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??With the continuously clinical study of capsaicin, capsaicin-drug interaction has become increasingly prominent. In recent years, the studies indicate that capsaicin shows a significant inducing or inhibitory effect on a variety of drug metabolism enzymes and transporters, thereby leading to the occurrence of complex drug interactions and affecting the other drugs in vivo process. In this paper, the modulation effect of capsaicin on drug metabolizing enzymes and transporters by reviewing the relevant research at home and abroad in recent years were summarized, and the drug-drug interactions associated with capsaicin in order to provide theoretical guidance for clinical rational drug use were explored . Furthermore, complex drug-drug interaction studies can be provided with prior examples.     

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??Chronic administration of the second-generation antipsychotic drugs (SGAs) is associated with elevated risks of weight gain, obesity and other metabolic disorders, which further leads to an increase in incidence of cardiovascular diseases and the reduced life expectancy in patients. Dyslipidemia is a critical causative factor for the metabolic syndrome. In this article, the potential molecular mechanisms in SGA-induced dyslipidemia were focused on SREBPs/AMPK??/PPAR pathways, as well as the induction of insulin resistance in peripheral tissues (liver and white fat tissue).     

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??OBJECTIVE To investigate the mechanism of hyperthyroid rats treated by thiamazole tablets by the serum metabonomics technology. METHODS Hyperthyroid rats were modeled by subcutaneous injection of L-levothyroxine sodium 35 ??g??100 g^-1 for 7 d. Then rats of thiamazole-treated group were treated by intragastric administration of thiamazole tablets suspension 21 mg??kg^-1 for 21 d. The serum levels of model rats, control rats, thiamazole-treated rats were analyzed by using UPLC-QTOF-MS and UPLC-QTOF-MS was combined with two different modes of positive and negative ions as well as KEGG and HMDB. RESULTS Compared with normal rats, among hyperthyroid rats oxalacetic acid, dihydroxyacetone phosphate (DHAP), ethyl glucuronide, leukotriene E3, hydroxykynurenine, triglycerides (TG) and lysophospholipids were increased. Meanwhile, diacylglycerol (DG) and phosphatidylinositol (PI) were decreased. The 21 d later, the metabolism levels of oxalacetic acid, dihydroxyacetone phosphate, leukotriene E3, phospholipids and fatty acids in thiamazole-treated rats were close to the normality. CONCLUSION The RESULTS infer that tricarboxylic acid cycle of hyperthyroid rat is disturbedall of glucose metabolism, lipid metabolism and amino acid metabolism get into disorder. And these disorders are improved certainly by treating thiamazole. Meanwhile, this method provides an available reference for the establishment of the means of diagnosing hyperthyroidism based on metabonomics and the assessment of the therapeutic effect of thiamazole tablets.     

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??Cardiac hypo-function caused by myocardial ischemia is considered as the first killer of human health. The related metabolites in body can be changed due to the lack of blood and oxygen. These metabolites generated by pathological and physiology changes or exogenous intervention are extreme complicated, and the existing test methods can??t satisfy the prospected purpose due to the lower sensitivity, more narrow liner range and so on. Therefore, the concept of metabonomics, a systemic analysis method, was put forward. Metabolites can be quantified in temporal and spatial dimension by metabonomics featured in a high throughput, higher detective sensitivity and wider liner range manner. So it has gradually been applied to many areas including myocardial ischemia. In this paper, based on the comprehensive research literature in domestic and overseas in recent years, the application of metabonomics in pharmacological research of myocardial ischemia was summarized. Five kinds of metabolic pathways are related with myocardial ischemia including sugar metabolism, energy metabolism, amino acid metabolism, purine metabolism and soluble epoxide hydrolase table oxidase P450 metabolism. Some drugs can be used to myocardial ischemia via these pathways. These representative drugs and their mechanisms which are analyzed by metabonomics were concluded in this paper.     

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??To summarize the research progress of the regulation of lipid metabolism by citrus flavonoids. Recent research articles were analyzed and summarized. Citrus flavonoids are mainly flavanones and polymethoxyflavones, and they can regulate lipid metabolism and prevent atherosclerosis in vitro and in vivo. Factors such as different flavonoid profiles, dosage, time, and experimental models all affect the effectiveness. Citrus flavonoids have great application potentials in regulation of lipid metabolism in vivo, and it has both theoretical and practical significance to screen and study citrus flavonoids.     

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??High-dose methotrexate can obviously reduce tumor recurrence and prolong disease-free survival. But in actual clinical use, the pharmacokinetics and toxicity of the drug show large interpatient variability. Metabolic enzyme and transporter gene polymorphisms may be one of the important influence factors, which are the research focus in recent years. However, different research shows various results. We reviewed the results of related literatures in recent years and the influence of gene polymorphisms of metabolic enzyme and transporter on pharmacokinetic and toxicity of methotrexate were summarized, which can provide information support for the further study of the individualized treatment of methotrexate.     

