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The anti-oxidant activities of tectochrysin, a major compound of propolis, were investigated. Tectochrysin exhibited a significant decrease in serum transaminase activities elevated by hepatic damage induced by CCl4-intoxication in rats. Tectochrysin tested exhibited a lipid peroxidation causing a significant decrease in MDA production in TBA-reactant assay. Tectochrysin was strong in the increase in the anti-oxidant enzymes such as hepatic cytosolic superoxide dismutase, catalase and glutathione peroxidase activities in CCl4-intoxicated rats. These results suggest that tectochrysin possess not only the anti-oxidant, but also the activities in CCl4-intoxicated rats. Especially, tectochrysin was found to cause significant increases in the rat liver cytosolic SOD, catalase, GSH-px activities as well as a significant decrease in the MDA production. 相似文献
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Summary
Purpose: DDB (dimethyl-4,4′-dimethoxy-5,6,5′6′-dimethylene dioxybiphenyl-2,2′-dicarboxylate) is a synthetic hepatoprotectant which
has been widely used to treat chronic viral hepatitis B patients in China for more than 20 years. In this study, we evaluated
DDB as a multidrug resistance (MDR) chemosensitizing agent.
Methods: A panel of sensitive and resistant cancer cell lines were treated with various concentration of DDB, and the effect on chemosensitivity
and accumulation of anticancer drugs; promotion of apoptosis and P-glycoprotein (P-gp) expression were determined by MTT (Dimethyl
thiazolyl-2,5-diphenyltetrazolium bromide) assay, fluorospectrometry and flow cytometry respectively. Drug resistance reversal
activity of DDB was also examined in BALB/c nude mice bearing both acquired MDR human nasopharyngeal carcinoma KBv200 and
parental KB xenografts. The effect of DDB on the pharmacokinetics of Dox and hematological toxicity induced by Dox was measured
in ICR and C57/BL mice, respectively.
Results: DDB at nontoxic concentrations of 12.5, 25 and 50 μM partly reversed the resistance to vincristine, doxorubicin, paclitaxel
in acquired MDR breast carcinoma MCF-7/Adr cells, KBv200 and intrinsic MDR human hepatocarcinoma Bel7402 cells, whereas no chemosensitizing effect of DDB was observed in sensitive KB and MCF-7 cells. DDB increased the intracellular
accumulation of doxorubicin and inhibited surface P-gp expression in MCF-7/Adr cells. Furthermore, it was found that DDB promoted
doxorubicin-induced apoptosis of Bel7402 cells through enhanced caspase-3 activation. Co-administration of DDB at 300 and 500 mg/kg orally to nude mice increased
the antitumor activity of vincristine to KBv200 xenografts without a significant increase in toxicity. In contrast, Co-administration
of DDB did not inhibit the growth of KB xenografts. DDB also markedly reduced the decrease of leukocytes in doxorubicin-treated
C57/BL mice. Co-administration of DDB increased Dox concentration in ICR mice bearing S180 sarcoma, but no pharmacokinetical
interaction with Dox was observed.
