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941.
Zuo X Djordjevic JT Bijosono Oei J Desmarini D Schibeci SD Jolliffe KA Sorrell TC 《Molecular pharmacology》2011,80(3):476-485
Miltefosine has antifungal properties and potential for development as a therapeutic for invasive fungal infections. However, its mode of action in fungi is poorly understood. We demonstrate that miltefosine is rapidly incorporated into yeast, where it penetrates the mitochondrial inner membrane, disrupting mitochondrial membrane potential and leading to an apoptosis-like cell death. COX9, which encodes subunit VIIa of the cytochrome c oxidase (COX) complex in the electron transport chain of the mitochondrial membrane, was identified as a potential target of miltefosine from a genomic library screen of the model yeast Saccharomyces cerevisiae. When overexpressed in S. cerevisiae, COX9, but not COX7 or COX8, led to a miltefosine-resistant phenotype. The effect of miltefosine on COX activity was assessed in cells expressing different levels of COX9. Miltefosine inhibited COX activity in a dose-dependent manner in Cox9p-positive cells. This inhibition most likely contributed to the miltefosine-induced apoptosis-like cell death. 相似文献
942.
Radix Scutellariae is the dried root of the medicinal plant Scutellariae baicalensis Georgi. It exhibits a variety of therapeutic effects and has a long history of application in traditional formulations as well as in modern herbal medications. It has been confirmed that flavonoids are the most abundant constituents and induce these therapeutic effects. Six flavones are proven to be the major bioactive flavones in Radix Scutellariae existing in the forms of aglycones (baicalein, wogonin, oroxylin A) and glycosides (baicalin, wogonoside, oroxylin A-7-glucuronide). All six flavones are pharmacologically active and show great potential in the treatment of inflammation, cancers and virus-related diseases. The current review covers the preparation of the herb Radix Scutellariae, quantification of its major bioactive ingredients, and pharmacological effects of the proposed six bioactive flavones. In addition, this review summarizes the pharmacokinetic profiles of the bioactive flavones reported so far that could be used for further improvement of their pharmacokinetic study. Moreover, due to abundant co-occurring bioactive components in Radix Scutellariae, our review further documents the pharmacokinetic interactions among them. 相似文献
943.
944.
Baicalein (Ba) was found to be subject to serious first-pass metabolism after oral administration. We previously revealed the important role of intestine in the low oral bioavailability of Ba. The present study aims to evaluate the hepatic metabolism and disposition of Ba. Ba was given to Sprague-Dawley rats through bolus or infusion via intravenous or intra-portal route of administrations. Both plasma and bile samples at different time intervals were obtained. Concentrations of Ba and potential metabolites in the collected samples were analyzed with HPLC/UV and identified by LC/MS/MS, respectively. Plasma concentration versus time profiles of Ba obtained from intravenous and intra-portal administrations were compared to estimate the extent of hepatic metabolism. In addition, transport studies of baicalein-7-glucuronide (BG), one of the major metabolites of Ba, were carried out using transfected cell systems overexpressing various human organic anion-transporting polypeptide (OATP) isoforms to estimate the specific transporters involved in the hepatic disposition of Ba metabolites. The results showed that liver, in addition to intestine, also conferred extensive metabolism to Ba. Several mono- and di-conjugates of Ba, which were mainly glucuronides, sulfates, and methylates, were found in bile. The transport study demonstrated that besides MRPs and BCRP, human OATP2B1 and OATP1B3 in liver might also mediate the secretion of BG to bile. In summary, liver plays an important role in the metabolism of Ba and transport of its conjugated metabolites. 相似文献
945.
946.