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??This paper had consulted,analysed,concluded and summarized the studies of nitroimidazoles to expound their basic characteristics, antibacterial activity, metabolic processes and PK/PD characteristics. It could be found by the means of systematic review that nitroimidazoles are widely used in anaerobic and aerobic mixed infections with other drugs, and their metabolic processes in human body areassociated with hepatic cytochrome P450 enzyme system, and AUC/MIC is the optimal parameters for evaluating PK/PD characteristics of metronidazole. But the specific mechanisms and PK/PD characteristicsof nitroimidazoles need further exploration and research.     

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??Urotensin ?? (U??) and urotensin ?? receptor (UTR) have significant effects on the pathogenesis of type 2 diabetes (T2D). UTR, as a G protein-coupled receptor (GPCR), mediates U?? signal transduction.The gene polymorphism of U?? and UTR is high related to the susceptibility of diabetes, suggesting a relationship between U?? system and T2D. U?? system can influence the process of T2D by affecting body weight, lipid and glucose metabolism and inflammatory response. U?? can also induce insulin resistance by regulating insulin-related signaling pathway or accelerating oxidative stress.Therefore, U?? system might be a potential target for T2D treatment.     

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??The rapid development of modern analytical technology provides many methods of detecting drugs and their metabolites. LC-MS/MS technology has become one of the most commonly used methods in drug metabolites analysis with its characteristics of simpleness and high efficiency. In this paper, based on the published articles of in vivo drug metabolites study by LC-MS/MS in recent years, the processes of data acquisition and processing, metabolites detecting and identification and software-assisting were summarized. This article provides references for research on drug metabolism using LC-MS/MS.     

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??RNA interference technology(RNAi) has a great potential in the biomedical field, providing a very good idea for the research and development of new drugs because of its high efficiency, high specificity, and low toxicity. Rational design strategies, chemical modifications and nanocarriers offer significant opportunities to overcome the deficiencies of siRNA drugs such as rapid degradation, poor cell uptake and off-target effects. Here, the research progress of some siRNA drugs which have entered clinical trials was reviewed based on their indications, administration routes and nanocarriers, which provides references for researchers in development of siRNA drugs.     

大毒中药对机体的不良反应和肝脏药物代谢酶调节研究进展

近十几年来,随着中药在世界的应用范围不断扩大,中华人民共和国药典中所记载的10种大毒中药也逐渐被应用于临床。但人体服用此类药物后,在肝脏药物代谢酶的介导下达到治疗效果的同时,也可能会对代谢酶产生影响,从而造成机体器官的损伤等不良反应,严重时会危及到人的生命。因此,对大毒中药的不良反应和肝脏代谢酶研究极为重要。本文将10种大毒中药国内外的相关研究资料进行总结,为大毒中药的研究和临床的合理应用提供科学依据。     

几种抗肿瘤药物研究进展

目的：开展马钱子、雄黄和半夏的化学成分、抗肿瘤机制及不良反应的进展研究,为临床上进一步研究减毒增效、提高安全性和疗效提供参考。方法：综述近年来对马钱子、雄黄及半夏的化学成分、抗肿瘤作用及不良反应的最新研究进展。结果：研究表明在肿瘤治疗中的应用越来越广泛,既有确切的疗效,又具有较大的不良反应。结论：对马钱子、雄黄及半夏的不良反应,进行＂量-效＂和＂量-毒＂关系研究,观察其在人体内的代谢情况,提高其临床安全性和疗效仍将是今后重要的研究方向。     

氧化石墨烯作为抗肿瘤药物纳米载体的性能研究进展

氧化石墨烯由于其特殊的理化性质现已在各种领域得到了广泛的应用。在肿瘤治疗方面,其常被用作抗肿瘤药物的载体。鉴于其表面丰富的修饰位点,可有目的性地对其表面结构进行改造与修饰以更好地发挥其载药与释药作用。本文综述了部分国内外对其结构改造方面的研究以及将其作为抗肿瘤药物载体的研究,旨在为今后进一步开发其在抗肿瘤方面的应用提供理论依据。     

当归总多糖对小鼠肝脏药物代谢酶活性具有调节作用

目的:观察当归总多糖(ASP)对正常及泼尼松龙(PSL)所致肝损伤小鼠肝脏药物代谢酶活性的影响。方法:PSL皮下注射15mg·kg^-1,连续5d造成小鼠肝损伤。酶学测定Ⅱ相酶谷胱甘肽相关酶活性;测定细胞色素P450(CYP)含量、NADPH-细胞色素C还原酶、氨基比林N-脱甲基酶(AMD)及苯胺羟化酶(ANH)活性。结果:ASPig使正常小鼠肝微粒体及线粒体谷胱甘肽S-转移酶(GST)活性升高,肝线粒体谷胱甘肽(GSH)含量、谷胱甘肽还原酶活性无明显改变,对肝微粒体细胞色素P450酶系统有诱导作用。大剂量PSL使小鼠血清ALT明显升高,肝线粒体GSH含量明显下降,上述各项酶活性升高。ASP对PSL所致酶活性及GSH含量改变有恢复作用。结论:ASP具有调节肝脏药物代谢酶活性作用。     

