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Optimizing Growth Conditions for Digoxin Production in Digitalis lanata Ehrh

World Journal of Traditional Chinese Medicine 2016年第2期2卷 24-35页

作者： Herman A.van Wietmarschen Hansj?rg Hagels Ron Peters Jolanda Heistek jan van der greef Mei Wang TNO Netherlands Organization for Applied Scientific Research Microbiology & Systems Biology Sino-Dutch Centre for Preventive and Personalized Medicine Boehringer Ingelheim Pharma Gmb H & Co.KG Business Center Klazienaveen Jolanda: Heistek Result Groenloper SU Bio Medicine

Objective: Digoxin is a therapeutic cardenolide widely used to treat various heart conditions such as atrial flutter, atrial fibrillation and heart failure in both Western as well as Chinese medicine. Digoxin is extracted from cultivated Digitalis lanata Ehrh. plants, known as Mao Hua Yang Di Huang in Chinese medicine. This manuscript presents two studies that were conducted to optimize the cultivation conditions for digoxin production in the TCM Mao Hua Yan Di Huang in a greenhouse under GAP ***: Two experiments were designed in which 4 growth conditions were compared. Levels of digoxin, gitoxin, digitoxin, α-acetyldigoxin, β-acetyl-digoxin were measured using HPLC-UV and compared between the ***: Normal soil, no CO_2 enrichment combined with a cold shock was found to be the optimal condition for producing digoxin in the first experiment. Gitoxin content was significantly lower in plants grown in this condition. Mechanical stress as well as the time of harvesting showed no statistically significant differences in the production of cardenolides. In the second experiment the optimal condition was found to be a combination of cold nights, sun screen, fertilizer use and no milled ***: This study shows that digoxin production can be increased by controlling the growth conditions of D. lanata Ehrh. The effect of cold was important in both experiments for improving digoxin production. Cultivating Chinese herbal medicines in optimized greenhouse conditions might be an economically attractive alternative to regular open air cultivation.

关键词： Digitalis lanata Ehrh mao hua yang di huang cardenolides content optimisation TCM

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Systems Biology:A new analytical based strategy in Life Sciences

Systems Biology:A new analytical based strategy in Life Scie...

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第十五次全国色谱学术报告会

作者： jan van der greef TNO Systems Biology and SU Biomedicine P.O．Box 360 3700 AJ Zeist.The Netherlands Center for Medical Systems Biology／Leiden University 2300 RA Leiden The Netherlands

＜正＞In Life Sciences the improved ability to profile classes of biological elements （genes, proteins, metabolites） has grown tremendously and has created a shift in focus from reductionistic to holistic strategies. This has evolved into a Systems Biology approach, which can be defined as studying biology as an integrated system of genetic, protein, metabolite, cellular and pathway events that are in flux and interdependent.

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Systems biology of resilience and optimal health:integrating Chinese and Western medicine perspectives

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World Journal of Traditional Chinese Medicine 2017年第1期3卷 38-49页

作者： Herman van Wietmarschen Yan Schroёn Victor Kallen Marvin Steijaert Albert A.de Graaf Ben van Ommen jan van der greef TNO The Netherlands Organization for Applied Scientific Research Sino Dutch centre for Preventive and personalized Medicine Louis Bolk Institute Open Analytics

Western science has been strong in measuring details of biological systems such as gene expression levels and metabolite concentrations, and has generally followed a bottom up approach with regard to explaining biological phenomena. Chinese medicine in contrast has evolved as a top down approach in which body and mind is seen as a whole, a phenomenological approach based on the organization and dynamics of symptom patterns. Western and Chinese perspectives are developing towards a ‘middle out' approach. Chinese medicine diagnosis, we will argue, allows bridging the gap between biologists and psychologists and offers new opportunities for the development of health monitoring tools and health promotion *** this paper, health, resilience and stress concepts are explored from an integrated systems biology perspective. This is followed by a discussion about measuring aspects of health and resilience. Then the issue of how to integrate different types of data is discussed. Semi-quantitative modeling appears to be very suitable and looks promising for building integrated health models. The challenge for the future lies in applying those models in developing personalized health monitoring and advice systems that will tempt people to lead more healthy lives.

