- Email: [email protected]
Systems approach for evaluation the biological effects of multi-herbal Chinese medicine formula
698
Abstracts / European Journal of Integrative Medicine 6 (2014) 686–745
receptor mediating way. In addition, wnt/-catenin, NF-B and EGFR signaling also play important roles in the process. These findings provide novel insight into the mechanism underlying glycans against cancer and pave the way to support the development of new oral glycan-based drugs. Acknowledgements: This work was supported by grants of the New Drug Creation and Manufacturing Program (2012ZX09301001-003), the National Science Fund for Distinguished Young Scholars in China (81125025) and the National Natural Science Foundation of China (NSFC) (31230022).
purine and pyrimidine and eight mercaptan amino acid, as well as the fourteen diabetic nephropathy related gene. The established IBS can be used for the auxiliary diagnosis of diabetic nephropathy with Qi and Yin deficiency as well as the efficacy evaluation of Tangshen formula. The preferred research would provide relevant reference material for the application of systems biology on TCM clinic research and practice. Thirdly, a “focus mode” of integrated biomarker system was established, which was applied in the description of TCM doseeffect relationship, and it’s also could be applied to elucidate the correlation between animal model and clinical research.
http://dx.doi.org/10.1016/j.eujim.2014.09.030 http://dx.doi.org/10.1016/j.eujim.2014.09.031 Integrative biomarker system for clinical systems biology of TCM Guoan Luo ∗ , Yiming Wang Department of Chemistry, Tsinghua University, China E-mail address: [email protected] (G. Luo). The establishment of appropriate strategy and methodology adapted to the fundamental characteristics of traditional Chinese medicine (TCM) is a key issue, and it is imperative to verify the value of TCM in modern medicine. The most important problem in TCM research should be how to represent the holistic efficacy of Chinese medicine. Whether the holistic efficacy of TCM can be described via various data obtained in systems biology research at different biological levels (for example, genomics, metabonomics or/and proteomics)? and, How to construct a methodology which is suitable for both animal model and clinical research? Under the guidance of holism and systematic theory, clinical systems biology was proposed in order to accommodate the needs of TCM clinical research and translational medicine, which aims at promoting the modernization and internationalization of TCM with the “system-to-system” research mode. The proposed clinical systems biology mainly covers these three aspects. Firstly, the clinical systems biology research system should be constructed which characterized by multi-level biomarker group. And the application of this research system will set up a bridge between TCM and western medicine. Secondly, the integrated biomarker system should be composed of multi-level indicators, including TCM syndrome indicators, clinic biomedical indicators, imaging indexes as well as systems biology biomarker groups. The established integrated biomarker system can be applied to early warning of disease, clinical diagnosis and treatment, personalized medicine, disease prognosis as well as the efficacy evaluation. The recently TCM clinical systems biology research on diabetic nephropathy of our group was used as an example in this paper to introduce the proposed idea. The tentative integrated biomarker system (IBS) has been discovered and screened on the basis of TCM syndrome indicators, clinic biomedical indicators, together with some systems biology biomarkers, which obtained by metabolic profiling analysis, quantitative analysis of fifteen fatty acids, twenty-one
Systems approach for evaluation the biological effects of multi-herbal Chinese medicine formula Mei Wang 1,2,∗ , Herman A. van Wietmarschen 1 , Yan Schroën 1 , Jan van der Greef 1,2 1 Sino-Dutch
