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Application of Metabolomics in Viral Pneumonia

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Application of Metabolomics in Viral Pneumonia Lin et al. Chin Med (2019) 14:8 https://doi.org/10.1186/s13020-019-0229-x Chinese Medicine REVIEW Open Access Application of metabolomics in viral pneumonia treatment with traditional Chinese medicine Lili Lin1,2†, Hua Yan1,2†, Jiabin Chen3, Huihui Xie3, Linxiu Peng4, Tong Xie1,2, Xia Zhao1,2, Shouchuan Wang1,2 and Jinjun Shan1,2* Abstract Nowadays, traditional Chinese medicines (TCMs) have been reported to provide reliable therapies for viral pneumo- nia, but the therapeutic mechanism remains unknown. As a systemic approach, metabolomics provides an oppor- tunity 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 efcacy 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. Keywords: TCM, Treatment, Metabolomics, Virus, Pneumonia Introduction etc. Te basic treatment principles are to regulate the Pneumonia is the world’s leading cause of death in young lung qi, resolve phlegm, and relieve cough and dyspnea. children and elderly people. Many pathogens are asso- Te TCM prescriptions is composed of various kinds of ciated with pneumonia, and now attention is turning medicinal plants, animals and minerals in the form of to the importance of viruses as pathogens [1]. In west- oral liquid, powder and granules. ern medicine, viral pneumonia is defned as a disease in According to the TCM treatment principle, traditional which there are gas exchange abnormalities at the alveo- Chinese medicines (TCMs) have been reported to cure lar level accompanied by infammation of the lung paren- viral pneumonia in lots of ancient literature and modern chyma [2]. While, in the theoretical system of traditional research [3–7]. Our research group has been engaged Chinese medicine (TCM), the etiologies of this disease in TCM treatment of children with viral pneumonia for are classifed into external and internal causes. Exterior nearly 20 years. Jinxin oral liquid (JOL), modifed from pathogenic “wind and heat” invades the weak lung (inte- ma-xing-shi-gan decotion, is proved to have good treat- rior cause) through the skin, mouth or nose, causing lung ment efects both in clinic and experimental studies [8]. qi obstruction and stagnation. Te main pathological Although, TCMs in treatment of viral pneumonia have products are phlegm, heat and blood stasis, manifest- achieved certain therapeutic efects, the mechanism of ing with fever, cough, dyspnea, wheezing, nasal faring, TCMs remains unclear. Omics technologies, which system biology bring, are valuable tools for TCM research. Metabolomics belongs *Correspondence: [email protected] to system biology and omics, is a new logical approach †Lili Lin and Hua Yan contributed equally to this work 1 Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute to search for functional small-molecules to evaluate of Pediatrics, Afliated Hospital of Nanjing University of Chinese Medicine, the pharmacological efect of TCMs [9–11]. In recent No. 138, Xianlin Avenue, Qixia District, Nanjing 210023, China years, our research group has conducted a series of Full list of author information is available at the end of the article © The Author(s) 2019. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creat iveco mmons .org/licen ses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creat iveco mmons .org/ publi cdoma in/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Lin et al. Chin Med (2019) 14:8 Page 2 of 11 metabolomics research to examine the efect of TCMs in multiple antiviral mechanisms and synergizing with IFN treatment of viral pneumonia [12–15]. In this review, we in promoting antiviral activities [23]. try to do the summary of recent metabolomics research and seek more evidences for the reliability of TCM in Metabolomics applications in precision medicine treatment of in viral pneumonia. Metabolomics is the systematic study of the meta- bolic profle that specifc cellular processes leave Traditional Chinese Medicines (TCMs) and its behind, including cells, tissues, and body fuids [24]. application in viral pneumonia Te metabolic profle provides a quantifable readout TCMs have been reported to provide reliable therapy for of biochemical state from normal physiology to diverse almost 2500 years. Nowadays, TCMs are widely used for pathophysiologies in a manner that is often not obvious prevention