Plant‐derived glucose transport inhibitors with potential antitumor activity

Glucose, a key nutrient utilized by human cells to provide cellular energy and a carbon source for biomass synthesis, is internalized in cells via glucose transporters that regulate glucose homeostasis throughout the human body. Glucose transporters have been used as important targets for the discovery of new drugs to treat cancer, diabetes, and heart disease, owing to their abnormal expression during these disease conditions. Thus far, several glucose transport inhibitors have been used in clinical trials, and increasing numbers of natural products have been characterized as potential anticancer agents targeting glucose transport. The present review focuses on natural product glucose transport inhibitors of plant origin, including alkaloids, flavonoids and other phenolic compounds, and isoprenoids, with their potential antitumor properties also discussed.     

转运体介导的中药和药物间相互作用

中药在我国已应用了数千年,其在疾病治疗、身体保健等方面发挥着非常重要的作用。在临床上,中药往往同其他处方药联合使用。由于中药含有一种或多种药理活性成分,可能诱导或抑制转运体的功能,使药物的药代动力学发生改变,进而影响药物在体内的吸收、分布、代谢和排泄过程,药物的疗效和安全性更是因此受到影响。本文对转运体介导的中药和药物间相互作用作一综述,期望为临床安全合理联合用药提供新思路。     

基于糖基化修饰的靶向药物传递系统研究概况

近年来,基于药物受体及转运体介导的靶向药物传递系统已被广泛研究,靶向药物传递系统增强药物在病变部位的浓度和疗效,最大限度地降低了药物毒副作用。人体不同细胞表面高表达的特异性凝集素受体及脑毛细血管内皮细胞、肿瘤细胞高表达的葡萄糖转运体亚型Ⅰ,可与其相应的糖基配体产生特异性识别。将糖基配体分子如甘露糖、半乳糖、葡萄糖等,键接在药物传递系统上,可赋予其靶向性。这些糖基配体具有无毒、无免疫原性、生物相容性和生物可降解性良好等诸多优点,可广泛用于对药物传递系统的糖基化修饰。本文综述了近5年来糖基化修饰药物传递系统的靶向机制、合成方法及靶向特性,并对其发展前景作了展望。     

Interactions Between Traditional Chinese Medicine and Anticancer Drugs in Chemotherapy

Herbal medicines, including traditional Chinese medicines(TCMs), have been used in Eastern countries for treating diseases such as cancer for thousands of years. With the growing knowledge of tumorigenesis and cancer therapy, some natural compounds have been developed as clinical anticancer drugs. In addition, many compounds and TCMs have been characterized as complementary and alternative treatments,with synergetic effects on enhancing the efficacy or reducing the side effects of the therapeutics. In this review, we summarized the recent studies focusing on the combination of natural compounds or TCM decoction with chemotherapeutics. The detailed mechanisms of action of the combinations and the application of analytical methods on TCM development are also discussed.     

介孔二氧化硅纳米粒在抗肿瘤药物靶向给药系统中的应用

化学疗法是治疗癌症的主要疗法之一,但传统抗肿瘤药在体内呈全身性分布,肿瘤组织内很难达到有效药物浓度,且自身又不具备辨别正常细胞与肿瘤细胞的能力,易造成全身毒性反应,已远远不能满足临床需要。近几年,随着纳米技术的发展及普遍应用,纳米靶向抗肿瘤药物的研究取得了突破性的进展,其中介孔二氧化硅纳米粒(MSNs)在抗肿瘤药物靶向给药系统中的研究日益增多,因其特有的结构及理化特征,具有作用于特定靶点,直接抑制肿瘤细胞的生长,减少对正常细胞和组织器官的毒副作用,可以长期用药等优点,有望成为抗癌药物的优良载体,对MSNs在癌症治疗领域的应用也已成为现在医药领域的研究热点。该文对2008—2015年MSNs在抗肿瘤药物靶向给药系统的最新研究作一综述,分别介绍了MSNs在抗肿瘤药物被动靶向、主动靶向、物理或化学条件响应型靶向及其他复合靶向给药系统中的应用,以期对目前具有良好抗肿瘤作用的化药、天然药物及中药单体化合物的减毒增效及进一步开发提供参考。     

