- Open Access
Application of metabolomics in viral pneumonia treatment with traditional Chinese medicine
- Lili Lin†1, 2,
- Hua Yan†1, 2,
- Jiabin Chen3,
- Huihui Xie3,
- Linxiu Peng4,
- Tong Xie1, 2,
- Xia Zhao1, 2,
- Shouchuan Wang1, 2 and
- Jinjun Shan1, 2Email authorView ORCID ID profile
© The Author(s) 2019
- Received: 3 December 2018
- Accepted: 5 March 2019
- Published: 12 March 2019
Nowadays, traditional Chinese medicines (TCMs) have been reported to provide reliable therapies for viral pneumonia, but the therapeutic mechanism remains unknown. As a systemic approach, metabolomics provides an opportunity to clarify the action mechanism of TCMs, TCM syndromes or after TCM treatment. This review aims to provide the metabolomics evidence available on TCM-based therapeutic measures against viral pneumonia. Metabolomics has been gradually applied to the efficacy evaluation of TCMs in treatment of viral pneumonia and the metabolomics analysis exhibits a systemic metabolic shift in lipid, amino acids, and energy metabolism. Currently, most studies of TCM in treatment of viral pneumonia are untargeted metabolomics and further validations on targeted metabolomics should be carried out together with molecular biology technologies.
Pneumonia is the world’s leading cause of death in young children and elderly people. Many pathogens are associated with pneumonia, and now attention is turning to the importance of viruses as pathogens . In western medicine, viral pneumonia is defined as a disease in which there are gas exchange abnormalities at the alveolar level accompanied by inflammation of the lung parenchyma . While, in the theoretical system of traditional Chinese medicine (TCM), the etiologies of this disease are classified into external and internal causes. Exterior pathogenic “wind and heat” invades the weak lung (interior cause) through the skin, mouth or nose, causing lung qi obstruction and stagnation. The main pathological products are phlegm, heat and blood stasis, manifesting with fever, cough, dyspnea, wheezing, nasal flaring, etc. The basic treatment principles are to regulate the lung qi, resolve phlegm, and relieve cough and dyspnea. The TCM prescriptions is composed of various kinds of medicinal plants, animals and minerals in the form of oral liquid, powder and granules.
According to the TCM treatment principle, traditional Chinese medicines (TCMs) have been reported to cure viral pneumonia in lots of ancient literature and modern research [3–7]. Our research group has been engaged in TCM treatment of children with viral pneumonia for nearly 20 years. Jinxin oral liquid (JOL), modified from ma-xing-shi-gan decotion, is proved to have good treatment effects both in clinic and experimental studies . Although, TCMs in treatment of viral pneumonia have achieved certain therapeutic effects, the mechanism of TCMs remains unclear.
Omics technologies, which system biology bring, are valuable tools for TCM research. Metabolomics belongs to system biology and omics, is a new logical approach to search for functional small-molecules to evaluate the pharmacological effect of TCMs [9–11]. In recent years, our research group has conducted a series of metabolomics research to examine the effect of TCMs in treatment of viral pneumonia [12–15]. In this review, we try to do the summary of recent metabolomics research and seek more evidences for the reliability of TCM in treatment of in viral pneumonia.
Increasing results have highlighted the usefulness of metabolomics as a promising laboratory tool for discriminating different chronic lymphocytic leukemia molecular subgroups  and discovering biomarkers for coronary artery disease progression . The application of metabolomics to the prediction of the specific patient response to drug treatments is termed pharmacometabolomics, it is more closely associated to a patient´s pharmacological phenotype and could be more informative than genomic or proteomic data when trying to understand the mechanisms of inter-patient variability in response to drug therapy [33–35].
Examples that have emerged in the last few years demonstrating the potential of metabolomics tools and data in preclinical and clinical development. The study of metabolomics can potentially provide useful information for the diagnosis and prognosis of patients as well as for predicting pharmacological responses to specific interventions. Furthermore, specific metabolic signatures occur after drug treatment, thus providing information from pathways targeted or affected by drug therapy . Thus, metabolomics, as a kind of logical strategy, is needed to achieve the goal of precision medicine.
Entering 21st century, TCM as a holistic approach that attempts to balance the body, mind and spirit in individuals with the environment, is getting more and more popular in the whole world . However, the development of TCM also faces severe challenges and suffers from insufficient modern evidences owing to lack of scientific and technologic approaches. Fortunately, the property of metabolomics consists with the holistic thinking of TCM. Metabolomics may beneficially provide an opportunity to clarify the action mechanism of TCM and the meaning of evidence-based TCM by developing the systematic analysis of the metabolites and discovering various biomarkers and perturbed pathways on TCM syndromes or after TCM treatment.
