DNAMicroarray-BasedScreeningand CharacterizationofTraditionalChineseMedicine.

Abstract. Influenza, because of its virus is highly contagious and easy to mutate, has caused many outbreaks around the world. Traditional Chinese medicine (TCM) has been used in China for the prevention and treatment of influenza since ancient times, and now more and more people choose to use TCMs to prevent and treat influenza in their daily life. At present, researchers have also tried to study the mechanism of action of TCMs against influenza virus from multiple angles, but there are still many problems in the existing research that deserve further improvement. This article summarizes the researches on the mechanism of action of various TCMs against influenza virus by researchers at home and abroad in recent years and divides the mechanism of action of TCM against influenza virus, which according to the pathogenic mechanism of influenza virus, into two categories: direct inhibition and indirect inhibition. At the same time, this article found that many TCMs can also reduce the damage caused by viral infections by inhibiting the body's excessive immune response. This article also found that there are still some problems in the current research, such as unclear active ingredients, unclear effective dosage, lack of clinical trials, lack of comparative experiments between Chinese and Western medicines, and lack of research on influenza virus B, etc., which are hoped to be focused on in the future researches.

There is no doubt that the traditional Chinese medicine(TCM) is effective, practical and scientific after it was used for thousands of years. However, the mechanisms of action of many TCM are still unclear because of their multi-component, multi-target and multi-level features, which hinder the modernization and internationalization of the TCM. Proteomics is to analyze the composition and activity of intracellular proteins which are changing dynamically from a holistic perspective. It is consistent with the holistic and dynamic views of the TCM and brings about the hope of clarifying the mechanism of action of the TCM. In recent years, great progress has been made in the application of proteomics to determine the mechanism of the TCM. This article introduced the core technologies of proteomics and systematically summarized the applications of proteomics in the study of the mechanism of the Chinese medicinal formulae, single Chinese medicine and monomeric compounds from the TCM to provide innovative ideas and methods for reference.

Traditional Chinese medicine(TCM) has been treating diseases for thousands of years and still holds an irreplaceable position in modern disease treatment. The composition of TCM is complex, and its mode of action features multi-pathway and multi-target characteristics, making its pharmacological actions and mechanisms complicated. The principles and mechanisms of TCM have always been a hot topic among scholars from various fields. Increasingly, studies show that indirect action plays an important role in the mode of action of TCM. The gut microbiota is regarded as a new invisible metabolic organ, and TCM can treat diseases by targeting the gut microbiota, thereby exerting an indirect effect across organs based on the connection between organs. Therefore, this paper summarized the indirect regulatory mechanisms of TCM based on the visceral manifestation theory and the organ axis of modern medical research. It also discussed the talks and communication mechanisms between the gut microbiota and target organs such as the liver, brain, kidney, and lungs, providing references for research on the mechanisms of indirect action of TCM and the development of innovative drugs.

Prediction of quality markers of traditional Chinese medicines based on network pharmacology

The research and development of new traditional Chinese medicine drugs has gradually formed a new system based on the combination of traditional Chinese medicine theory, human experience, and clinical trials(referred to as the "three combinations"). However, given the characteristics of traditional Chinese medicine's "syndrome differentiation and treatment" and "diverse components and complex mechanisms", there are still problems in the current research and development of new traditional Chinese medicine drugs, such as insufficient research on the material basis and overall mechanism of action, and incomplete evidence chain system. At the same time, there are still many challenges in collecting human experience, evaluating clinical efficacy, and controlling the quality of active ingredients, which restrict the innovation process of research and development of new traditional Chinese medicine drugs. Network pharmacology, based on the core theory of "network targets", breaks through the limitations of the traditional "single target" reduction analysis research model, emphasizing the comprehensive effects of disease or syndrome biological networks as targets to characterize the overall regulatory mechanism of traditional Chinese medicine prescriptions. This is in line with the idea of the holistic view of traditional Chinese medicine, providing a new method consistent with the holistic view of traditional Chinese medicine for studying the complex mechanism of action of traditional Chinese medicine and the development of new traditional Chinese medicine drugs. It is internationally recognized as a "next generation of drug research model". In order to promote the research of new tools, methods, and standards for the evaluation of traditional Chinese medicine, and to break through the fundamental, critical, and cutting-edge technical challenges in the field of traditional Chinese medicine regulation, this consensus aims to explore the characteristics, progress, challenges, applicable paths, and specific application situations of network pharmacology as a new theory, method, and tool applied to the research and development of new traditional Chinese medicine drugs, in order to improve the quality of research and development of new traditional Chinese medicine drugs and accelerate the efficiency of research and development of new traditional Chinese medicine products.