基于乳腺癌耐药蛋白介导的中药-化学药物相互作用研究

中药及其制剂作为临床上重要治疗手段常与化学药物联合使用,因此,应关注中药与化学药物之间的相互作用。乳腺癌耐药蛋白（Breast Cancer Resistance Protein,BCRP）是重要的外排转运体之一,参与体内诸多药物的吸收、分布、代谢、排泄过程。BCRP的表达和外排活性常受相关底物或抑制剂影响,进而改变联合用药的药代动力学,导致药物相互作用。本文主要就银杏、姜黄、甘草、人参、黄芪等常见中药及其主要成分对BCRP的影响及其可能引起的药物相互作用进行综述,为规避临床中药-化学药物联合用药风险提供科学依据。     

致心脏毒性中药的减毒及防治心脏毒性中药的研究进展

心脏毒性是药物临床应用的主要安全性问题之一。近年来,随着对中医药研究的重视与深入,关于对中药心脏安全性的评价与防治心脏毒性反应的研究日益增多,且研究方向集中在致心脏毒性中药的安全使用或靶向心脏的中药毒性成分的发现。关于中药心脏安全性评价的研究方法,该综述介绍了中药心脏安全性评价的临床指标、细胞与动物模型研究进展。关于提升中药心脏安全性的研究,该文回顾总结了常见致心脏毒性中药的毒性物质基础和作用机制,以及通过控制毒性物质含量、改变给药剂型、合理炮制、配伍等方式降低心脏毒性的研究。关于防治心脏毒性的方药与有效成分,该文归纳了近年来防治化疗药物诱导心脏毒性反应的方药及中药有效成分及其作用机制,以期对中药的心脏安全性评价与临床合理应用提供参考。     

Selected Secondary Plant Metabolites for Cancer Therapy

Secondary plant metabolites reveal numerous biological activities making them attractive as resource for drug development of human diseases. As the majority of cancer drugs clinically established during the past half century is derived from nature, cancer researchers worldwide try to identify novel natural products as lead compounds for cancer therapy. Natural products are considered as promising cancer therapeutics, either as single agents or in combination protocols, to enhance the antitumor activity of additional therapeutic modalities. Most natural compounds exert pleotrophic effects and modulate various signal transduction pathways. A better understanding of the complex mechanisms of action of natural products is expected to open new perspectives in coming years for their use alone or in combination therapies in oncology. Two major strategies to identify novel drug candidates from nature are the bioactivity-guided fractionation of medicinal plant extracts to isolate cytotoxic chemicals and the identification of small molecules inhibiting specific targets in cancer cells. In the present review, we report on our own efforts to unravel the molecular modes of action of phytochemicals in cancer cells and focus on resveratrol, betulinic acid, artesunate, dicentrine and camptothecin derivatives.     

P-glycoprotein and its inhibition in tumors by phytochemicals derived from Chinese herbs

P-glycoprotein belongs to the family of ATP-binding cassette (ABC) transporters. It functions in cellular detoxification, pumping a wide range of xenobiotic compounds, including anticancer drugs out of the cell. In cancerous cells, P-glycoprotein confers resistance to a broad spectrum of anticancer agents, a phenomenon termed multidrug resistance. An attractive strategy for overcoming multidrug resistance is to block the transport function of P-glycoprotein and thus increase intracellular concentrations of anticancer drugs to lethal levels. Efforts to identify P-glycoprotein inhibitors have led to numerous candidates, none of which have passed clinical trials with cancer patients due to their high toxicity. The search for naturally inhibitory products from traditional Chinese medicine may be more promising because natural products are frequently less toxic than chemically synthesized substances. In this review, we give an overview of molecular and clinical aspects of P-glycoprotein and multidrug resistance in the context of cancer as well as Chinese herbs and phytochemicals showing inhibitory activity towards P-glycoprotein.     

