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101.
Mohammad Raish Ajaz Ahmad Mushtaq Ahmad Ansari Khalid M. Alkharfy Abdul Ahad Altaf Khan Fahad I. Aljenobi Naushad Ali Abdullah M. Al-Mohizea 《Yao wu shi pin fen xi = Journal of food and drug analysis.》2019,27(1):332
Dietary supplements and foods can interact with various drugs, leading to possible clinical concerns. This study aimed to investigate the effect of orally administered sinapic acid (SA) on the pharmacokinetics of aripiprazole (APZ) in rats and its possible modulatory effects on hepatic cytochrome P450 (CYP3A2 and CYP2D6) expression in the liver tissues. Single dose and multiple dose parallel groups of wistar rats were categorized into six groups (n = 6 each) which abstained from food for 12 h prior to the experiment, while water was allowed ad libitum. The investigation was carried out for single dose: Group I was treated with normal saline orally for 15 days (normal control). Group II was administered normal saline orally for 15 days and received APZ (3 mg/kg p.o.) on day 15. Group III received SA (20 mg/kg p.o.) for 15 days and received APZ (3 mg/kg p.o.) on day 15. Group IV was treated with SA (20 mg/kg p.o.) for 15 days. For the multiple dose study, Group I was treated with normal saline orally for 15 days (normal control); Group II received APZ (3 mg/kg p.o.) daily for 15 days; Group III was administered with SA (20 mg/kg p.o.) and APZ (3 mg/kg p.o.) for 15 days and Group IV received SA (20 mg/kg p.o.) for 15 days. The group I and IV were kept common in single and multiple dose groups. After last APZ dose, plasma samples were collected and APZ concentrations were determined using an UPLC-MS/MS technique. The pharmacokinetic parameters were calculated using a non-compartmental analysis. The concomitant administration of APZ with SA (as single or multiple dose) resulted in an increase in APZ absorption and a decrease on its systemic clearance. This was associated with a reduction in CYP3A2 and CYP2D6 protein expressions by 33–43% and -71–68% after the single and multiple co-administration, which are two enzymes responsible of the metabolism of APZ. Therefore, a reduction in the metabolic clearance appears to be the mechanism underlying the drug interaction of dietary supplement containing SA with APZ. Therefore, the concomitant administration of SA and APZ should be carefully viewed. Further investigations are required to assess the clinical significance of such observations in humans. 相似文献
102.
Martin Werle Brigitta Loretz Daniel Entstrasser Florian Föger 《Journal of drug targeting》2013,21(5):327-333
One main barrier for the peroral administration of therapeutic peptides and proteins is the enzymatic barrier, that is mediated by luminally secreted and membrane bound proteolytic enzymes. It was the aim of the study to synthesise, characterise and evaluate a novel polymer–inhibitor conjugate in order to improve the bioavailability of orally-administered peptides and proteins. The trypsin/chymotrypsin inhibitor aprotinin was covalently bound to chitosan. The percentage of the inhibitor in the polymer–inhibitor conjugate (m/m) was determined to be between 1.11 ± 0.36 and 1.92 ± 0.05%. In vitro enzyme assays clearly demonstrated the potential of the novel conjugate to inhibit trypsin and chymotrypsin. Moreover, studies in rats were performed to evaluate the efficacy of the conjugate in vivo. Eight hours after oral administration of tablets containing insulin and the novel chitosan–aprotinin conjugate, the mean blood glucose level decreased to 84 ± 6%. In contrast, the mean blood glucose level in the control group increased to 121 ± 8% of the initial measured blood glucose level. In conclusion it was demonstrated that chitosan–aprotinin conjugate represents a novel and promising tool for the oral administration of therapeutic peptides and proteins susceptible to enzymatic degradation caused by trypsin and chymotrypsin. 相似文献
103.
104.
