Fangjiomics: In Search of Effective and Safe Combination Therapies

Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China.
The Journal of Clinical Pharmacology (Impact Factor: 2.48). 08/2011; 51(8):1132-51. DOI: 10.1177/0091270010382913
Source: PubMed


Millennia-old Chinese medicine treats disease with many combination therapies involving ingredients used in clinic practice. Fangjiomics is the science of identifying and designing effective mixtures of bioactive agents and elucidating their modes of action beyond those of Chinese patent medicines. Omics profiling and quantitative optimal modeling have been used to associate the various responses with biological pathways related to disease phenotype. Fangjiomics seeks to study myriad compatible combinations that may act through multiple targets, modes of action, and biological pathways balancing on off-target and on-target effects. This approach may lead to the discovery of controllable array-designed therapies to combine less potent elements that are more effective collectively but have fewer adverse side effects than does any element singly.

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    • "Because TCM has a holistic approach, system biology and –omics technologies are probably the most appropriate ways to understand the mechanisms that underlie the therapeutic effects of these mixtures (Qiu, 2007; Tian, 2011). Recent projects go in this direction, such as " Fangjiomics " that aims to identify and design effective mixtures of bioactive agents and elucidating their modes of action (Wang et al., 2011), while " Chinmedomics " refers to the metabolomics of TCM formulae (Wang et al., 2012a). Large noncommercial TCM databases have been constructed to support those efforts (Chen, 2011; Xue et al., 2013). "
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    ABSTRACT: Nuclear receptors (NRs) are major pharmacological targets that allow an access to the mechanisms controlling gene regulation. As such, some NRs were identified as biological targets of active compounds contained in herbal remedies found in traditional medicines. We aim here to review this expanding literature by focusing on the informative articles regarding the mechanisms of action of traditional Chinese medicines (TCMs). We exemplified well-characterized TCM action mediated by NR such as steroid receptors (ER, GR, AR), metabolic receptors (PPAR, LXR, FXR, PXR, CAR) and RXR. We also provided, when possible, examples from other traditional medicines. From these, we draw a parallel between TCMs and phytoestrogens or endocrine disrupting chemicals also acting via NR. We define common principle of action and highlight the potential and limits of those compounds. TCMs, by finely tuning physiological reactions in positive and negative manners, could act, in a subtle but efficient way, on NR sensors and their transcriptional network.
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    • "For instance, PhytomicsQC, a platform for quality control of botanical drugs, provides an information-rich approach to determining the batch-to-batch similarity of botanical extracts [19]. HM formulae , however, are absorbed in spectra-based effects indicating that different pharmacological activities are resulted from the variation of ingredients profile due to the fact that same compound would have different pharmacological activities and analogs would have overlapping medical functions [23]. Moreover, climatic conditions , geographic locations, methods of harvest, processing and extraction can have an impact on the composition of the final product [1]. "
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    ABSTRACT: Although herbal medicine (HM) behaves as a complex system having high-potential for treating chronic/life-threatening diseases, compatible characterization metrics with hierarchical approaches to integrate molecular-level information into the whole system are lacking. Herein, we report a high-throughput methodology (holographic infrared (IR) spectroscopy) harmonizing with the character of HM, providing hierarchical infrared fingerprints (entirety, parts and single ingredients), and working as a "GPS" to navigate a comprehensive chemical characterization of HM circularly from system to molecular level by step-by-step HM analysis-through-separation of IR spectra indicative and vice versa by reconstitution-through-combination of adducting spectrum without a complete understanding of the chemical constituents, and demonstrate holographic chemical charaterization of a Chinese herb Danshen. Global chemical fingerprints of species at each hierarchical level and ingredient profile variations among multilevel species of Danshen are integratively interpreted with fast estimation of their relative contents of active compounds. Finally, integral dynamic information of Danshen separation process is disclosed straightforward by spectral retrieving technique.
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    ABSTRACT: To identify natural and original kinase inhibitors from plant extracts, we have developed and compared a heterogeneous enzyme-linked immunosorbent assay (ELISA) and a homogeneous time-resolved fluorescence (HTRF, Cisbio International, Bagnols/Cèze, France) assay. Kinase affinity for the ATP substrate was determined in both assays, and the same [ATP]/ATP Km ratio was used in each case to enable the identification of ATP competitive and noncompetitive inhibitors. Assays were then used to screen the same collection of chemical compounds and plant extracts. The intra-assay correlation analysis of each technology showed a very good screening precision in HTRF and an acceptable one in ELISA. When the two methods were compared, a poor correlation was obtained with a higher hit rate in the ELISA. We then performed a detailed study of the ELISA hits and showed that they also presented a strong antioxidant activity, associated with high adsorption into microplate wells, which interfered with the horseradish peroxidase-based detection system. These hits were then flagged as false-positives. We also showed that many plant extracts presented this kind of activity and that this interference could explain the lack of correlation between the assays. These findings suggest that assay design should be carefully adapted to the substances to be screened and that interferences should be extensively considered before any assay development process and comparison studies. In spite of a few interferences, our results showed that a homogeneous-phase assay like the HTRF assay could be more efficiently used for plant extract screening than a heterogeneous-phase assay like ELISA.
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