代谢组学在转运蛋白的生物体内功能分析中的应用

转运蛋白是一种允许有机和无机溶质高效率和选择性跨膜透过的膜蛋白。转运蛋白基因的分子识别即通过克隆cDNA外源表达系统的体外实验方法,阐明转运蛋白的功能。代谢组学分析是通过定量比较某化合物在野生型和转运蛋白基因敲除型小鼠的尿液、血液或组织样本的信息,从而揭示生物体内转运蛋白的真正底物。这种方法也可以用来发现孤儿转运蛋白功能。举例说明基于毛细管电泳与质谱联用（CE—MS）技术,应用代谢组学分析,揭示了SLC22转运蛋白家族中一个孤儿转运蛋白的功能。     

Targeting regulated cell death with plant natural compounds for cancer therapy: A revisited review of apoptosis,autophagy-dependent cell death,and necroptosis

Regulated cell death (RCD) refers to programmed cell death regulated by various protein molecules, such as apoptosis, autophagy-dependent cell death, and necroptosis. Accumulating evidence has recently revealed that RCD subroutines have several links to many types of human cancer; therefore, targeting RCD with pharmacological small-molecule compounds would be a promising therapeutic strategy. Moreover, plant natural compounds, small-molecule compounds synthesized from plant sources, and their derivatives have been widely reported to regulate different RCD subroutines to improve potential cancer therapy. Thus, in this review, we focus on updating the intricate mechanisms of apoptosis, autophagy-dependent cell death, and necroptosis in cancer. Moreover, we further discuss several representative plant natural compounds and their derivatives that regulate the above-mentioned three subroutines of RCD, and their potential as candidate small-molecule drugs for the future cancer treatment.     

纳米技术在改善中药有效成分成药性中的应用

纳米技术在改善中药有效成分成药性方面具有广阔的应用前景和巨大潜力。系统阐述了纳米技术的研究进展,探讨了各种纳米技术的相应制备技术、效果和研究方向。综述纳米技术针对性改善中药有效成分口服吸收、改变体内分布、增加靶向性及改善经皮和黏膜吸收方面的方法与优势;分析了纳米技术在改善中药成药性发展中面临的问题,对解决问题的方案提出设想,并对研究方向进行了展望。     

顺铂毒性损伤机制及中药防治机制的研究进展

顺铂作为临床常用的广谱抗肿瘤药物之一,用于治疗睾丸癌、卵巢癌、头颈癌、膀胱癌、肺癌、宫颈癌等多种实体癌,疗效显著但毒副作用较强,易对机体产生极大的损害,毒性反应可涉及不同脏器造成严重的损伤,诱导机体出现肾损伤、肝损伤、耳损伤、心脏损伤、神经损伤及其他损伤等。动物实验研究发现,顺铂诱导的损伤是由多种因素共同参与的结果,呈时间、剂量依赖性。而在临床使用过程中,顺铂的治疗剂量也因损伤作用受到极大限制,严重影响患者的生存质量。因此,寻找合适的治疗方案或药物与顺铂联合用药实现减毒增效成为目前研究的主要方向。随着中医药在临床参与度的逐渐增加,中医药在治疗疾病方面显示出其特有的优势,可通过改善机体氧化应激状态、抑制正常细胞凋亡及炎症损伤、激活细胞自噬、调节药物转运蛋白的异常表达等途径有效降低顺铂化疗引起的毒性反应,协同顺铂提高化疗疗效。该文通过对顺铂引起机体各脏器的损伤机制及中药防治顺铂损伤的机制2个方面进行详细的概述,其中包括顺铂诱导不同脏器的损伤剂量与机制,中药与顺铂联合应用降低损伤的有效治疗剂量、联合用药方式、防治机制等,以期为中药联合顺铂等化疗药物增效减毒的合理应用及临床用药提供依据。     

中药多糖体内代谢和作用靶点及基于靶点的构效关系研究进展

多糖是由糖苷键结合,在自然界中广泛存在的聚合碳水化合物,作为一类重要的活性天然产物受到越来越多的关注。大量研究证明,中药多糖能够被人体吸收利用,发挥抗肿瘤、免疫调节、抗氧化、降血糖等多种药理活性。近年来,随着复杂中药多糖结构的解析和作用靶点的发现,基于部分作用靶点的中药多糖构效关系被深入阐明。梳理中药多糖在体内吸收、分布、代谢与排泄进展,总结了已发现的中药多糖体内主要作用靶点及基于这些靶点的构效关系的研究新发现,并对基于分子靶点的中药多糖构效关系研究前景进行展望,以期为推动中药药效物质基础研究、促进多糖药物研发提供参考。     