Evidence that genetic deletion of the TNF receptor p60 or p80 inhibits Fas mediated apoptosis in macrophages 总被引:3,自引:0,他引:3
Almost 19 members of the tumor necrosis factor (TNF) superfamily have been identified that interact with 29 different receptors. Whether these receptors communicate with each other is not understood. Recently, we have shown that receptor activator of NF-kappaB ligand signaling is modulated by genetic deletion of the TNF receptor. In the current report, we investigated the possibility of a cross-talk between Fas and TNF-alpha signaling pathway in macrophage cell lines derived from wild-type (WT) mice and from mice with genetic deletion of the type 1 TNF receptor (p60(-/-)), the type 2 TNF receptor (p80(-/-)), or both receptors (p60(-/-)p80(-/-)). We found that the macrophages expressing TNF receptors were highly sensitive to apoptosis induced by anti-Fas. The genetic deletion of TNF receptors, however, made the cells resistance to anti-Fas-induced apoptosis. Anti-Fas induced activation of caspase-3 and PARP cleavage in WT cells but not in TNF receptor-deleted cells. This difference was found to be independent of the expression of Fas, Fas-associated protein with death domain (FADD) or TNF receptor-associated death domain (TRADD). We found that anti-Fas induced recruitment of TNFR1 into Fas-complex. We also found that TRADD, which mediates TNF signaling, was constitutively bound to Fas receptor in TNF receptor-deleted cells but not in wild-type cells. Transient transfection of TNFR1 in TNFR1-deleted cells sensitized them to anti-Fas-induced apoptosis. Overall our results demonstrate that Fas signaling is modulated by the TNF receptors and thus provide the evidence of cross-talk between the receptors of two cytokines. 相似文献
105.
Xinming Li John Tsibouklis Tingting Weng Buning Zhang Guoqiang Yin Guangzhu Feng 《Journal of drug targeting》2017,25(1):17-28
Effective therapy lies in achieving a therapeutic amount of drug to the proper site in the body and then maintaining the desired drug concentration for a sufficient time interval to be clinically effective for treatment. The blood–brain barrier (BBB) hinders most drugs from entering the central nervous system (CNS) from the blood stream, leading to the difficulty of delivering drugs to the brain via the circulatory system for the treatment, diagnosis and prevention of brain diseases. Several brain drug delivery approaches have been developed, such as intracerebral and intracerebroventricular administration, intranasal delivery and blood-to-brain delivery, as a result of transient BBB disruption induced by biological, chemical or physical stimuli such as zonula occludens toxin, mannitol, magnetic heating and ultrasound, but these approaches showed disadvantages of being dangerous, high cost and unsuitability for most brain diseases and drugs. The strategy of vector-mediated blood-to-brain delivery, which involves improving BBB permeability of the drug–carrier conjugate, can minimize side effects, such as being submicrometre objects that behave as a whole unit in terms of their transport and properties, nanomaterials, are promising carrier vehicles for direct drug transport across the intact BBB as a result of their potential to enter the brain capillary endothelial cells by means of normal endocytosis and transcytosis due to their small size, as well as their possibility of being functionalized with multiple copies of the drug molecule of interest. This review provids a concise discussion of nano carriers for drug transport across the intact BBB, various forms of nanomaterials including inorganic/solid lipid/polymeric nanoparticles, nanoemulsions, quantum dots, nanogels, liposomes, micelles, dendrimers, polymersomes and exosomes are critically evaluated, their mechanisms for drug transport across the BBB are reviewed, and the future directions of this area are fully discussed. 相似文献
106.
目的观察薯蓣皂苷片对类风湿性关节炎模型大鼠血清骨保护素(OPG)、核因子-κB受体活化因子配体(RANKL)表达水平的影响。方法 SD大鼠,随机分为6组,每组10只,其中选取10只作为正常组,其余大鼠采用弗氏完全佐剂复制类风湿性关节炎动物模型,并将造模成功的类风湿性关节炎大鼠随机分为模型组、阳性组(甲氨蝶呤组,3.8mg·kg~(-1))、薯蓣皂苷片高、中、低剂量组(10 mg·mL~(-1)、20 mg·mL~(-1)、30mg·mL~(-1)),连续灌胃给药治疗24 d后处死,采用ELISA法检测血清OPG、RANKL水平。结果薯蓣皂苷片各剂量组大鼠血清OPG、RANKL水平分别为(95.27±4.24)、(76.44±4.09)、(69.26±5.63)pmol·L~(-1)和(96.07±4.94)、(85.41±3.75)、(67.53±2.23)pmol·L~(-1),与模型组((53.92±2.83)pmol·L~(-1)和(116.18±3.02)pmol·L~(-1))相比均有显著性差异(P0.05);OPG/RANKL比值显著高于模型组。结论薯蓣皂苷片可能通过调整OPG/RANKL动态平衡而对破骨细胞功能产生影响,从而防止骨破坏。 相似文献
107.