Centre for Preventive and Personalized Medicine, Zeist, The Netherlands 2 SU BioMedicine, Utrechtseweg, Zeist, The Netherlands E-mail address: [email protected] (M. Wang). Chinese and Western medicines have different approaches for the treatment of disease that is mainly due to different cultural background and as a result has led to two different ways of conducting science and medicine. Western medicine is currently facing the challenge of rapidly rising costs and decreasing new effective drugs. The future lies in personalized medicine which can be developed by the integration of Chinese and Western medicines. A systems biology approach is used to capture Chinese and Western types of patient information. Pre-diabetes is taken as examples to show how a systems biology approach together with Chinese symptom profiles has resulted in finding relevant sub-types of patients and understanding the biology of these sub-types. For intervention strategy, a multi-herbal formula was used for treatment of diabetes related disease. Rehmannia Six Formula (R6 or Liu Wei Di Huang Wan) is an important classic Chinese medicine formula used to treat metabolic disorders related to aging. It was first reported in the Chinese medicine book titled ‘Xiao Er Yao Zheng ZhiJue by Qian Yi’ (Chinese Song dynasty: 1035-1117). Changes in symptoms, clinical parameters and serum metabolite profiles during R6 treatment of human subjects with features of metabolic syndrome were measured. The symptoms ‘hectic fever’ and ‘spontaneous sweating’ were found to be most relieved during R6 treatment. LDL-c, total cholesterol, systolic blood pressure and waist size were found to decrease during R6 treatment. Additionally, ten of the fifteen measured phosphatidylcholines were found to decrease. Personalized symptom profiles show that large Yin deficiencies are addressed first by R6 treatment. However, in subjects with low Yin deficiency but which do have a substantial Qi deficiency a reduction of Qi deficiency is observed. The observed decrease of Yin deficiency
Abstracts / European Journal of Integrative Medicine 6 (2014) 686–745
related symptoms is in agreement with the use of R6 in Chinese medicine to nourish Yin. The effect of R6 was found to be different for the Yin deficiency subjects and the Qi deficiency subjects. Measuring personalized treatment effects is therefore an essential step in the development of personalized medicine. http://dx.doi.org/10.1016/j.eujim.2014.09.032 Supercritical fluid chromatography in natural product analysis Sonja Sturm, Judith Taibon, Hermann Stuppner ∗ Institute of Pharmacy/Pharmacognosy, University of Innsbruck, Center of Molecular Biosciences Innsbruck (CMBI), Innrain 80/82, 6020 Innsbruck, Austria E-mail address: [email protected] (H. Stuppner). When supercritical fluid chromatography was first developed more than 50 years ago, it was considered as a revolutionary separation technique. However, it never emerged from the shade of GC and HPLC and its reputation slowly ebbed over the years. Within the last decade, the revived interest of manufacturers and scientists for this complementary technique which combines some of the best features of LC as well as GC lead to tremendous improvement of the SFC instrumentation resulting in a stable analytical platform with many advantages over the existing chromatographic methods. SFC has been approved as versatile, cost-efficient, green, user friendly high resolution technique with multi-detector compatibility. It can be applied for the separation of complex mixtures instead of normal phase LC minimizing the use of toxic solvents or reversed phase LC without the need to convert samples to highly aqueous diluents, or in the case of hydrophobic thermo-labile or non-volatile compounds instead of GC without any derivatization. Whereas in the past SFC has mainly been used for the analytical or preparative separation of chiral compounds, it is getting more and more attention in the arena of achiral separation nowadays. Several recent reviews reported various applications in the field of drug discovery or food analysis with emphasis on exceeding lipophilic substance classes as lipids or fatty acids. However, reports on the successful separation of more polar natural compounds are rare up to now. In our laboratories we recently evaluated the applicability of SFC for qualitative and quantitative analysis of various classes of compounds with interesting biological activities; amongst them plant and fungus derived constituents, as cyclic peptides, triterpenoids, diterpenoids, alkaloids and many more. SFC might be the longed for technique to fill the gap between LC and GC allowing high-throughput, high-resolution but also cost-effective and environmental-friendly analysis for a tremendous expanded field of possible applications in natural product analysis. http://dx.doi.org/10.1016/j.eujim.2014.09.033