The efficacy of traditional medicine such as traditional Chinese medicine (TCM) had been confirmed by many years of clinical use. However, the mechanisms of traditional medicine remained obscure. Since the development of systems biology in 2000, systems biology technologies have been popularly used in the mechanism study of traditional medicine. In this special issue, we particularly picked reviews and research papers related to mechanism study of TCM, TCM diagnosis, or TCM therapy methods using proteomics as well as other systems biology technologies. There are 10 papers collected in this special issue, in which 3 papers are reviews and 7 papers are original research papers. The 3 reviews in the present issue introduce the advancements in applications of proteomics technologies in the study of TCM and the achievements in the mechanism study of TCM. Q. Ji et al. summarized the applications of proteomics technologies in TCM syndrome research as well as the mechanistic study of TCM treatments, including Chinese herbal medicine, Chinese herbal formula, and acupuncture. Furthermore, they introduced the combined analyses of proteomics with other “-omics” technologies in the study of TCM. Y. A. Sulistio and K. Heese discussed the utility of comparative proteomics for a better understanding of the mechanisms involved in TCM activities and its potential application as complementary therapy for the treatment of Alzheimer's disease (AD). Additionally, they reviewed the data from comparative proteomics studies of AD patients and established the relevance of the data with available AD hypotheses and potential TCM-based treatments, most notably regarding the ubiquitin proteasome system. Y. Yang et al. focused on discussing various results of proteomics studies of mechanisms of anticancer TCM, including terpenes, flavonoids, and glycosides. And they suggested future research strategies such as integrating translating mRNA analysis with proteomics in the study of the mechanisms of anticancer TCM. Four of the research papers reported results of mechanism studies of TCM. J.-Y. Shiau et al. studied the mechanism of 2-β-D-glucopyranosyloxy-1-hydroxytrideca-5,7,9,11-tetrayne, an active component of Bidens pilosa, in human T-cell acute lymphocytic leukemia cells by using combined differential proteomics and bioinformatics approaches. M.-N. Shi et al. reported the protective effects of scutellarin, a flavone isolated from Erigeron breviscapus (Vant.) Hand.-Mazz, on human cardiac microvascular endothelial cells against hypoxia-reoxygenation injury. Possible target-related proteins of scutellarin were searched using proteomics analysis and a possible interaction network was predicted using bioinformatics analysis. C.-C. Guo et al. studied the antiosteoporotic effects and possible target-related proteins of Huangqi Sanxian decoction, a traditional Chinese formula composed of Radix astragali, Epimedii folium, Cistanche herba, Radix notoginseng, Radix Salviae Miltiorrhiae, Corydalis rhizoma, Radix Angelicae sinensis, and Radix Clematidis, in cultured rat osteoblasts. Z. Bo et al. investigated the molecular mechanism of fibroblast regulation and the treatment of recurrent oral ulcer by Shuizhongcao granule-containing serum. Shuizhongcao granule is a TCM formula composed of buffalo horn, urine sediment, callicarpa, and so forth, and it exhibited great efficacy in the clinical treatment of recurrent oral ulcer. In the present issue, there are also 3 research papers reporting about the mechanisms of TCM used for the diagnosis of diseases or specialized TCM therapy methods such as moxibustion. In the TCM system, tongue diagnosis has been an important diagnostic method. X. Liu et al. used the GC/MS technology to determine the potential changes of metabolites and identify special metabolic biomarkers in the tongue coating of H. pylori infected chronic gastritis patients. W.-T. Dang et al. studied the expression of caspase-1 gene transcript variant mRNA in peripheral blood mononuclear cells of patients with primary gout in different TCM syndromes. X.-L. Shi et al. investigated the effects of moxibustion, a traditional Chinese practice that involves heated Artemisia vulgaris (mugwort) stimulation, on hormonal imbalance and ovarian granulosa cell apoptosis in a rat model of perimenopause. In summary, this special issue provides a snapshot of the current status of mechanism studies of traditional medicine, especially TCM, using proteomics and other systems biology technologies. Authors of the present issue highlight both the achievements and challenges faced in the field of the mechanism study of traditional medicine. Hopefully, this publication will help readers to follow mechanism studies of traditional medicine and will contribute to improved applications of proteomics or other systems biology technologies in research of traditional medicine.

