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.
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.
Chuanwu(CW), a famous traditional Chinese medicine(TCM) from the mother roots of Aconitum carmichaelii Debx..(Ranunculaceae), has been used for the treatment of various diseases. Unfortunately, its toxicity is frequently reported because of its narrow therapeutic window. In the present study, a metabolomic method was performed to characterize the phenotypically biochemical perturbations and potential mechanisms of CW-induced toxicity. Meanwhile, the expression level of toxicity biomarkers in the urine were analyzed to evaluate the detoxification by combination with Gancao(Radix Glyeyrrhizae, CG), Baishao(Radix Paeoniae Alba, CS) and Ganjiang(Rhizoma Zingiberis, CJ), which were screened from classical TCM prescriptions. Urinary metabolomics was performed by UPLC-Q-TOF-HDMS, and the mass spectra signals of the detected metabolites were systematically analyzed using pattern recognition methods. As a result, seventeen biomarkers associated with CW toxicity were identified, which were associated with pentose and glucuronate interconversions, alanine, aspartate, and glutamate metabolism, among others. The expression levels of most toxicity biomarkers were effectively modulated towards the normal range by the compatibility drugs. It indicated that the three compatibility drugs could effectively detoxify CW. In summary, our work demonstrated that metabolomics was vitally significant to evaluation of toxicity and finding detoxification methods for TCM.
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.
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.
Wei-Wei MaAi-Hua ZhangHui SunXiang-Cai MengXi-Jun Wang
Metabolic abnormalities lead to the dysfunction of metabolic pathways and metabolite accumulation or deficiency which is wellrecognizedhallmarks of diseases. Metabolite signatures that have close proximity to subject’s phenotypic informative dimension,are useful for predicting diagnosis and prognosis of diseases as well as monitoring treatments. The lack of early biomarkers couldlead to poor diagnosis and serious outcomes. Therefore, noninvasive diagnosis and monitoring methods with high specificity andselectivity are desperately needed. Small molecule metabolites-based metabolomics has become a specialized tool for metabolicbiomarker and pathway analysis, for revealing possible mechanisms of human various diseases and deciphering therapeuticpotentials. It could help identify functional biomarkers related to phenotypic variation and delineate biochemical pathwayschanges as early indicators of pathological dysfunction and damage prior to disease development. Recently, scientists haveestablished a large number of metabolic profiles to reveal the underlying mechanisms and metabolic networks for therapeutictarget exploration in biomedicine. This review summarized the metabolic analysis on the potential value of small-moleculecandidate metabolites as biomarkers with clinical events, which may lead to better diagnosis, prognosis, drug screening andtreatment. We also discuss challenges that need to be addressed to fuel the next wave of breakthroughs.
Shi QiuYing CaiHong YaoChunsheng LinYiqiang XieSongqi TangAihua Zhang
Elucidation of the efficacy of traditional Chinese medicine(TCM) is of importance for scientists of modern medicine to understand the value of TCM clinical experience, and it is necessary to have a biological language to scientifically describe the efficacy of TCM. With this background,Chinmedomics has been proposed by our team, which includes integrating serum pharmacochemistry and metabolomics technology, defining theory and research methods for expressing the efficacy of TCMs based on the biomarkers discovery of TCM syndrome and elucidating the efficacy of TCM formulae, discovering effective constituents, and finally elucidating the scientific value of TCM. In the present study, the innovative chinmedomics strategy was conducted to evaluate the therapeutic effects of Shen Qi Wan(SQW) acting on Shen Yang Xu(kidney-yang deficiency syndrome, KYDS). We analyzed the urine metabolic trajectory between the model and control groups, and identified the biomarkers by the multivariate analysis. We found that SQW caused significant restoration of abnormal metabolism of KYDs. Using the method of metabolomics, 17 potential urine biomarkers were analyzed through 4 repeated tests in our serial studies on SQW and KYDS. Under the premise of therapeutic efficacy, a total of 56 peaks were tentatively characterized in vivo by the use of serum pharmacochemistry. Correlation analysis between marker metabolites and in vivo constituents of SQW showed that 28 compositions had a close relationship with urine biomarkers of therapeutic effects, whichmight play a key role in the therapeutic effect of SQW. These compounds were imported into an online database to predict their targets. Twenty-three important potential targets were identified, which were related to the metabolism of steroid hormone, tryptophan utilization, and thyroid hormone. In conclusion, chinmedomics is a useful strategy for discovery of potentially effective constituents from complex TCM formulae.
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.
Hang ChuHui SunGuang-Li YanAi-Hua ZhangChang LiuHui DongXiang-Cai MengXi-Jun Wang