Asperjinone, a nor-neolignan, and terrein, a suppressor of ABCG2-expressing breast cancer cells, from thermophilic Aspergillus terreus

Breast cancer cells express ABCG2 transporters, which mediate multidrug resistance. Discovering a novel compound that can suppress ABCG2 expression and restore drug sensitivity could be the key to improving breast cancer therapeutics. In the current work, one new nor-neolignan, asperjinone (1), as well as 12 other known compounds, was isolated from Aspergillus terreus. The structure of the new isolate was determined by spectroscopic methods. Among these isolates, terrein (2) displayed strong cytotoxicity against breast cancer MCF-7 cells. Treatment with terrein (2) significantly suppressed growth of ABCG2-expressing breast cancer cells. This suppressive effect was achieved by inducing apoptosis via activating the caspase-7 pathway and inhibiting the Akt signaling pathway, which led to a decrease in ABCG2-expressing cells and a reduction in the side-population phenotype.     

中医药治疗去势抵抗性前列腺癌的临床研究进展

中国的前列腺癌发病率不断升高,前列腺癌最终会进展成为去势抵抗性前列腺癌(CRPC).CRPC的治疗有许多问题尚待解决.化疗药物、免疫疫苗及新型内分泌药物等在CRPC的治疗上取得了疗效证据.中医药具有整体调节、扶正祛邪的优势.近年来针对中医药治疗CRPC的病因病机、临床疗效及作用机制开展了卓有成效的研究,中医药为CRPC...     

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??Antitumor drugs have the characteristics of low therapeutic index, narrow safety window, and so on, which are prone to have toxic and side effects in the course of clinical therapy, thus limiting their use. In recent years, some studies have pointed out that the mechanism of adverse reactions of antitumor drugs is related to drug metabolism enzymes, receptors and transporters. Among them, drug metabolism enzymes and their gene polymorphisms play an important role in the toxic and side effects of antitumor drugs. In this paper, we analyze and summarize the side effects of antitumor drugs mediated by drug metabolism enzymes, mainly from the aspects of the roles of metabolic enzymes and their gene polymorphism in the metabolic activation and metabolic detoxification of antitumor drugs, in order to effectively avoid or reduce the toxic side effects of antitumor drugs, and to provide a reference for individualized treatment of cancer.     

代谢酶和转运体介导的中药-环丙沙星潜在相互作用研究进展

中西药联合使用在临床上是常见的。环丙沙星是治疗感染性疾病最常用的氟喹诺酮类药物之一,为提高感染性疾病的治疗效果或应对同时患多种疾病的患者,环丙沙星与一种或多种中药合并使用的现象较为普遍。中药与环丙沙星联用产生的中药-药物相互作用(herb-drug interaction,HDI)可能起到增效减毒的积极作用,也可能导致治疗失败或者发生不良反应。环丙沙星在体内的吸收(absorption,A)、分布(distribution,D)、代谢(metabolism,M)、排泄(excretion,E)等过程,是发生HDI的主要环节。药物代谢酶和转运体对环丙沙星ADME过程的影响近年来备受关注。因此,分别从药物代谢酶、转运体角度对常用中药与环丙沙星之间的直接/潜在相互作用及其作用机制进行综述,以期从药动学方面为环丙沙星与中药的临床合理使用提供依据。     

基于外排转运体的中药解毒作用

中药用于治疗和预防疾病已有数千年的历史.近年来,人们越来越关注中药的毒性作用,特别是通过中药配伍从而降低中药毒性,提高药效的机理.外排转运蛋白是调节药物吸收、代谢、分布、排出的膜转运蛋白,但是中药有效化合物可以通过调控外排转运蛋白从而达到增效减毒作用,这可能是中药配伍的机理之一.因此本综述汇总了中药配伍中常见的有毒药材...