyethylene Glycols ; chemistry ; Povidone ; chemistry ; Solubility

BACKGROUND: The intravenous administration of indigo carmine has been reported to produce transiently increased blood pressure in patients. The goal of this in vitro study was to examine the effect of indigo carmine on phenylephrine-induced contractions in an isolated rat aorta and to determine the associated cellular mechanism with particular focus on the endothelium-derived vasodilators. METHODS: The concentration-response curves for phenylephrine were generated in the presence or absence of indigo carmine. Phenylephrine concentration-response curves were generated for the endothelium-intact rings pretreated independently with a nitric oxide synthase inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME), a cyclooxygenase inhibitor, indomethacin, and a low-molecular-weight superoxide anion scavenger, tiron, in the presence or absence of indigo carmine. The fluorescence of oxidized dichlorofluorescein was measured in rat aortic vascular smooth muscle cells cultured in the control, indigo carmine alone and tiron plus indigo carmine. RESULTS: Indigo carmine (10(-5) M) increased the phenylephrine-induced maximum contraction in the endothelium-intact rings with or without indomethacin, whereas indigo carmine produced a slight leftward shift in the phenylephrine concentration-response curves in the endothelium-denuded rings and L-NAME-pretreated endothelium-intact rings. In the endothelium-intact rings pretreated with tiron (10(-2) M), indigo carmine did not alter phenylephrine concentration-response curves significantly. Indigo carmine (10(-5) M) increased the fluorescence of oxidized dichlorofluorescein in the vascular smooth muscle cells, whereas tiron abolished the indigo carmine-induced increase in oxidized dichlorofluorescein fluorescence. CONCLUSIONS: Indigo carmine increases the phenylephrine-induced contraction mainly through an endothelium-dependent mechanism involving the inactivation of nitric oxide caused by the increased production of reactive oxygen species.
1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt ; Administration, Intravenous ; Animals ; Aorta ; Blood Pressure ; Contracts ; Fluorescence ; Humans ; Indigo Carmine ; Indoles ; Indomethacin ; Muscle, Smooth, Vascular ; Nitric Oxide ; Nitric Oxide Synthase ; Phenylephrine ; Prostaglandin-Endoperoxide Synthases ; Rats ; Reactive Oxygen Species ; Superoxides

Nanoporous ZnO was used as a carrier to prepare drug solid dispersion, the mechanism of which to improve the drug dissolution was also studied. Nanoporous ZnO, obtained through chemical deposition method, was used as a carrier to prepare indomethacin and cilostazol solid dispersions by melt-quenching method, separately. The results of scanning electron microscope, surface area analyzer, fourier transform infra-red spectroscopy, differential scanning calorimeter and X-ray diffraction showed that drugs were implanted into nanopores of ZnO by physical adsorption effect and highly dispersed into nanopores of ZnO in amorphous form, moreover, these nanopores strongly inhibited amorphous recrystallization in the condition of 45 degrees C and 75% RH. In addition, the results of the dissolution tested in vitro exhibited that the accumulated dissolutions of indomethacin and cilostazol solid dispersions achieved about 90% within 5 min and approximately 80% within 30 min. It was indicated in this study that the mechanism of drug dissolution improvement was associated with the effects of nanoporous ZnO carrier on increasing drug dispersion, controlling drug in nanopores as amorphous form and inhibiting amorphous recrystallization.
Anti-Inflammatory Agents, Non-Steroidal ; administration & dosage ; chemistry ; Calorimetry, Differential Scanning ; Drug Carriers ; Indomethacin ; administration & dosage ; chemistry ; Microscopy, Electron, Scanning ; Nanostructures ; Phosphodiesterase 3 Inhibitors ; administration & dosage ; chemistry ; Solubility ; Spectroscopy, Fourier Transform Infrared ; Tetrazoles ; administration & dosage ; chemistry ; X-Ray Diffraction ; Zinc Oxide ; chemistry