目的通过对气相色谱法检测原料乳中农药残留量的测量过程不确定度来源的系统分析,提高对原料乳中农药残留量的检测水平和能力,并找出影响测量结果不确定度的主要因素;方法确立检测过程数学模型,用气相色谱法检测原料乳中有机磷农药残留量、对测量过程不确定度进行评价。结果原料乳中有机磷农药残留量的测量标准不确定度由称量、样品提取过程、稀释过程、标准物质、进样体积和仪器校准值引入的不确定度各组分合成。测量结果的扩展不确定度按式U=k×Cx×urel(合)计算。测定结果报告C=Cx±U,以加入农药标准物质至0.4mg/kg的原料乳做气相色谱法检测6种有机磷残留量分别报告为(0.4±0.050)mg/kg、(0.4±0.029)mg/kg、(0.4±0.027)mg/kg、(0.4±0.029)mg/kg、(0.4±0.057)mg/kg、(0.4±0.034)mg/kg。结论从气相色谱法检测原料乳中农药各组分残留量的测量不确定度分量汇总分析可以看出,测量不确定度一般来源于随机性和模糊性,是由许多分量组成,其分量可用统计分布来进行评价,并且以实验标准(偏)差表征。 相似文献
947.
Chinese medicine has been used to treat a variety of cancer-related conditions. This study aims to examine the prevalence and patterns of Chinese medicine usage by cancer patients. We reviewed articles written in English and found only the Chinese medicine usage from the studies on complementary and alternative medicine (CAM). Seventy four (74) out of 81 articles reported rates of CAM usage ranging from 2.6 to 100%. Acupuncture was reported in 71 out of 81 studies. Other less commonly reported modalities included Qigong (n = 17), Chinese herbal medicine (n = 11), Taichi (n = 10), acupressure (n = 6), moxibustion (n = 2), Chinese dietary therapy (n = 1), Chinese massage (n = 1), cupping (n = 1) and other Chinese medicine modalities (n = 19). This review also found important limitations of the English language articles on CAM usage in cancer patients. Our results show that Chinese medicine, in particular Chinese herbal medicine, is commonly used by cancer patients. Further research is warranted to include studies not written in English. 相似文献
948.
Background
Danshen-Gegen decoction (DG), a Chinese herbal formula, has been demonstrated to be effective for the treatment of coronary heart disease such as myocardial infarction. In the present study, we investigated the effect of DG post-conditioning on isoproterenol (ISO)-induced myocardial injury in rats. 相似文献949.
Epilepsy is the most common serious chronic neurological disorder. Current data show that one-third of patients do not respond to anti-epileptic drugs (AEDs). Most non-responsive epilepsy patients are resistant to several, often all, AEDs, even though the drugs differ from each other in pharmacokinetics, mechanisms of action, and interaction potential. The mechanisms underlying drug resistance of epilepsy patients are still not clear. In recent years, one of the potential mechanisms interesting researchers is over-expression of P-glycoprotein (P-gp, also known as ABCB1 or MDR1) in endothelial cells of the blood-brain barrier (BBB) in epilepsy patients. P-gp plays a central role in drug absorption and distribution in many organisms. The expression of P-gp is greater in drug-resistant than in drug-responsive patients. Some studies also indicate that several AEDs are substrates or inhibitors of P-gp, implying that P-gp may play an important role in drug resistance in refractory epilepsy. In this article, we review the clinical and laboratory evidence that P-gp expression is increased in epileptic brain tissues and that AEDs are substrates of P-gp in vitro and in vivo. We discuss criteria for identifying the substrate status of AEDs and use structure-activity relationship (SAR) models to predict which AEDs act as P-gp substrates. 相似文献
950.
Chen HQ Zuo WJ Wang H Shen HY Luo Y Dai HF Mei WL 《Journal of Asian natural products research》2012,14(5):436-440
Two new flavonoids, named cambodianins D (1) and E (2), together with two known flavanes (2S)-7,4'-dihydroxy-6,8-dimethylflavane (3) and (2S)-7,3'-dihydroxy-4'-methoxy-8-methylflavane (4), were isolated from dragon's blood of Dracaena cambodiana. The new compounds were determined by HR-ESI-MS and spectroscopic techniques (UV, IR, 1D, and 2D NMR). Compounds 1-3 exhibited antimicrobial activities. 相似文献