Xenobiotic-metabolizing enzymes in plants and their role in uptake and biotransformation of veterinary drugs in the environment

Many various xenobiotics permanently enter plants and represent potential danger for their organism. For that reason, plants have evolved extremely sophisticated detoxification systems including a battery of xenobiotic-metabolizing enzymes. Some of them are similar to those in humans and animals, but there are several plant-specific ones. This review briefly introduces xenobiotic-metabolizing enzymes in plants and summarizes present information about their action toward veterinary drugs. Veterinary drugs are used worldwide to treat diseases and protect animal health. However, veterinary drugs are also unwantedly introduced into environment mostly via animal excrements, they persist in the environment for a long time and may impact on the non-target organisms. Plants are able to uptake, transform the veterinary drugs to non- or less-toxic compounds and store them in the vacuoles and cell walls. This ability may protect not only plant themselves but also other organisms, predominantly invertebrates and wild herbivores. The aim of this review is to emphasize the importance of plants in detoxification of veterinary drugs in the environment. The results of studies, which dealt with transport and biotransformation of veterinary drugs in plants, are summarized and evaluated. In conclusion, the risks and consequences of veterinary drugs in the environment and the possibilities of phytoremediation technologies are considered and future perspectives are outlined.     

Applications of mass spectrometry in drug metabolism: 50 years of progress

Abstract

Mass spectrometry plays a pivotal role in drug metabolism studies, which are an integral part of drug discovery and development nowadays. Metabolite identification has become critical to understanding the metabolic fate of drug candidates and to aid lead optimization with improved metabolic stability, toxicology and efficacy profiles. Ever since the introduction of atmospheric ionization techniques in the early 1990s, liquid chromatography coupled with mass spectrometry (LC/MS) has secured a central role as the predominant analytical platform for metabolite identification as LC and MS technologies continually advanced. In this review, we discuss the evolution of both MS technology and its applications over the past 50 years to meet the increasing demand of drug metabolism studies. These advances include ionization sources, mass analyzers, a wide range of MS acquisition strategies and data mining tools that have substantially accelerated the metabolite identification process and changed the overall drug metabolism landscape. Exemplary applications for characterization and identification of both small-molecule xenobiotics and biological macromolecules are described. In addition, this review discusses novel MS technologies and applications, including xenobiotic metabolomics that hold additional promise for advancing drug metabolism research, and offers thoughts on remaining challenges in studying the metabolism and disposition of drugs and other xenobiotics.     

Metabolism of Chinese Materia Medica in Gut Microbiota and Its Biological Effects

The drug metabolism in gut microbiota draws increasing attentions. After interacting with the gut bacteria, the biological effects of drugs might be altered, leading to toxicity or detoxification, production of potential bioactivities, regulating intestinal absorption, etc. In this review, we will focus on the metabolism of Chinese materia medica(CMM) in mammal gut microbiota and its biological effects to learn the interaction between gut bacteria and drugs through oral route in CMM.     

影响白术挥发油积累因素的研究进展

菊科苍术属白术Atractylodes macrocephala的干燥根茎为白术的药用部位,是常用的传统中药,具有健脾、美容等功效。挥发油是白术的主要药用成分,其中主要含有倍半萜类化合物,具有明显的抗肿瘤作用。近年来,白术的市场需求量逐渐增加,然而其质量却参差不齐。对白术次级代谢产物挥发油中倍半萜的生物合成和转化途径进行综述,并从遗传和生态角度总结了影响白术挥发油积累的主要因素,以期为研究白术倍半萜的合成和转化途径提供参考,为提高白术挥发油的产量和品质提供帮助。     

红曲霉发酵转化人参皂苷Rg_3的研究

目的探索红曲霉对人参的固态发酵工艺,将人参中部分主要人参皂苷转化为生物活性更强的稀有人参皂苷Rg_3(Rg_3)。方法采用静止暗培养方法进行微生物发酵;香草醛-冰醋酸法测定发酵前后人参总皂苷含量;HPLC法测定发酵前后Rg_3含量。结果红曲霉发酵人参的最优工艺参数为发酵时间6 d、发酵温度32℃、发酵pH 7.0、基质含水量50%。发酵6 d时,发酵产物人参总皂苷质量分数增加40%,Rg_3质量分数为6.047 mg/g,是未发酵人参的2.3倍。最终根据单体皂苷含量随发酵时间的变化趋势,推断稀有皂苷Rg_3的转化路径为人参皂苷Rb_1或Rb_2→Rd→Rg_3。结论建立的红曲霉固态发酵工艺合理,为稀有皂苷Rg_3定向化生产奠定了基础,更为日后体外制备稀有人参皂苷提供了理论支持。     

Inhibition of Staphylococcus Aureus Mediated by Extracts from Iranian Plants

In order to find new antibacterial agents effective against Staphylococcus aureus, ethanolic extracts of 10 plants were tested. S. aureus (489 samples) were isolated either from healthy carriers (nose and throat) or clinical samples. Out of 489 isolates tested, 98.6% were sensitive to trimethoprim-sulfamethoxazole which was used as the reference antibiotic. From the plant extracts screened for antibacterial activity, Myrtus communis L. (leaves) had the greatest activity, inhibiting the growth of 99% of the isolates. Glycyrrhiza glabra L., Eucalyptus globolus Labill and Menta viridis L., were also active against the isolates inhibiting the growth of 90, 59.5 and 48.7% of the isolates, respectively. All of these extracts were active against the reference strains of S. aureus tested. Saturia hortensis L., Teucrium polium L., and Achillea santolina L., had very little antibacterial activity, while Trigonella foenum graecum L., Echium amoenum Fisch & Mey (flowers) and Juglans regia L. (leaves), had no antibacterial activity against the bacterial isolates.     