The biological targets of traditional Chinese medicine (TCM) are the core effectors mediating the interaction between TCM and the human body. Identification of TCM targets is essential to elucidate the chemical basis and mechanisms of TCM for treating diseases. Given the chemical complexity of TCM, both in silico high-throughput compound-target interaction predicting models and biological profile-based methods have been commonly applied for identifying TCM targets based on the structural information of TCM chemical components and biological information, respectively. However, the existing methods lack the integration of TCM chemical and biological information, resulting in difficulty in the systematic discovery of TCM action pathways. To solve this problem, we propose a novel target identification model NP-TCMtarget to explore the TCM target path by combining the overall chemical and biological profiles. First, NP-TCMtarget infers TCM effect targets by calculating associations between herb/disease inducible gene expression profiles and specific gene signatures for 8233 targets. Then, NP-TCMtarget utilizes a constructed binary classification model to predict binding targets of herbal ingredients. Finally, we can distinguish TCM direct and indirect targets by comparing the effect targets and binding targets to establish the action pathways of herbal component-direct target-indirect target by mapping TCM targets in the biological molecular network. We apply NP-TCMtarget to the formula XiaoKeAn to demonstrate the power of revealing the action pathways of herbal formula. We expect that this novel model could provide a systematic framework for exploring the molecular mechanisms of TCM at the target level. NP-TCMtarget is available at http://www.bcxnfz.top/NP-TCMtarget.

As a natural antioxidant resource, traditional Chinese medicine (TCM) has been paid much more attentions than before. The studies on its antioxidative activity have also increased dramatically in recent years. Abundant studies on TCM show that some TCM can increase body's activity of antioxidant enzymes, enhance body's ability of scavenging free radicals and decrease the generation of lipid peroxide (LPO) and malondialdehyde (MDA) in the body etc. The action mechanism of TCM is closely related to its active constituents, including polysaccharides, quinines, flavonoids, saponins, alkaloids, terpenes, phenolic acids compounds and tannins etc. Through referring to related reports on TCM, in the last 20 years, this paper reviews literatures involved in antioxidation research on TCM. Antioxidative mechanism, functional property and application prospect of some active constituents with antioxidation in TCM are discussed.

Potential activity of Traditional Chinese Medicine against Ulcerative colitis: A review

Network pharmacology was rapidly developed based on multidisciplinary holistic analysis of biological systems, which has become a popular tool in traditional Chinese medicine (TCM) research in recent years. Its characteristics of integrity and systematization provide a new approach for the study on complex TCM systems, which has many similarities with the holistic concept of TCM. It has been widely used to explain the mechanism of TCM treatment of diseases, drug repositioning, and interpretation of compatibility of TCM prescriptions, to promote the modernization of TCM. The use of TCM have provided crucial support on prevention and treatment of diseases such as the famous “three medicines and three prescriptions”. Furthermore, TCM has become an important part of the treatment of COVID-19 and is one of the main contents of the “Chinese plan” to fight the epidemic. The current review demonstrated the role of TCM in treating diseases with multiple components, multiple targets, and multiple pathways, interprets the connotation of TCM treatment method selection based on pathogenesis and also discusses the application of network pharmacology in the study of COVID-19 treatment in TCM including single drug and prescription. However, there are still some shortcomings such as the lack of experimental verification and regular upgrading of the TCM pharmacology network. Therefore, we must pay attention to the characteristics of TCM and develop a network pharmacology method suitable for TCM system research when applying network pharmacology to TCM research.