Conclusion: These results indicate that DDB has MDR reversal activity by inhibiting P-gp and when used in combination with anti-cancer
drugs, it could potentially be used as a clinical treatment for P-gp-mediated MDR cancers. 相似文献
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The purpose of the study was to develop a multiunit sustained release dosage form of diltiazem hydrochloride using a natural
polymer, sodium carboxymethyl xanthan gum and polyethyleneimine (PEI) from a completely aqueous environment. PEI treated diltiazem
resin complex loaded beads were characterized by morphology, drug entrapment efficiency, in vitro and in vivo release behaviour. 40% and 80% drug was released in 2 hour in pH 1.2 and in 5 to 6 h in pH 6.8 respectively depending on
the formulation variables. The prolonged release was attributed to decreased swelling of the beads due to PEI treatment. Maintaining
the shape throughout the dissolution process, PEI treated diltiazem resin complex beads released the drug following non-Fickian
transport phenomena. In vivo pharmacokinetic evaluation in rabbits shows slow and prolonged drug release when compared with diltiazem solution. The designed
beads are suitable for prolonged release of a water soluble drug under a complete aqueous environment using natural gum. 相似文献
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In the present study, an extended release pellet dosage form of ketoprofen was prepared using powder layering technique. A
combination of ethyl cellulose (45 cps) and shellac polymers was used as a binder (12% w/w polymer) during drug layering and
an extended release coating (1:3 ratio at 2%, 4% and 7% w/w polymer) within the same apparatus. The coated pellets were characterized
for sphericity, Hardness-Friability Index, and drug content, and also underwent scanning electron microscopy. In vitro dissolution was performed in 900 mL of phosphate buffer (pH 6.8) using paddle apparatus at 100 rpm. Ethyl cellulose and shellac
when used as binders during drug loading did not extend ketoprofen release beyond 3 h. However, coating of the drug loaded
pellets using ethyl cellulose and shellac resulted in an extended release profile of about 10 h. Using Higuchi’s model and
the Korsmeyer equation, the drug release mechanism from the pellets was found to be an anomalous type involving diffusion
and erosion. Scanning electron microscopy was used to visualize the pellet morphology and drug release mechanism during dissolution
testing. In vivo evaluations of the extended release pellets in rats indicated a significant increase in the time to reach maximum concentration
(tmax) and extent of absorption (AUC0-∞) compared to the ketoprofen immediate release tablet blend dispersed and dosed. In conclusion, extended release pellets of
ketoprofen could perform therapeutically better than conventional dosage forms, leading to improved efficacy for a prolonged
period. 相似文献
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Yingqi Hua Zhiyu Zhang Jianxin Li Quan Li Shuo Hu Jian Li Mengxiong Sun Zhengdong Cai 《Investigational new drugs》2011,29(2):258-265
This study was undertaken to investigate the inhibitory effects of triterpenoid compound oleanolic acid and its synthetic
derivatives on osteosarcoma cells in order to identify new therapeutic candidates for the treatment of this disease. We used
the 3-(4,5-dimethyl-2 thiazolyl)-2,5-diphenyl tetrazolium bromide assay to assess the effect of oleanolic acid compounds on
the proliferation of osteosarcoma cells. The effect of dextrose-oleanolic acid (the most potent oleanolic acid derivative)
on apoptosis of osteosarcoma cells was evaluated using the Annexin-V method. The cell cycle of dextrose-oleanolic acid-treated
cells was examined by flow cytometry, and the in vivo effects of dextrose-oleanolic acid were evaluated in a mouse osteosarcoma model. Oleanolic acid compounds had an overall
inhibitory effect on the proliferation of osteosarcoma cells. Our in vitro data showed that the dextrose-oleanolic acid derivative brought about maximal inhibition of proliferation of osteosarcoma