In recent years, metabolomics has been gradually applied to research in the area of TCM and try to highlight the key role of metabolomics to resolve TCM issues. It may scientifically express the meaning of TCM syndromes and the efficacy of TCM treatment [47–49]. For example, based on GC–MS, a research group in China has established a rat model of myocardial ischemia with blood stasis syndrome and qi-yin deficiency syndrome. The endogenous metabolites in plasma were analyzed, and the metabolic profiles between the two TCM syndromes and normal rats were found to be significantly different . A research group carried out a comprehensive analysis of metabolic patterns of typical Jaundice syndrome (JS) and sub-types. They have identified 44 metabolites in JS. The most altered functional pathway was glutamate metabolism, synthesis, and degradation of ketone bodies, alanine and aspartate metabolism (Fig. 2). The results suggested that metabolomics method would be helpful to establishing a suitable model for reasonably evaluating disease syndrome, exploring pathological mechanism of the syndrome, clarifying the relationships between the syndrome and related diseases .
Wang et al. evaluated metabolomic characters of the hepatotoxicity induced by alcohol and the intervention effects of Yin Chen Hao Tang (YCHT), a classic traditional Chinese medicine formula composed of Flos Artemisiae, Gardeniae Jasminoidis, Fructus and Radix et Rhizoma Rhei for treatment of jaundice and liver disorders in China. The greatest difference in metabolic profiling was observed from alcohol-treated rats compared with the YCHT-treated rats . In Table 2, we summarized a kind of potential anti-virus compound-Baicalein synthesized from Scutellaria baicalensis Georgi, reported to be used in China for treating RSV pneumonia . In Table 3, anti-viral herbs and formulas were selected that have metabolomics evidences in treatment of viral pneumonia. These simple studies above demonstrated that metabonomics, one of the most important systems biology platforms, showed a potential for identifying and characterizing biochemical responses of organism to TCMs. Meanwhile, this strategy offered a practical method for performing intervened assessments of TCM in the future.
Metabolomics, as a systemic approach, is a “top-down” strategy to reflect the function of living organisms from the end products of the metabolic network . It will also help to understand the metabolic changes of a complete system under different kinds of physiological and pathological conditions. This property of metabolomics agrees with the holistic thinking of TCMs, suggesting it has the potential to improve our understanding of the theory behind the evidence-based TCM. This review revealed that many of the important information like TCMs preparation, part used, TCMs-derived active compounds, TCMs including aqueous extracts and traditional Chinese medical formulas (or patent medicines) in treatment of viral pneumonia.
From metabolomics research that has been conducted in this review, we can see that all the significant pathways (Fig. 2) in viral pneumonia are related to tricarboxylic acid cycle (TCA). Amino acids are active biomarkers in those pathways, including tryptophan metabolism, alanine, aspartate and glutamate metabolism, arginine and proline metabolism, d-glutamine and d-glutamate metabolism, phenylalanine metabolism, glycine, serine and threonine metabolism, valine, leucine and isoleucine biosynthesis, cysteine and methionine metabolism, vitamin B6 metabolism. Nucleotides, The products of amino acids, also contribute greatly to TCA. Nucleotides metabolism is composed of purine metabolism, pyrimidine metabolism, glutathione metabolism. Based on our previous research, arachidonic acid, fatty acid and lipid metabolism is turning to take the leading role in TCMs treatment of viral pneumonia. Currently, most studies of TCM in treatment of viral pneumonia are untargeted metabolomics and further validations should focus on targeted metabolomics combined with molecular biology technologies.
Metabolomics is going to be a powerful approach to support TCM research in the future. However, the issues and future directions of using metabolomics in TCM studies should be pointed out. The current metabolomics technologies in research on TCM is still in its infancy due to its chemical nature of multi-component mixtures that often possess their own inherent holistic bioactivities. We also highlight the potential role of metabolomics technologies in evidence-based studies of TCM disease-syndrome combination models. Very limited number of metabolomics research provides toxic profile of TCMs, metabolomics toxicity studies should be carried out for TCMs in animal system to establish a safe dose range and specific adverse effect. Further metabolomics-pharmacological research is required to promote the traditional knowledge of TCM and take it to the light of science.
Based on the contributions, LL and HY are listed as the first authors while JS is the correspondence. JS, LL, HY, XZ and SW conceived, designed the study and drafted the manuscript. JC, HX and TX were major contributors in reviewing the manuscript. All authors read and approved the final manuscript.
We want to thank all the members and students from the laboratory of Jiangsu Key Laboratory of Pediatric Respiratory Disease, Nanjing University of Chinese medicine.
The authors declare that they have no competing interests.
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Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.
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This work was supported by the National Natural Science Foundation of China (81774156, 81704118, 81373688); the Natural Science Foundation of Jiangsu Province (BK20161573, BK20151004); the Major Research Plan of Natural Science Foundation of the Higher Education Institutions of Jiangsu Province (16KJA360002, 17KJB360007); Jiangsu Provincial 333 High Levels Talents Cultivation Project (BRA2016427); Jiangsu Provincial Six Talent Peaks Project (YY-022); the Project of the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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