699
Novel analytical tools for quality control in Traditional Chinese Medicine Christian W. Huck Institute of Analytical Chemistry and Radiochemistry, CCB – Center for Chemistry and Biomedicine, Leopold-Franzens University, Innrain 80/82, 6020 Innsbruck, Austria E-mail address: [email protected]. Due to the amount of immunomodulatory, anti-inflammatory and neuroprotective agents in Traditional Chinese Medicine (TCM) novel analytical tools are permanently demanded to ensure at any time quality and safeness. Therefore, it is our aim to further develop vibrational spectroscopic methodologies allowing estimating the quality of a medicinal plant during breeding by near-infrared spectroscopy (NIRS), infrared (IR) imaging on one hand and mass spectroscopic imaging techniques on the other hand. The immunomodulatory, anti-inflammatory and neuroprotective potential of deriving extracts are optimised employing Aquasolv® -procedures next to conventional extraction methods. IR based metabolic profiling is carried out employing multivariate data analysis to monitor any changes in quality. For a more detailed, selective and sensitive insight miniaturised liquid chromatographic methods hyphenated to mass spectrometry (-LC–MS) via an electrospray (ESI) or matrix-free material enhanced laser desorption ionisation (mf-MELDI) interface are applied using designed and tailored stationary phases. These analytical tools are helpful to monitor the immunomodulatory, anti-inflammatory and neuroprotective effects and are also applicable in bioguided isolation approaches and cell based screening assays. As some potent ingredients might be available in only very low amounts special pre-concentration techniques, e.g. hollow monoliths, are introduced. In this presentation the establishment of a systematic analytical platform for the screening of wrong constituents while increasing the quality and safety is reported. http://dx.doi.org/10.1016/j.eujim.2014.09.034 Challenges and solutions for the quality control of natural health products Yuan-Chun Ma Canadian Phytopharmaceuticals Corp., Vancouver, BC, Canada E-mail address: [email protected]. Standardization and efficient quality control are the most important issues in the natural health products industry today and require world-wide attention, action, and resolution. After analyzing a number of commercial products including some of the most popular options currently in the market, it is evident that major quality control problems plague the industry. Such issues include: the incorrect labelling of plant species, the lack of detectable active compounds present, lowered concentrations, and extracts spiked with related compounds in a bid to meet the
Abstracts / European Journal of Integrative Medicine 6 (2014) 686–745
receptor mediating way. In addition, wnt/-catenin, NF-B and EGFR signaling also play important roles in the process. These findings provide novel insight into the mechanism underlying glycans against cancer and pave the way to support the development of new oral glycan-based drugs. Acknowledgements: This work was supported by grants of the New Drug Creation and Manufacturing Program (2012ZX09301001-003), the National Science Fund for Distinguished Young Scholars in China (81125025) and the National Natural Science Foundation of China (NSFC) (31230022).
purine and pyrimidine and eight mercaptan amino acid, as well as the fourteen diabetic nephropathy related gene. The established IBS can be used for the auxiliary diagnosis of diabetic nephropathy with Qi and Yin deficiency as well as the efficacy evaluation of Tangshen formula. The preferred research would provide relevant reference material for the application of systems biology on TCM clinic research and practice. Thirdly, a “focus mode” of integrated biomarker system was established, which was applied in the description of TCM doseeffect relationship, and it’s also could be applied to elucidate the correlation between animal model and clinical research.