cells while inducing apoptosis. It could also inhibit the growth of osteosarcoma and decreased the rate of lung metastasis
in vivo. Of the oleanolic acid derivatives, dextrose-oleanolic acid exhibited the most potent anti-osteosarcoma activity; it may
represent a new frontier in the treatment of osteosarcoma. 相似文献
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Sun-A. Im Young-Ran Lee Young-Hee Lee Myung-Koo Lee Young In Park Sungwon Lee Kyungjae Kim Chong-Kil Lee 《Archives of pharmacal research》2010,33(3):451-456
The gels of Aloe species contain immunomodulatory components such as aloctin A and acemannan. Most studies on these gels were performed in
in vitro cell culture systems. Although several studies examined their immunomodulatory activity in vivo, the route of administration was intraperitoneal or intramuscular. Here, we evaluated the in vivo immunomodulatory activity of processed Aloe vera gel (PAG) in mice. Oral administration of PAG significantly reduced the growth of C. albicans in the spleen and kidney following intravenous injection of C. albicans in normal mice. PAG administration also reduced the growth of C. albicans in streptozotocin-induced diabetic mice. PAG administration did not increase ovalbumin (OVA)-specific cytotoxic T lymphocyte
(CTL) generation in normal mice, but did increase it in high-fat-diet induced diabetic mice. These findings provide the first
clear evidence for the immunomodulatory activity of orally administered Aloe vera gel. 相似文献
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Purpose
To determine the in vitro sub-cellular localization and in vivo efficacy of chitosan/GMO nanostructures containing paclitaxel (PTX) compared to a conventional PTX treatment (Taxol®).Methods
The sub-cellular localization of coumarin-6 labeled chitosan/GMO nanostructures was determined by confocal microscopy in MDA-MB-231 cells. The antitumor efficacy was evaluated in two separate studies using FOX-Chase (CB17) SCID Female-Mice MDA-MB-231 xenograph model. Treatments consisted of intravenous Taxol® or chitosan/GMO nanostructures with or without PTX, local intra-tumor bolus of Taxol® or chitosan/GMO nanostructures with or without PTX. The tumor diameter and animal weight was monitored at various intervals. Histopathological changes were evaluated in end-point tumors.Results
The tumor diameter increased at a constant rate for all the groups between days 7-14. After a single intratumoral bolus dose of chitosan/GMO containing PTX showed significant reduction in tumor diameter on day 15 when compared to control, placebo and intravenous PTX administration. The tumor diameter reached a maximal decrease (4-fold) by day 18, and the difference was reduced to approximately 2-fold by day 21. Qualitatively similar results were observed in a separate study containing PTX when administered intravenously.Conclusion
Chitosan/GMO nanostructures containing PTX are safe and effective administered locally or intravenously. Partially supported by DOD Award BC04566411.
Bioassay-guided fractionation of the MeOH extract of Suaeda glauca yielded four phenolic compounds, methyl 3,5-di-O-caffeoyl quinate (1) and 3,5-di-O-caffeoyl quinic acid (2), isorhamnetin 3-O-beta-D-galactoside (3), and quercetin 3-O-beta-D-galactoside (4). Compounds 1 and 2 were hepatoprotective against tacrine-induced cytotoxicity in human liver-derived Hep G2 cells with the EC(50) values of 72.7+/-6.2 and 117.2+/-10.5 microM, respectively. Silybin as a positive control showed an EC(50) value of 82.4+/-4.1 microM. 相似文献
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Purpose
Adenoviruses are among the most powerful gene delivery systems. Even if they present low potential for oncogenesis, there is still a need for minimizing widespread delivery to avoid deleterious reactions. In this study, we investigated Magnetofection efficiency to concentrate and guide vectors for an improved targeted delivery. 相似文献13.