神曲与酶对化风丹药母发酵过程中毒性成分的影响

目的:探讨神曲与酶对化风丹药母发酵过程中双酯型生物碱类成分含量的影响。方法:设置α-淀粉酶组、胃蛋白酶组、胰蛋白酶组、脂肪酶组、混合酶组、原处方组和阴性组,采用HPLC测定发酵4周后7组化风丹药母中乌头碱、新乌头碱、次乌头碱的含量,流动相乙腈-四氢呋喃(25∶15,A)-0.1 mol·L-1乙酸铵溶液(每1 L加冰乙酸0.5 m L,B)梯度洗脱(0~22 min,20%~23%A;22~40 min,23%~25%A),检测波长235 nm。结果:发酵4周后,7组药母样品中双酯型生物碱类成分含量均明显降低,各组均未检测到乌头碱,3种双酯型生物碱总和降低率66.67%~81.72%,其中α-淀粉酶组降低率最高;多重比较显示各组间3种双酯型生物碱类成分含量总和存在明显差异,α-淀粉酶组样品中3种双酯型生物碱类成分含量总和显著低于原处方组,胃蛋白酶组和阴性组均显著高于原处方组,胰蛋白酶组、脂肪酶组、混合酶组与原处方组无显著性差异,阴性组样品中3种双酯型生物碱类成分含量显著高于其他6组。结论:神曲与酶对化风丹药母发酵过程中双酯型生物碱类成分的降解具有一定促进作用,α-淀粉酶促进效果较为显著。     

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??OBJECTIVE To identify the specific cytochrome P450 (CYP) enzymes involved in the metabolism of dipfluzine hydrochloride (Dip) in the rat liver microsomes. METHODS The rat liver microsomes were prepared and incubated with Dip. The Dip metabolites (M1, M2, M4 and M5) were identified by LC-MS/MS, and the CYP isoenzymes were identified by the combination of the selective CYP inhibitor study, correlation analysis and a panel of recombinant rat CYP expereiment, respectively. RESULTS The RESULTS from the experiments of selective CYP inhibitors, correlation analysis and recombinant rat CYP isoenzymes indicated that CYP2A1, CYP3A and CYP2C11 contributed to the formation of M1 and M5 in the rat liver microsomes. CYP3A, CYP2A1, CYP1A2, CYP2C11 and CYP2E1 metabolized Dip to M2. CYP3A, CYP2A1, CYP2E1 and CYP2C11 contributed to M4 formation. And the recombinant rat CYP researches further indicated that CYP3A2 exhibited more activity than CYP3A1. CONCLUSION CYP3A and CYP2A1 are the major CYP isoenzymes responsible for catalyzing Dip to the four metabolites formation in the rat liver microsomes.     

铂类抗肿瘤药物靶向给药的研究进展

 目的阐述铂类抗肿瘤药物靶向给药的研究进展。方法分析、归纳、总结最近发表的文献。结果与结论靶向给药是降低铂类药物的毒性和克服其耐药性最有效的方法之一,受到广泛研究,取得了重要的进展。铂类药物的靶向给药研究主要集中在:①铂类药物靶向制剂;②含大分子聚合物载体的铂配合物;③含肿瘤中高表达受体的配基的铂配合物;④铂类药物前药。     

猕猴桃根的抗肿瘤作用及临床研究进展

肿瘤目前是世界范围最常见的疾病之一,其发病率和致死率均逐年递增,已成为危害人类健康的头号杀手。中医学认为肿瘤多是本虚标实之证,恶性肿瘤发病的关键病理基础为火热之毒,因此,清热解毒法乃是治疗肿瘤的重要治疗法则之一,应贯穿治疗本病之始终。猕猴桃根是具有代表性清热解毒中药,具有抗肿瘤等生物活性,在抗肿瘤作用的临床研究中取得了显著疗效。近几年临床对猕猴桃根的研究较多,在广泛文献检索基础上,总结猕猴桃根有效部位筛选、有效成分以及不同肿瘤类型临床研究,对猕猴桃根抗肿瘤作用和临床应用以及药理活性成分进行综述,以证实猕猴桃根具有良好的抗肿瘤作用,开发以及应用前景优秀。     

抗肿瘤药物引起手足综合征机制及中西医结合治疗进展

手足综合征是许多抗肿瘤药的常见副反应之一,现代医学多从病理机制方面对其进行研究,而中医学则从病因病机方面进行辨证,两种医学均取得显著的成效。中西医结合的治疗措施可缓解症状,提高患者的生存质量。在未来对手足综合征的研究中,还需更深层次的探索。     

中药抗肿瘤机制研究浅析

许多中药具有抗肿瘤作用 ,因中药成分复杂 ,其抗肿瘤机理也表现在多个方面。本文对抗肿瘤中药的特点、作用机制进行了简单归纳、总结。