Prolyl hydroxylase domain 2 (PHD2) is a key enzyme regulating the expression of hypoxia inducible factor (HIF). Its inhibitors can improve the expression of HIF and downstream genes, which can treat hypoxia-related diseases. Therefore, the establishment of a reliable PHD2 inhibitors screening method is of great significance for the drug development of hypoxia-related diseases. In this work, an accurate, rapid, and simple screening method for PHD2 inhibitors was introduced by capillary zone electrophoresis (CZE). In order to improve the detection sensitivity, the derivative reaction of α-ketoglutaric acid (α-OG) and 1,2-diaminobenzene (OPD) was used to enhance the UV absorption of α-OG (the substrate in the enzymatic reaction). The CZE method selected 20mM Na2 B4 O7 buffer (pH9.0) as the separation buffer, +25kV as the separation voltage, 25°Cas the cartridge temperature, and 210nm as the detection wavelength. Under this condition, the analysis of a single sample can be realized within 9min. Compared with the existing reported methods, the present work can directly screen the PHD2 inhibitory activity of traditional Chinese medicine (TCM) extracts, which is of significance for the target-purification of bioactive individual compounds from TCMs. Under the optimal conditions, the PHD2 inhibitor screening platform was successfully established, and it was found that 70% methanol/water extracts of Astragali Radix and Codonopsis pilosula had good PHD2 inhibitory activity. Furthermore, the present work provides a novel approach for screening the PHD2 inhibitory activity of TCM extracts and the discovery of anti-hypoxia bioactive compounds.

Application of proteomics to determine the mechanism of action of traditional Chinese medicine remedies

To analyze the intersections among the western medicine action network for preventing and treating coronary heart disease (CHD), as well as traditional Chinese medicine (TCM) action network for activating blood and dissolving stasis. In this article, 11 characteristic parameter values of network nodes, including connectivity, bottleneck, betweenness, were calculated. The target identification model was established based on key node characteristic parameters in the CHD-western medicine intersection network with support vector machine. Its C and y parameters were 5.14 and--1.11, respectively, with the predicted accuracies for positive and negative samples of 81.6% and 79.2%. The predicted sensitivity, specificity and accuracy of the test set samples were 81.5%, 78.3% and 79.6%, respectively. Besides, the model was applied to predict potential action targets of the CHD-activating blood and dissolving stasis TCM intersection network, and 180 positive nodes and 42 negative nodes were obtained. In this article, 9 positive nodes, including calnexin, interleukin-1, tumor necrosis factor, were taken as examples to analyze the action mechanism of TCM for preventing and treating CHD. The results showed that the network potential key target analysis method was helpful to explore the potential action targets of activating blood and dissolving stasis TCMs for preventing and treating CHD, methodologically supportive to reveal the action mechanism of TCMs at molecular and systematic levels, and significant in guiding the research and development of new drugs.