关键词： Health Wellness Resilience Systems biology Chinese diagnosis

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System Diagnosis:Bridging Chinese and Western Medicine

System Diagnosis:Bridging Chinese and Western Medicine

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第十四届全国中药和天然药物学术研讨会

作者： Mei Wang jan van der greef TNO University of Leiden

＜正＞The shift from a reductionistic towards a systems view is globally a key topic in Life ***-based approaches need the understanding of the interconnectivity of systems and the organizing ***,it requires a shift f...

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Traditional Chinese Medicine-Based Subtyping of Early-Stage Type 2 Diabetes Using Plasma Metabolomics Combined with Ultra-Weak Photon Emission

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Engineering 2019年第5期5卷 916-923页

作者： Min He Mengmeng Sun Slavik Koval Roeland van Wijk Thomas Hankemeier jan van der greef Eduard P.A.van Wijk Mei Wang Leiden University–European Center for Chinese Medicine and Natural Compounds Institute of BiologyLeiden UniversityLeiden 2333 BEthe Netherlands Analytical BioSciences Leiden Academic Center for Drug Research(LACDR)Leiden UniversityLeiden 2333 CCthe Netherlands Changchun University of Chinese Medicine Changchun 130117China Sino-Dutch Center for Preventive and Personalized Medicine Tiel 4002 AGthe Netherlands Meluna Research Geldermalsen 4191 LCthe Netherlands SU Biomedicine Leiden 2300 AMthe Netherlands Shenzhen Huakai Traditional Chinese Medicine and Natural Medicine Research Center Shenzhen 518114China

The prevalence of type 2 diabetes mellitus(T2DM)is increasing rapidly *** of the limited success of generic interventions,the focus of the disease study has shifted toward personalized strategies,particularly in the early stages of the *** Chinese medicine(TCM)is based on a systems view combined with personalized strategies and has improved our knowledge of personalized *** a systems biology perspective,the understanding of personalized diagnostics can be improved to yield a biochemical basis for such strategies;for example,metabolomics can be used in combination with other system-based diagnostic methods such as ultra-weak photon emission(UPE).In this study,we investigated the feasibility of using plasma metabolomics obtained from 44 pre-T2DM subjects to stratify the following TCM-based subtypes:Qi-Yin deficiency,Qi-Yin deficiency with dampness,and Qi-Yin deficiency with *** studied the relationship between plasma metabolomics and UPE with respect to TCM-based subtyping in order to obtain biochemical information for further interpreting disease *** component analysis of plasma metabolites revealed differences among the TCM-based pre-T2DM *** high levels of lipids(e.g.,cholesterol esters and triglycerides)were important discriminators of two of the three subtypes and may be associated with a higher risk of cardiovascular *** metabolomics data indicate that the lipid profile is an essential component captured by UPE with respect to stratifying subtypes of *** results suggest that metabolic differences exist among different TCM-based subtypes of pre-T2DM,and profiling plasma metabolites can be used to discriminate among these *** metabolomics thus provides biochemical insights into system-based UPE measurements.

关键词： Type 2 diabetes mellitus Plasma metabolites Disease subtypes Ultra-weak photon emission Correlation networks

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Improving the analytical strategies for metabolomics

Improving the analytical strategies for metabolomics

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30th International Symposium on Capillary Chromatography、4th GC×GC Symposium、16th National Symposium and Exhibition on Chromatography,i.e. 1st Dalian International Symposium and Exhibition on Chromatography