核因子-κB(RANK)和其配体RANKL的,属于肿瘤坏死因子受体激活剂(TNF)受体配体的家庭的一员,二者结合后,破骨细胞活性增强,引起的骨吸收。而骨保护素(OPG)能与RANK竞争RANKL,抑制破骨细胞的过度表达,或者能干扰骨髓基质细胞与破骨细胞之间相互作用而诱导破骨细胞的凋亡,RANK/RANKL/OPG系统参与了不同疾病的骨吸收导致一系列溶骨性病变。骨代谢疾病中RANKL和OPG的问题,为治疗方案提供了新的靶标,正成为临床相关研究的热点之一。 相似文献
108.
Preeti Kumari Omkara Swami Muddineti Sri Vishnu Kiran Rompicharla Pratyusha Ghanta Adithya Karthik B B N Balaram Ghosh 《Drug delivery》2017,24(1):209-223
Polymeric micelles have been widely explored preclinically as suitable delivery systems for poorly soluble chemotherapeutic drugs in cancer therapy. The present study reported the development of cholesterol (Ch)-conjugated poly(D,L-Lactide) (PLA)-based polymeric micelles (mPEG–PLA-Ch) for effective encapsulation and delivery of curcumin (CUR) at the tumor site. Cholesterol conjugation dramatically affected the particle size and improved drug loading (DL) and encapsulation efficiency (EE). mPEG–PLA-Ch-CUR showed bigger hydrodynamic diameter (104.6?±?2.1?nm, and 169.3?±?1.52?nm for mPEG–PLA and mPEG–PLA-Ch, respectively) due to increased size of the hydrophobic core. The newly developed polymer exhibited low critical micelles concentration (CMC) (25?μg/mL) which is close to lipid-based polymer, PEG-phosphatidyl ethanolamine (12.5?μg/mL) compared to mPEG–PLA (50?μg/mL). mPEG–PLA-Ch micelles exhibited relatively higher EE (93.74?±?1.6%) and DL (11.86?±?0.8%) compared to mPEG–PLA micelles (EE 91.89?±?1.2% and DL 11.06?±?0.8%). mPEG–PLA-Ch micelles were internalized by the cancer cells effectively and exhibited higher cytotoxicity compared to free CUR in both, murine melanoma (B16F10) and human breast cancer (MDA-MB-231) cells. mPEG–PLA-Ch exhibited satisfactory hemocompatibility indicating their potential for systemic application. Further, mPEG–PLA-Ch-CUR demonstrated higher rate of reduction of tumor volume in B16F10-xenografted tumor-bearing mice compared to free CUR. At the end of 22 days, the tumor reduced to 1.87-fold (627.72?±?0.9?mm3 versus 1174.68?±?1.64?mm3) compared to the treatment with free CUR. In conclusion, the experimental data in vitro and in vivo indicated that the newly developed CUR-mPEG–PLA-Ch micelles may have promising applications in solid tumors. 相似文献
109.
The mulberry tree (Morus alba) plays a key role in agriculture, and its different parts have been used as popular Traditional Chinese Medicines for thousands of years. There are 16 species belonging to the Morus genus. Among them, 11 species distribute in China, most of which have been used as the substitutes of M. alba in local provinces. This review summarizes the structural characters of polyphenols, the main components in Morus, including Diels–Alder-type adducts, flavonoids, 2-arylbenzofurans, and stilbenes, and also their related bioactivities in the last 10 years. 相似文献
110.
目的探讨Grb2-相关蛋白2(Gab2)在核因子-κB受体活化因子配体(RANKL)诱导的乳腺癌细胞MDA-MB-213迁移中的作用。方法流式细胞术检测MDA-MB-231细胞表面RANK的表达。Transwell法测定RANKL刺激后细胞迁移能力的改变。免疫沉降及Western-blot检测RANKL刺激后p-Tyr-Gab2和Gab2的表达。结果 MDA-MB-231细胞表达RANK蛋白,RANKL诱导MDA-MB-231细胞迁移能力增强。RANKL刺激后MDA-MB-231细胞p-Tyr-Gab2表达一过性升高。结论 Gab2参与RANKL诱导的乳腺癌细胞MDA-MB-231迁移。 相似文献