Osteoporosis is recognized as a major concern among menopausal women and the elderly. When estrogen is reduced in the body, local factors such as IL-1beta, IL-6 and PGE2, which are known to be related to bone resorption, are increased and promote osteoclastogenesis, which is responsible for bone resorption and results in the clinical disorder osteoporosis. In this study, we investigated the anti-osteoporotic activity of Ficus erecta. MG-63 cells were stimulated with IL-1beta (10 ng/mL) to induce osteoporotic factors (IL-6, COX-2 and PGE2) and RAW 264.7 cells were stimulated with RANKL (100 ng/mL) to induce their differentiation into osteoclasts. We found F. erecta fractions decreased the mRNA expression of IL-6 and COX-2, and protein levels of COX-2 and PGE2 production. Among sequential solvent fractions, hexane and EtOAc fractions decreased differentiation into osteoclasts of RAW 264.7 cells. These results suggest that F. erecta may have significant effects on osteoporotic factors and may be provided as a possible anti-osteoporotic therapeutic plant. 相似文献
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A series of flavonoids (1–14) was isolated from the roots of Sophora flavescens. We evaluated their ability to inhibit both microbial growth and sortase A, an enzyme that plays a key role in cell wall
protein anchoring and virulence in Staphylococcus aureus. Most prenylated flavonoids (7–13) displayed potent inhibitory activity against gram-positive and gram-negative bacteria except E. coli, with minimum inhibitory concentrations values ranging from 4.40 to 27.7 μM, and weak or no activity against fungal strains
tested. Kurarinol (6) was a potent inhibitor of sortase A, with an IC50 value of 107.7 ± 6.6 μM. A preliminary structure-activity relationship, including essential structural requirements, is described. 相似文献
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Chun-Woong Park Yun-Seok Rhee Sung-Hoon Park Son Dao Danh Sung-Hoon Ahn Sang-Cheol Chi Eun-Seok Park 《Archives of pharmacal research》2010,33(3):427-432
Using the nano-composite deposition system (NCDS) as a microfabrication technique, implantable scaffolds were prepared with
poly(DL-lactide-co-glycolide)(85:15) [PLGA(85:15)] as a biodegradable polymer. 5-Fluorouracil (5-FU) was used as a model drug,
and hydroxyapatite (HA) was incorporated as a release modifier. In vitro drug release was evaluated and we confirmed that HA could control the release of drug from the prepared scaffolds, especially
in the initial phase of the release. Furthermore, in vivo tests demonstrated that the microfabricated scaffold with pores was useful in reducing immune response and maintained its
original shape, indicating that the drug delivery system was highly biocompatible. 相似文献
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Kim MJ Han JM Jin YY Baek NI Bang MH Chung HG Choi MS Lee KT Sok DE Jeong TS 《Archives of pharmacal research》2008,31(4):429-437
Oxidized low-density lipoprotein (oxLDL) plays a key role in the inflammatory processes of atherosclerosis. Jaceosidin isolated
from the methanolic extracts of the aerial parts of Artemisia princeps Pampanini cv. Sajabal was tested for antioxidant and anti-inflammatory activities. Jaceosidin inhibited the Cu2+-mediated LDL oxidation with IC50 values of 10.2 μM in the thiobarbituric acid-reactive substances (TBARS) assay as well as the macrophage-mediated LDL oxidation.
The antioxidant activities of jaceosidin were exhibited in the conjugated diene production, relative electrophoretic mobility,
and apoB-100 fragmentation on copper-mediated LDL oxidation. Jaceosidin also inhibited the generation of reactive oxygen species
(ROS) concerning in regulation of NF-κB signaling. And jaceosidin inhibited nuclear factor-kappa B (NF-κB) activity, nitric
oxide (NO) production, and suppressed expression of inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-induced
RAW264.7 macrophages. 相似文献
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The aim of the current work was to design and develop matrix pellets of hydroxy propyl methyl cellulose K200M and microcrystalline
cellulose in an admixture for a mucoadhesive gastroretentive drug delivery system. Pellets containing metformin hydrochloride
(500 mg) were prepared by the pelletization technique using an extruder-spheronizer. Pellets were characterized by differential
scanning calorimetry (DSC), x-ray diffraction (XRD), scanning electron microscopy (SEM), circularity, roundness, percent drug
content, percent production yield, in vitro swelling, ex vivo mucoadhesion, in vitro drug release and in vivo x-ray imaging studies. Optimized pellets were sufficiently porous spheroids, free flowing, had smooth surfaces, had yields