Half of the 2015 Nobel Prize in Physiology or Medicine was awarded to Chinese scientist Youyou Tu in recognition of her pioneering work on the antimalarial artemisinin, extracted from Artemisia annua, a traditional Chinese herbal remedy used to treat fever. This is clearly a great encouragement for scientists who engage traditional medicine research. As Youyou Tu stated in her Nobel Prize awarding lecture, artemisinin is a gift from traditional Chinese medicine (TCM) to the world, this definitely will generate great interest in not only TCM but also other traditional medicine systems from other parts of the world, including Europe, Africa, India, Americas, etc. Though the Nobel Prize selection committee did not confess that the prize is to award traditional Chinese medicine, rather a new drug discovery inspired from TCM, this is indeed the exciting and encouraging event for Chinese TCM scientists. In my opinion, it is meaningless to dispute if artemisinin is still belonging to TCMor westernmedicine. Any contribution or new discovery derived from TCM to benefit for the human health should be recognized and respected. TCM needs to be developed and modernized. Any standpoint that developed or modernized TCM does not belong to TCM may drastically hinder the TCM modernization and integration with modern medicine process, or even deepen the gap between TCM and modern medicine. Evidence-based medicine is the future of TCM by means of modern biomedicine advances and novel approaches. In the past 20 years, TCM has undergone rapid development period evidenced by a number of achievements including the geometric growth of TCM research papers, booming TCM industry, TCM new drug research and development, etc. However, TCM is still facing grand challenges in the future development. Shortage of modern scientific evidence for safety, effectiveness, quality and mode of action should be emphasized and dealt with solutions. TCM experienced-based feature should be turned into evidence-based and science-based one. Following several aspects are suggested for the future modern TCM research: a) TCM-based new drug discovery. TCM is still a non-fully explored treasure house for new drug discovery and development. According to TCM resource survey, there are over 12000 TCM species, among which majority are herbs. Apart from artemisinin and its derivatives, a number of single chemical entity drugs have been developed and successfully marketed, such as arsenic trioxide, ginsenoside Rg3, bifendate, β-elemene, indirubin, etc. It is anticipated that more new drugs could be discovered from this vast TCM resource with modern drug discovery technology and methodology. b) Research on the holistic TCM quality control. The current quality control approach is more focused on a single marker or a few marker determinations, which follows the western drug quality control model and hence, could not really monitor the quality of TCM products. Systemic and comprehensive quality control method should be developed for the TCM crude drugs, prepared slices and finished products, especially for those multiple-ingredient herbal products. c) Research on TCM processing. All TCM crude drugs should be processed in different extent before they can be used either for decoction or for herbal production. TCM processing method is mainly based on the traditional knowledge or experience. Mechanism of processing either for the purpose of enhancing efficacy or eliminating toxicity should be thoroughly investigated and clarified. d) TCM efficacy and safety research. During the development of TCM, greater attention needs to be paid to the integrated evaluation of the effectiveness and safety based on TCM theory and modern scientific research. New evaluation methodology fit for TCM complex feature should be developed with international collaborations. Globally recognized evaluation criteria should be constructed. Other TCM research focuses include pharmacokinetics, geo-authenticity, active principles and giant data library. It is firmly believed that TCM will contribute more than ever to the human health along with the rapid advances of biomedicine science and eventually developed into an evidence-based medicine system.

Traditional Chinese Medicine (TCM) documented about 100,000 formulae during past 2500 years. To use and customize them by modern pharmaceutical industry, we make an interdisciplinary effort to study the activity of new drug research and development (R&D) in TCM by introducing data mining approaches to it. We used the migraine formulae as a training set to investigate the possibility of developing new prescription by means of data mining. The activity of new drug R&D of TCM consists of two steps. The first step is to discover new prescriptions (candidates for drugs) from migraine formulae. We present an unsupervised clustering approach based on data mining theory to address the problem in the first step and automatically discover ten new prescriptions from the formulae data. The second step is to develop and optimize the prescriptions discovered by current biomedical approaches. Since Ligusticum chuanxiong Hort (LCH), a kind of herb, is often used to treat migraine and appears in the new prescriptions, we use it as an example and apply supervised regression method based on data mining theory to study the drug R&D activity of TCM. We revised two linear regression methods in order to establish the nonlinear association between three chemical ingredients of LCH and corresponding pharmacological activity and used it to predict the activities. The association is validated by in vitro experiments and we found that the experimental results are consistent with the prediction. Unsupervised clustering and supervised regression cover most part of data mining theory, which means that data mining approaches play a crucial role in new drug R&D in TCM and present a better solution to establish the platform of drug R&D in TCM.