作者： Thomas Hankemeier Ubbo Tjaden Rob van der Heijden jan van der greef Division Analytical Biosciences LACDR Leiden UniversityEinsteinweg 552333CC LeidenThe Netherlands Division Analytical Biosciences LACDR Leiden UniversityEinsteinweg 552333CC LeidenThe Netherlands Division Analytical Biosciences LACDR Leiden UniversityEinsteinweg 552333CC LeidenThe Netherlands Division Analytical Biosciences LACDR Leiden UniversityEinsteinweg 552333CC LeidenThe Netherlands

＜正＞Metabolic processes are the core of physiology and are therefore indicative of changes in metabolic pathways. As a result,metabolomics is a promising tool to distinguish between health and *** metabolic profiles of patients and healthy controls should play an important role to unravel the biochemical pathways involved in multi-factorial disorders and for early differentiation between health and disease *** fingerprinting of bodyfluids such as blood,urine,and cerebrospinal fluid are expected to become important in predicting disease-risks and treatment *** potential of metabolomics has already been demonstrated, but the sensitivity,specificity,and capacity of the analytical and biostatistical methods have to be further improved.

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Systems biology approach for quality control of Traditional Chinese Medicine(TCM)

Systems biology approach for quality control of Traditional ...

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第十五次全国色谱学术报告会

作者： Wen-Te Chang Thomas Hankemeier jan van der greef TNO Systems Biology and SU Biomedicine P．O.Box 360 3700 AJ Zeist．The Netherlands and Center for Medical Systems Biology／Leiden University 2300 RA Leidenthe Netherlands

Indigenous herbs are very important concept for traditional Chinese medicine (TCM) materials medica production. This means that the highest quality herbs will come from the most suitable areas. For this reason certain areas are known for their specific herbs. A number of factors determine the quality of herbs and have to be taken into consideration in the production of material medica. For instance, the geographical source, including the climate and earth factors which can influence the growth of herbal plants absolutely. In addition, the Processing of TCM materials medica is also a very important part which has a history as long as traditional Chinese herbal medicine itself. It underlines the importance of processing for the clinical effects and the quality of herbs.

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Systems response profiles to two Rehmanniae Radix formulae in metabolic syndrome patients

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World Journal of Traditional Chinese Medicine 2017年第1期3卷 1-10页

作者： Jun-Zeng Fu Herman A.van Wietmarschen jan van der greef Yan Schroёn Mei Wang Division of Analytical Biosciences LACDR Leiden University Sino-Dutch Center for Preventive and Personalized Medicine Louis Bolk Institute SU Bio Medicine Utrechtseweg Oxrider Education and Research

Objective: To explore the effects of two Rehmanniae Radix formulae in patients with metabolic syndrome(Met S), a randomized controlled study was ***: Met S patients were randomly assigned to receive either a classic Rehmanniae Six Formula(R6, or ‘Liu Wei Di Huang Wan') or a novel multi-herbal Rehmanniae Radix containing formula SUB889 for 8 weeks. Western medicine related clinical parameters, Chinese medicine defined symptoms and syndromes as well as metabolomic profiles were evaluated at different time ***: R6(n = 20) and SUB889(n = 20) showed similar effects on Met S regarding the improvement of clinical parameters(waist circumference, body mass index, LDL-cholesterol, systolic blood pressure) and Qi/Yin deficiency(p < 0.05). Decreased levels of cholesteryl esters, phosphatidylcholines, triglycerides and sphingomyelins were found in the R6 group, while SUB889 formula resulted in increased levels of tricarboxylic acid cycle and glucose metabolism intermediates(malate, fumarate and pyruvate).Conclusions: R6 and SUB889 have similar effects on the treatment of Met S by improving Chinese medicine and Western medicine defined clinical outcomes. R6 is more effective in improving lipid profiles compared to SUB889. The exact mechanisms of the two formulae on Met S remain to be elucidated.

