Chinmedomics: A Powerful Approach Integrating Metabolomics with Serum Pharmacochemistry to Evaluate the Efficacy of Traditional Chinese Medicine

Evaluation of the efficacy of traditional Chinese medicines (TCMs) is an important prerequisite for discovering effective substances, lead compounds, and quality markers (Q markers). At present, there is an urgent need to develop a biological language that can act as abridge for the scientific elaboration of the efficacy of TCMs, and to further highlight the significant value of TCM. Chinese medicinal syndromes and formulae are two essential parts of TCM that directly relate to its efficacy. Syndromes and formulae have been taken as the research objects. The serum pharmacochemistry of the TCM approach with metabolomics were integrated to establish an innovative chinmedomics strategy, which is able to explore syndrome biomarkers and evaluate TCM efficacy in order to discover effective substances from TCMs. A great deal of concrete work in chinmedomics has already performed to bridge the gap between Chinese and Western medicine, and to provide a powerful approach to enhance the scientific value of TCM theory and clinical practice. This article summarizes the application of chinmedomics in identifying the candidate biomarkers of a syndrome and revealing the efficacy of the related formula. We also highlight the discovery of lead compounds and Q markers from TCMs.

Overview on metabolomics in traditional Chinese medicine

Metabolomics has been widely used in the modern research of traditional Chinese medicine （TCM）. At the same time, the world is increasingly concerned about TCM, and many studies have been conducted to investigate different aspects of TCM. Among these studies, metabolomic approach has been implemented to facilitate TCM development. The current methods for TCM research are diverse, including nuclear magnetic resonance, gas chromatography-mass spectrometry, and liquid chromatographymass spectrometry. Using these techniques, some advantageous results have been obtained in the studies of TCM, such as diagnosis and treatment, quality control, and mechanisms of action. It is believed that the further development of metabo-lomic analytical techniques is benefcial to the modernization of TCM. This review summarizes potential applications of metabolomics in the area of TCM. Guidelines for good practice for the application of metabolomics in TCM research are also proposed, and the special role of metabolomics in TCM is highlighted.

A Clinical and Animal Experiment Integrated Platform for Small-Molecule Screening Reveals Potential Targets of Bioactive Compounds from a Herbal Prescription Based on the Therapeutic Efficacy of Yinchenhao Tang for Jaundice Syndrome

A herbal prescription in traditional Chinese medicine(TCM)has great complexity,with multiple components and multiple targets,making it extremely challenging to determine its bioactive compounds.Yinchenhao Tang(YCHT)has been extensively used for the treatment of jaundice disease.Although many studies have examined the efficacy and active ingredients of YCHT,there is still a lack of an in-depth systematic analysis of its effective components,mechanisms,and potential targets—especially one based on clinical patients.This study established an innovative strategy for discovering the potential targets and active compounds of YCHT based on an integrated clinical and animal experiment platform.The serum metabolic profiles and constituents of YCHT in vivo were determined by ultra-performance liquid chromatography–quadrupole time-of-flight mass spectrometry(UPLC-Q-ToF-MS)-based metabolomics combined with a serum pharmacochemistry method.Moreover,a compound–target–pathway network was constructed and analyzed by network pharmacology and ingenuity pathway analysis(IPA).We found that eight active components could modulate five key targets.These key targets were further verified by enzyme-linked immunosorbent assay(ELISA),which indicated that YCHT exerts therapeutic effects by targeting cholesterol 7a-hydroxylase(CYP7A1),multidrug-resistance-associated protein 2(ABCC2),multidrug-resistance-associated protein 3(ABCC3),uridine diphosphate glucuronosyl transferase 1A1(UGT1A1),and farnesoid X receptor(FXR),and by regulating metabolic pathways including primary bile acid biosynthesis,porphyrin and chlorophyll metabolism,and biliary secretion.Eight main effective compounds were discovered and correlated with the key targets and pathways.In this way,we demonstrate that this integrated strategy can be successfully applied for the effective discovery of the active compounds and therapeutic targets of an herbal prescription.

Metabolomics and Its Potential in Drug Discovery and Development From TCM

Metabolomics, an omic science in systems biology, is the comprehensive profiling of metabolic changes occurring in living systems and has been widely used in the modern research of traditional Chinese medicine(TCM). TCM is a complex medical science, which reflects rich philosophical dialectical thought, puts the human body into a large system for observation and keeps human in a healthy status. For TCM aroused great interest in the whole world, herbs and Chinese medical formulae(CMF) as treatment methods have also been widely attention.Metabolomics represents a powerful way that provides a dynamic drawing of the phenotype of biological systems via the research of endogenous metabolites, and its methods are similar to those of TCM. This review summarizes the advantages of metabolomics, highlight the key role of biomarkers for drug discovery and development of TCM.

Chinmedomics:Newer Theory and Application

The scientific interpretation of the effectiveness of traditional Chinese medicine（TCM） is a communication channel between Chinese medicine and modern medicine. The evaluation of TCM efficacy is an important prerequisite for discovering active constituents. Therefore, there is an urgent need to establish a biological language for scientific explanation of the effectiveness of TCM, and modern scientists can further accept the significant value of TCM theory and its clinical practice. The syndrome and corresponding formulation are two important parts in TCM, and they are directly related to the effectiveness of TCM. Our team has taken syndrome and formulation as the research objects, integrated serum pharm-chemistry of TCM with metabolomics technology, developed a new platform termed Chinmedomics, which is capable of evaluating effectiveness of TCM and discovering the syndrome biomarkers as well as the effective substances. The correlation between the endogenous biomarkers of syndrome and exogenous constituents of formulation is analyzed to find the highly associated compounds as the effective substances, and further clarifying their activities, and may discover lead compounds. This effective strategy could speed the drug discovery from natural resources. This article systematically introduced the establishment and application of Chinmedomics theory, in order to provide references for studies on TCM, and some characteristic examples are presented to highlight the application of this new strategy for discovering the potential active constituents of TCM.