and treatment of viral pneumonia in China from gene or protein levels [25]. Mass spectrometry (MS) and many other Asian countries [16]. Te most com- combined with softwares or platforms (Fig. 1), such as monly used anti-virus substances in TCMs are plant MetaboAnalyst 4.0 (https ://www.metab oanal yst.ca) [26], elements, such as root, rhizome, leaf, fower, fruit, seed, XCMS [27] and MS-DIAL [28], are efective tools for etc. Other non-botanic substances including animal metabolite separation and collecting the information of and mineral products are also utilized [17]. Anti-virus the molecular composition of samples [29, 30], which will TCM formulas originate from the profound experiences greatly facilitate the interpretation of the metabolomics of practitioners with understanding of ancient Chinese data. medicine theories, and the methods of application have Increasing results have highlighted the usefulness of been passed down through oral history. metabolomics as a promising laboratory tool for dis- In recent research, TCMs were reported to boost criminating diferent chronic lymphocytic leukemia body resistance against virus by modulating the immune molecular subgroups [31] and discovering biomarkers response [17–20]. Many viruses have established sophis- for coronary artery disease progression [32]. Te appli- ticated mechanisms to interact with the host immune cation of metabolomics to the prediction of the specifc system. TCMs have been shown to enhance antibody patient response to drug treatments is termed pharmaco- production, T cell proliferation, the expression of anti- metabolomics, it is more closely associated to a patient´s gen specifc CD4 + and CD8 + responses, and increase of pharmacological phenotype and could be more informa- the titers of IgG1, IgG2, and IgA. Along with the func- tive than genomic or proteomic data when trying to tion to increase levels of T1 type cytokine secretion understand the mechanisms of inter-patient variability in and activation of alveolar macrophages, suppress T2/ response to drug therapy [33–35]. T17-responses, and maintain the balance between T1 Examples that have emerged in the last few years dem- and T2/T17 cells for the prevention of viral pneumonia onstrating the potential of metabolomics tools and data [21]. in preclinical and clinical development. Te study of In addition, an increasing number of TCMs-derived metabolomics can potentially provide useful informa- active compounds, TCM herbs and formulas with direct tion for the diagnosis and prognosis of patients as well antiviral activity are garnering evidence of experimental as for predicting pharmacological responses to specifc efcacy. TCMs can efectively inhibit viral attachment interventions. Furthermore, specifc metabolic signa- and cell internalization, in order to minimize the viral tures occur after drug treatment, thus providing informa- spread and replication. According to the literature and tion from pathways targeted or afected by drug therapy our previous research, resveratrol and baicalin exhibited [36]. Tus, metabolomics, as a kind of logical strategy, is certain antiviral activity against viruses in both plaque needed to achieve the goal of precision medicine. assay and mouse models [22]. Taking Jin Xin oral liquid and Qing Fei oral liquid as examples of patent medi- Metabolomics from precision medicine to viral cines [8], they have been proved to inhibit infammation, pneumonia reduce viral replication and viral load in the lung tissues. Many microorganisms are associated with pneumo- Along with direct antiviral activity, TCMs could be ben- nia, and now attention is turning to the importance of efcial in preventing viral infection due to its immune- viruses as pathogens [1]. Te most commonly identifed modulatory efect, producing of IFN- and TNF-. Both agents of viral pneumonia in children were respiratory IFN- and TNF- belong to type I interferon (IFN), which syncytial virus (RSV, 11%), infuenza viruses (IFV, 10%), contribute to the innate immunity against viral infec- parainfuenza viruses (PIV, 8%) and adenovirus (ADV, tion. More attention should be paid to type I interferon 3%) [37, 38]. With a full set of tests in adults, fndings (IFN) signaling pathway, for its good efcacy in triggering of three reports suggested that a third of adult cases of pneumonia were associated with viral infection [39–41]. Lin et al. Chin Med (2019) 14:8
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