http://dx.doi.org/10.1016/j.eujim.2014.09.030 http://dx.doi.org/10.1016/j.eujim.2014.09.031 Integrative biomarker system for clinical systems biology of TCM Guoan Luo ∗ , Yiming Wang Department of Chemistry, Tsinghua University, China E-mail address: [email protected] (G. Luo). The establishment of appropriate strategy and methodology adapted to the fundamental characteristics of traditional Chinese medicine (TCM) is a key issue, and it is imperative to verify the value of TCM in modern medicine. The most important problem in TCM research should be how to represent the holistic efficacy of Chinese medicine. Whether the holistic efficacy of TCM can be described via various data obtained in systems biology research at different biological levels (for example, genomics, metabonomics or/and proteomics)? and, How to construct a methodology which is suitable for both animal model and clinical research? Under the guidance of holism and systematic theory, clinical systems biology was proposed in order to accommodate the needs of TCM clinical research and translational medicine, which aims at promoting the modernization and internationalization of TCM with the “system-to-system” research mode. The proposed clinical systems biology mainly covers these three aspects. Firstly, the clinical systems biology research system should be constructed which characterized by multi-level biomarker group. And the application of this research system will set up a bridge between TCM and western medicine. Secondly, the integrated biomarker system should be composed of multi-level indicators, including TCM syndrome indicators, clinic biomedical indicators, imaging indexes as well as systems biology biomarker groups. The established integrated biomarker system can be applied to early warning of disease, clinical diagnosis and treatment, personalized medicine, disease prognosis as well as the efficacy evaluation. The recently TCM clinical systems biology research on diabetic nephropathy of our group was used as an example in this paper to introduce the proposed idea. The tentative integrated biomarker system (IBS) has been discovered and screened on the basis of TCM syndrome indicators, clinic biomedical indicators, together with some systems biology biomarkers, which obtained by metabolic profiling analysis, quantitative analysis of fifteen fatty acids, twenty-one
Systems approach for evaluation the biological effects of multi-herbal Chinese medicine formula Mei Wang 1,2,∗ , Herman A. van Wietmarschen 1 , Yan Schroën 1 , Jan van der Greef 1,2 1 Sino-Dutch
Centre for Preventive and Personalized Medicine, Zeist, The Netherlands 2 SU BioMedicine, Utrechtseweg, Zeist, The Netherlands E-mail address: [email protected] (M. Wang). Chinese and Western medicines have different approaches for the treatment of disease that is mainly due to different cultural background and as a result has led to two different ways of conducting science and medicine. Western medicine is currently facing the challenge of rapidly rising costs and decreasing new effective drugs. The future lies in personalized medicine which can be developed by the integration of Chinese and Western medicines. A systems biology approach is used to capture Chinese and Western types of patient information. Pre-diabetes is taken as examples to show how a systems biology approach together with Chinese symptom profiles has resulted in finding relevant sub-types of patients and understanding the biology of these sub-types. For intervention strategy, a multi-herbal formula was used for treatment of diabetes related disease. Rehmannia Six Formula (R6 or Liu Wei Di Huang Wan) is an important classic Chinese medicine formula used to treat metabolic disorders related to aging. It was first reported in the Chinese medicine book titled ‘Xiao Er Yao Zheng ZhiJue by Qian Yi’ (Chinese Song dynasty: 1035-1117). Changes in symptoms, clinical parameters and serum metabolite profiles during R6 treatment of human subjects with features of metabolic syndrome were measured. The symptoms ‘hectic fever’ and ‘spontaneous sweating’ were found to be most relieved during R6 treatment. LDL-c, total cholesterol, systolic blood pressure and waist size were found to decrease during R6 treatment. Additionally, ten of the fifteen measured phosphatidylcholines were found to decrease. Personalized symptom profiles show that large Yin deficiencies are addressed first by R6 treatment. However, in subjects with low Yin deficiency but which do have a substantial Qi deficiency a reduction of Qi deficiency is observed. The observed decrease of Yin deficiency
Abstracts / European Journal of Integrative Medicine 6 (2014) 686–745