Metabolomics Analysis of Health Functions of Physalis Pubescens L. using by Ultra-performance Liquid Chromatography/Electrospray Ionization Quadruple Time-of-Flight Mass Spectrometry

Herbal medicines may benefit from metabolomics studies, and applying metabolomics may provide answers about which herbal interventions may be effective for individuals, which metabolic processes are triggered, and the subsequent chemical pathways of activity. Physalis pubescens L(PPL) is an herbal fruit for one year living plant and has been developed into healthy function's food. However, the mechanisms of health functions are still unclear. To comprehensively and holistically assess its anti-fatigue and antioxidant effects, a novel integrative metabolomics approach was applied. In this study, we present metabolomics analysis applying ultra performance liquid chromatography coupled to quadrupole with time-of-flight mass spectrometry(UPLC-Q/TOF-MS) to determine metabolite alterations after oral administration PPL to rats. Fifteen metabolites in urine were identified as potential biomarkers. Pattern analysis of the UPLC-Q/TOF-MS data disclosed that PPL could relieve fatigue rats by ameliorating the disturbance in amino acids metabolism and energy metabolism, alleviating the oxidative stress from reactive oxygen species and the inflammatory damage, and recovering the destructed regulation. Based on these results, we demonstrated that PPL is a promising source of natural anti-fatigue and antioxidants material for use in functional foods and medicines.

Metabolomics Deciphering Therapeutic Effects and Mechanism of Traditional Chinese Medicines

Traditional Chinese medicine(TCM),an ancient medical system,has the advantages of multi-targeting and multi-ingredient preparations,and is different from modern pharmacology.However,because of the complexity of TCM and the limitation of present investigation method,the research for deciphering the scientific basis and systematic features of TCM is difficult to go further.Metabolomics has a significant increased study in recent years and enables mapping of early biochemical changes in disease and hence provides an opportunity to develop predictive biomarkers.Moreover,its method and design resemble those of traditional Chinese medicine.Therefore,it can provide useful tools for exploring essence of TCM,and will help to in-depth understand Chinese medicine syndromes.In this mini-paper,particular attention will be paid to the past successes in applications of robust metabolomics to contribute to small metabolites discovery in TCM development.

Panax Notoginseng Saponins Increases the Blood Concentration of Nifedipine by Inhibiting CYP3A4 Enzyme through PXR-and CAR-Mediated Pathway

Objective:To explore the mechanism underlying the effect of Panax notoginseng saponins(PNS)on the pharmacokinetics of nifedipine(NF)in rats.Materials and Methods:Twenty-four rats were randomly divided into blank(BL)group,PNS group,NF group,and PNS+NF group,with six rats in each group.Noncompartmental analysis and t-test were carried out to determine the difference between the pharmacokinetic parameters of NF in different groups.CYP3 A4 enzyme activity was calculated using the probe drug method.The mRNA and protein contents of CYP3 A4,nuclear receptor CAR,and PXR in rat liver were quantitatively analyzed by qRT-PCR and Western blot.Results:After the rats were treated with the combination of PNS and NF,the plasma concentration,half-life,peak time,and area under the concentration-time curve of NF increased,whereas the clearance rate decreased.The inhibitory effect on CYP3 A4 enzyme activity was in the following order:PNS+NF group(strongest)>PNS group>NF group,and BL group(weakest).Similar changes were observed for the inhibitory effect on CYP3 A4,CAR,and PXR mRNA and protein content,and the order was as follows:PNS+NF group(weakest)<PNS group<NF group,and BL group(strongest).Conclusion:In combination with NF,PNS may inhibit the mRNA and protein expression of nuclear receptor CAR and PXR and the activity of CYP3 A4 enzyme,slowing down the pharmacokinetics of NF in rats,increasing its blood concentration,and enhancing the therapeutic effect of NF.

Pharmacokinetics Applications of Traditional Chinese Medicines

Traditional Chinese medicine(TCM) has been widely used in many oriental countries for thousands of years and played an indispensable role in the prevention and treatment of diseases, especially the complicated and chronic ones. It is a very complex mixture containing hundreds or thousands of different components. Pharmacokinetic study on active constituents in TCM preparations is a good way for us to explain and predict a variety of events related to the efficacy and toxicity of TCM. In the drug discovery phases, pharmacokinetics is a key to guide medicinal chemists in the optimization process of a chemical series and to assist pharmacologists to design in vivo studies.To explore the potentially bioactive components in TCM, it is necessary to further study the in vivo pharmacokinetic characteristics of multiple absorbed components and find out the optical time-course behavior to providing more substantial research for new leads in drug discovery. Pharmacokinetics screening method could provide a reliable means of prospecting natural products in the search for new leads in drug discovery. This review summarizes the research progress of PK on TCM in the search for suitable lead compounds in recent years.