红球菌g26中C17位脱氢酶的克隆表达及生物转化

目的对红球菌g26中的短链脱氢酶基因进行克隆表达并考察其能否将甾体化合物雄甾-4-烯-3.17-二酮(androst-4-ene-3,17-dione,AD) C17位羰基还原为羟基。方法通过检索数据库获得红球菌g26中的两个短链脱氢酶基因,应用PCR、重组表达载体的构建等生物技术在大肠杆菌中进行外源表达,破碎细胞后应用SDS-PAGE对可溶性蛋白进行分析,筛选出合适的目的蛋白诱导条件,进而进行酶的体外转化反应,应用薄层色谱分析、高效液相分析和质谱法鉴定产物结构。结果与结论红球菌g26中的短链脱氢酶可以转化甾体化合物AD为睾丸酮(TS)。红球菌g26内的短链脱氢酶参与了甾体化合物C17位羰基到羟基的还原反应。     

Biotransformation of melatonin in human breast cancer cell lines: role of sulfotransferase 1A1

The biologically active melatonin metabolite, 6-hydroxymelatonin (6-OHMel), is conjugated to form 6-hydroxymelatonin sulfate (6-OHMelS). To elucidate the role of the sulfotransferase (SULT) enzyme 1A1, considerably expressed in normal and malignant human breast cells, we measured the formation of 6-OHMelS by ELISA in hormone-dependent MCF-7 and hormone-independent MDA-MB231 (MDA) breast cancer cell lines after stable transfection with SULT1A1. In parent MDA cells, low SULT1A1 mRNA expression was associated with moderate 6-OHMelS formation as determined after application (24 hr) of 0.1 microM 6-OHMel. As expected, overexpression of SULT1A1 in MDA cells resulted in a 2.9- and 110-fold increase in 6-OHMelS in the cytosol and cellular supernatant respectively. Furthermore, 6.3- and 115-fold increases were observed after 0.5 microM, and 12.6- and 101-fold increases after 1 microM 6-OHMel respectively. In MCF-7 cells, because of high basal SULT1A1 expression, only two- to threefold increases in 6-OHMelS were observed after transfection with the enzyme. In total, 866 and 539 pmol/mg protein 6-OHMelS were formed from 1 microM 6-OHMel in SULT1A1 overexpressing MDA and MCF-7 cells, respectively, whereas application of 1 microM melatonin produced only <1% of 6-OHMelS. Possible interactions with the SULT1A1 substrate tamoxifen (tam), an anti-estrogen applied in the therapy of breast cancer, were also studied. A concentration of 1 microM tam increased 6-OHMelS formation by approximately threefold in the presence of 1 microM melatonin or 1 microM 6-OHMel respectively. However, no alterations were detected after application of 1 microM 4-hydroxy-tamoxifen. In summary, we demonstrate the importance of SULT1A1 for the biotransformation of 6-OHMel in human breast cancer cells. Our data further suggest that tam can modulate melatonin biotransformation.     

杜仲内生真菌的分离鉴定及其对异甜菊醇的生物转化研究

目的:从植物杜仲的根、茎、叶中分离内生真菌并进行初步鉴定,并研究获得的杜仲内生真菌对异甜菊醇的生物转化活性。方法:采用形态学方法对分离菌株进行鉴定,并对其进行异甜菊醇生物转化活性筛选实验。结果:从健康杜仲的根、茎、叶中分离获得52株内生真菌,属于2纲,2目,4科,10属。其中有4株内生真菌对异甜菊醇具有生物转化活性,分别为交链孢霉Alternaria sp.EL3、瘤座霉Tubercularia sp.ER3、镰孢霉Fusarium sp.EL7及青霉Penicillium sp.ES2。结论:杜仲内生真菌多样性丰富,部分内生真菌对异甜菊醇具有生物转化活性,具有很好的研究和应用价值。     

小克银汉霉属微生物模型在体外药物代谢研究中的应用

药物代谢在药效和安全性评价中是非常重要的,而利用微生物转化为药物体外代谢模型则具有很多优势。小克银汉霉属的许多菌株具有与人体类似的Ⅰ相和Ⅱ相药物代谢酶,其微生物模型能对多种底物进行高效转化。本文对其在药物代谢方面的应用进行综述,并对其未来的发展进行了展望。