related symptoms is in agreement with the use of R6 in Chinese medicine to nourish Yin. The effect of R6 was found to be different for the Yin deficiency subjects and the Qi deficiency subjects. Measuring personalized treatment effects is therefore an essential step in the development of personalized medicine. http://dx.doi.org/10.1016/j.eujim.2014.09.032 Supercritical fluid chromatography in natural product analysis Sonja Sturm, Judith Taibon, Hermann Stuppner ∗ Institute of Pharmacy/Pharmacognosy, University of Innsbruck, Center of Molecular Biosciences Innsbruck (CMBI), Innrain 80/82, 6020 Innsbruck, Austria E-mail address: [email protected] (H. Stuppner). When supercritical fluid chromatography was first developed more than 50 years ago, it was considered as a revolutionary separation technique. However, it never emerged from the shade of GC and HPLC and its reputation slowly ebbed over the years. Within the last decade, the revived interest of manufacturers and scientists for this complementary technique which combines some of the best features of LC as well as GC lead to tremendous improvement of the SFC instrumentation resulting in a stable analytical platform with many advantages over the existing chromatographic methods. SFC has been approved as versatile, cost-efficient, green, user friendly high resolution technique with multi-detector compatibility. It can be applied for the separation of complex mixtures instead of normal phase LC minimizing the use of toxic solvents or reversed phase LC without the need to convert samples to highly aqueous diluents, or in the case of hydrophobic thermo-labile or non-volatile compounds instead of GC without any derivatization. Whereas in the past SFC has mainly been used for the analytical or preparative separation of chiral compounds, it is getting more and more attention in the arena of achiral separation nowadays. Several recent reviews reported various applications in the field of drug discovery or food analysis with emphasis on exceeding lipophilic substance classes as lipids or fatty acids. However, reports on the successful separation of more polar natural compounds are rare up to now. In our laboratories we recently evaluated the applicability of SFC for qualitative and quantitative analysis of various classes of compounds with interesting biological activities; amongst them plant and fungus derived constituents, as cyclic peptides, triterpenoids, diterpenoids, alkaloids and many more. SFC might be the longed for technique to fill the gap between LC and GC allowing high-throughput, high-resolution but also cost-effective and environmental-friendly analysis for a tremendous expanded field of possible applications in natural product analysis. http://dx.doi.org/10.1016/j.eujim.2014.09.033
699
Novel analytical tools for quality control in Traditional Chinese Medicine Christian W. Huck Institute of Analytical Chemistry and Radiochemistry, CCB – Center for Chemistry and Biomedicine, Leopold-Franzens University, Innrain 80/82, 6020 Innsbruck, Austria E-mail address: [email protected]. Due to the amount of immunomodulatory, anti-inflammatory and neuroprotective agents in Traditional Chinese Medicine (TCM) novel analytical tools are permanently demanded to ensure at any time quality and safeness. Therefore, it is our aim to further develop vibrational spectroscopic methodologies allowing estimating the quality of a medicinal plant during breeding by near-infrared spectroscopy (NIRS), infrared (IR) imaging on one hand and mass spectroscopic imaging techniques on the other hand. The immunomodulatory, anti-inflammatory and neuroprotective potential of deriving extracts are optimised employing Aquasolv® -procedures next to conventional extraction methods. IR based metabolic profiling is carried out employing multivariate data analysis to monitor any changes in quality. For a more detailed, selective and sensitive insight miniaturised liquid chromatographic methods hyphenated to mass spectrometry (-LC–MS) via an electrospray (ESI) or matrix-free material enhanced laser desorption ionisation (mf-MELDI) interface are applied using designed and tailored stationary phases. These analytical tools are helpful to monitor the immunomodulatory, anti-inflammatory and neuroprotective effects and are also applicable in bioguided isolation approaches and cell based screening assays. As some potent ingredients might be available in only very low amounts special pre-concentration techniques, e.g. hollow monoliths, are introduced. In this presentation the establishment of a systematic analytical platform for the screening of wrong constituents while increasing the quality and safety is reported. http://dx.doi.org/10.1016/j.eujim.2014.09.034 Challenges and solutions for the quality control of natural health products Yuan-Chun Ma Canadian Phytopharmaceuticals Corp., Vancouver, BC, Canada E-mail address: [email protected]. Standardization and efficient quality control are the most important issues in the natural health products industry today and require world-wide attention, action, and resolution. After analyzing a number of commercial products including some of the most popular options currently in the market, it is evident that major quality control problems plague the industry. Such issues include: the incorrect labelling of plant species, the lack of detectable active compounds present, lowered concentrations, and extracts spiked with related compounds in a bid to meet the