up to 75.45 ± 0.52% and had drug content up to 96.45 ± 0.19%. The average particle size of formulations MF2 and MF6 were 1.13
± 0.41 mm and 1.22 ± 0.18 mm, respectively. Formulation MF6 exhibited strong adhesion, about 94.67%, to goat mucosal tissue,
and the desired in vitro swelling, with a sustained drug release profile for 12 h and with retention in the upper small intestine of rabbits for 10
h. We conclude that hydroxy propyl methyl cellulose K200M and microcrystalline cellulose at a 2.80:1.00 w/w ratio could be
an effective carrier for multiple unit controlled delivery of metformin hydrochloride. 相似文献
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Chunming Lyu Yufeng Zhang Wenbin Zhou Shen Zhang Fang Kou Hai Wei Ning Zhang Zhong Zuo 《The AAPS journal》2016,18(2):432-444
Veratramine, a major alkaloid from Veratrum nigrum L., has distinct anti-tumor and anti-hypertension effects. Our previous study indicated that veratramine had severe toxicity toward male rats. In order to elucidate the underling mechanism, in vivo pharmacokinetic experiments and in vitro mechanistic studies have been conducted. Veratramine was administrated to male and female rats intravenously via the jugular vein at a dose of 50 μg/kg or orally via gavage at 20 mg/kg. As a result, significant pharmacokinetic differences were observed between male and female rats after oral administration with much lower concentrations of veratramine and 7-hydroxyl-veratramine and higher concentrations of veratramine-3-O-sulfate found in the plasma and urine of female rats. The absolute bioavailability of veratramine was 0.9% in female rats and 22.5% in male rats. Further experiments of veratramine on Caco-2 cell monolayer model and in vitro incubation with GI content or rat intestinal subcellular fractions demonstrated that its efficient passive diffusion mediated absorption with minimal intestinal metabolism, suggesting no gender-related difference during its absorption process. When veratramine was incubated with male or female rat liver microsomes/cytosols, significant male-predominant formation of 7-hydroxyl-veratramine and female-predominant formation of veratramine-3-O-sulfate were observed. In conclusion, the significant gender-dependent hepatic metabolism of veratramine could be the major contributor to its gender-dependent pharmacokinetics. 相似文献
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Mamatha Tirunagari Venkateswara Rao Jangala Mukkanti Khagga Ramesh Gannu 《Archives of pharmacal research》2010,33(7):1025-1033
Isradipine (ISDP) is an effective calcium channel blocker used in the treatment of hypertension. It undergoes extensive first
pass metabolism and bioavailability through the oral route is only about 15 to 24%. Hence we attempted to develop a matrix
type controlled transdermal drug delivery system for ISDP. Formulations A1, A2, A3 were composed of Eudragit RL100 and hydroxypropyl
methyl cellulose (HPMC) in 1:3, 1:1, 3:1 ratios; A4, A5, A6 were composed of Eudragit RS100 and HPMC in 1:3, 1:1, 3:1 ratios.
All six formulations carried 5 mg of ISDP/patch area, 5% v/w of D-limonene, 15 % v/w of propylene glycol in methanol:dichloromethane
(1:1). The physicochemical compatibility of the drug and the polymers was studied by infrared spectroscopy and differential
scanning calorimetry. The results suggested no physicochemical incompatibility between the drug and the polymers. The prepared
transdermal drug delivery system were evaluated for physicochemical characteristics, mainly in vitro release and ex vivo permeation. The ex vivo permeation studies were carried out across excised rat skin using Franz diffusion cell. All the formulations exhibited satisfactory
physicochemical characteristics. Cumulative amount of the drug released in 36 h from the six formulations were 1695.32, 1527.89,
1455.54, 1485.65, 1282.81 and 916.88 μg/cm2 respectively. Corresponding values for the cumulative amounts of drug permeated across the rat skin for the above matrix
films were 1456.29, 1284.70, 1182.99, 1212.72, 1046.05, and 782.60 μg/cm2 respectively. By fitting the data into zero order, first order and Higuchi models, it was concluded that drug release from
matrix films followed Higuchi model and the mechanism of drug release was diffusion mediated. Based on the physical evaluation,
in vitro drug release and ex vivo permeation characteristics, it was concluded that for potential therapeutic use, monolithic drug matrix films A1, may be
suitable for the development of a transdermal drug delivery system of ISDP. 相似文献