关键词： Systems biology Metabolic syndrome Chinese medicine diagnosis Metabolomics Rehmanniae Radix formula

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超高效液相色谱-飞行时间质谱快速分析人参根中的皂甙化合物

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色谱 2011年第6期29卷 488-494页

作者：胡春秀孔宏伟朱超魏恒 Thomas HANKEMEIER jan van der greef 王梅许国旺中国科学院大连化学物理研究所中国科学院分离分析化学重点实验室辽宁大连116023 荷兰莱顿大学分析生物科学部莱顿/阿姆斯特丹药物研究中心荷兰莱顿2333CC 荷兰SU生物医药有限公司及荷兰应用科学研究机构荷兰载斯特3700AJ 华东理工大学药学院上海200237

建立了超高效液相色谱-飞行时间质谱快速分析人参根部提取物中的皂甙类化合物的方法。色谱柱为HSST3超高效液相色谱柱(100 mm×2.1 mm,1.8μm);以15 mmol/L甲酸铵水溶液-乙腈为流动相,采用二元梯度洗脱的方式对人参主根的皂甙提取物进... 详细信息

建立了超高效液相色谱-飞行时间质谱快速分析人参根部提取物中的皂甙类化合物的方法。色谱柱为HSST3超高效液相色谱柱(100 mm×2.1 mm,1.8μm);以15 mmol/L甲酸铵水溶液-乙腈为流动相,采用二元梯度洗脱的方式对人参主根的皂甙提取物进行分离。基于待测目标物的多级质谱碎片离子、精确质量等信息,结合9种人参皂甙标准化合物的多级质谱碎片离子质谱图,共鉴定出人参主根提取物中27种皂甙类化合物。在确定的条件下,以9种人参皂甙标样为研究对象,进行了全面的方法学考察,发现它们的线性范围分别为0.33～9.00 mg/L(Rg1),0.11～9.00 mg/L(Re),0.02～2.00 mg/L(Rf),0.07～6.00 mg/L(Rg2),0.04～3.00 mg/L(Rb1,Rb3),0.22～6.00 mg/L(Rc),0.04～9.00 mg/L(Rb2,Rd);在中等加标浓度时,经内标物峰面积校正的9种皂甙标准化合物的峰面积的相对标准偏差(RSD)不高于11.3%;低、中、高3个质量浓度加标水平的回收率范围分别为90%～100%、98%～104%及96%～103%;最低检出限为3.5～18.5μg/L。该方法具有高分辨、快捷、简便、可靠等特点,并成功地应用于分析同一产地、不同生长时间的人参干燥主根中皂甙的差异。可以预计此方法可进一步应用于各种人参原料和制品中皂甙的快速测定。

关键词：超高效液相色谱质谱人参皂甙人参

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HPLC/LTQ-FTMS用于白参中的丙二酰基人参皂苷的研究

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世界科学技术-中医药现代化 2009年第1期11卷 190-194页

作者：孔宏伟王梅 Rob van der Heijden jan van der greef Thomas Hankemeier 许国旺中国科学院大连化学物理研究所代谢组学研究中心大连116023 荷兰应用科学研究组织(TNO)SU生物药品公司荷兰应用科学研究组织(TNO)生命科学部荷兰莱顿大学荷兰国家代谢组学中心

在15mM甲酸铵作为流动相添加剂条件下,采用HPLC/LTQ-FTMS实现了白参样品中酸性人参皂苷的优化分离。根据高分辨质谱、多级质谱信息,结合保留规律验证,在白参萃取液中共检测和识别了八种丙二酰基人参皂苷,包括丙二酰基人参皂苷Rg1、Re、R... 详细信息

在15mM甲酸铵作为流动相添加剂条件下,采用HPLC/LTQ-FTMS实现了白参样品中酸性人参皂苷的优化分离。根据高分辨质谱、多级质谱信息,结合保留规律验证,在白参萃取液中共检测和识别了八种丙二酰基人参皂苷,包括丙二酰基人参皂苷Rg1、Re、Rf、Rb1、Rc、Rb2、Rb3和Rd。

关键词： HPLC/LTQ—FTMS 丙二酰基人参皂苷白参甲酸铵

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