Exploring the molecular mechanisms of Traditional Chinese Medicine components using gene expression signatures and connectivity map

Amid the establishment and optimization of Connectivity Map (CMAP), the functional relationships among drugs, genes, and diseases are further explored. This biological database has been widely used to identify drugs with common mechanisms, repurpose existing drugs, discover the molecular mechanisms of unknown drugs, and find potential drugs for some diseases. Research on traditional Chinese medicine (TCM) has entered a new era in the wake of the development of bioinformatics and other subjects including network pharmacology, proteomics, metabolomics, herbgenomics, and so on. TCM gradually conforms to modern science, but there is still a torrent of limitations. In recent years, CMAP has shown its distinct advantages in the study of the components of TCM and the synergetic mechanism of TCM formulas; hence, the combination of them is inevitable.

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The Integrated RNA Landscape of Renal Preconditioning against Ischemia-Reperfusion Injury

Journal of the American Society of Nephrology ◽

10.1681/asn.2019050534 ◽

2020 ◽

Vol 31 (4) ◽

pp. 716-730 ◽

Cited By ~ 1

Author(s):

Marc Johnsen ◽

Torsten Kubacki ◽

Assa Yeroslaviz ◽

Martin Richard Späth ◽

Jannis Mörsdorf ◽

...

Keyword(s):

Gene Expression ◽

Reperfusion Injury ◽

Caloric Restriction ◽

Molecular Mechanisms ◽

Target Genes ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Hypoxic Preconditioning ◽

Preventive Strategies ◽

Gene Expression Signatures

BackgroundAlthough AKI lacks effective therapeutic approaches, preventive strategies using preconditioning protocols, including caloric restriction and hypoxic preconditioning, have been shown to prevent injury in animal models. A better understanding of the molecular mechanisms that underlie the enhanced resistance to AKI conferred by such approaches is needed to facilitate clinical use. We hypothesized that these preconditioning strategies use similar pathways to augment cellular stress resistance.MethodsTo identify genes and pathways shared by caloric restriction and hypoxic preconditioning, we used RNA-sequencing transcriptome profiling to compare the transcriptional response with both modes of preconditioning in mice before and after renal ischemia-reperfusion injury.ResultsThe gene expression signatures induced by both preconditioning strategies involve distinct common genes and pathways that overlap significantly with the transcriptional changes observed after ischemia-reperfusion injury. These changes primarily affect oxidation-reduction processes and have a major effect on mitochondrial processes. We found that 16 of the genes differentially regulated by both modes of preconditioning were strongly correlated with clinical outcome; most of these genes had not previously been directly linked to AKI.ConclusionsThis comparative analysis of the gene expression signatures in preconditioning strategies shows overlapping patterns in caloric restriction and hypoxic preconditioning, pointing toward common molecular mechanisms. Our analysis identified a limited set of target genes not previously known to be associated with AKI; further study of their potential to provide the basis for novel preventive strategies is warranted. To allow for optimal interactive usability of the data by the kidney research community, we provide an online interface for user-defined interrogation of the gene expression datasets (http://shiny.cecad.uni-koeln.de:3838/IRaP/).

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The Chinese Medicinal Formulation Guzhi Zengsheng Zhitongwan Modulates Chondrocyte Structure, Dynamics, and Metabolism by Controlling Multiple Functional Proteins

BioMed Research International ◽

10.1155/2018/9847286 ◽

2018 ◽

Vol 2018 ◽

pp. 1-12

Author(s):

Baojin Yao ◽

Bocheng Lu ◽

Mei Zhang ◽

Hongwei Gao ◽

Xiangyang Leng ◽

...

Keyword(s):

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Research Field ◽

Medical Systems ◽

Cellular Processes ◽

Structure Dynamics ◽

National Medical ◽

Medicinal Formulation

Traditional Chinese medicine is one of the oldest medical systems in the world and has its unique principles and theories in the prevention and treatment of human diseases, which are achieved through the interactions of different types of materia medica in the form of Chinese medicinal formulations. GZZSZTW, a classical and effective Chinese medicinal formulation, was designed and created by professor Bailing Liu who is the only national medical master professor in the clinical research field of traditional Chinese medicine and skeletal diseases. GZZSZTW has been widely used in clinical settings for several decades for the treatment of joint diseases. However, the underlying molecular mechanisms are still largely unknown. In the present study, we performed quantitative proteomic analysis to investigate the effects of GZZSZTW on mouse primary chondrocytes using state-of-the-art iTRAQ technology. We demonstrated that the Chinese medicinal formulation GZZSZTW modulates chondrocyte structure, dynamics, and metabolism by controlling multiple functional proteins that are involved in the cellular processes of DNA replication and transcription, protein synthesis and degradation, cytoskeleton dynamics, and signal transduction. Thus, this study has expanded the current knowledge of the molecular mechanism of GZZSZTW treatment on chondrocytes. It has also shed new light on possible strategies to further prevent and treat cartilage-related diseases using traditional Chinese medicinal formulations.

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The impact of Traditional Chinese Medicine on mitophagy in disease models

Current Pharmaceutical Design ◽

10.2174/1381612827666211006150410 ◽

2021 ◽

Vol 27 ◽

Author(s):

Li-Ping Yu ◽

Ting-Ting Shi ◽

Yan-Qin Li ◽

Jian-Kang Mu ◽

Ya-Qin Yang ◽

...

Keyword(s):

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Molecular Mechanisms ◽

Human Diseases ◽

Regulatory Mechanisms ◽

Disease Models ◽

Relationship Of ◽

The Impact ◽

The Relationship

: Mitophagy plays an important role in maintaining mitochondrial quality and cell homeostasis through the degradation of damaged, aged, and dysfunctional mitochondria and misfolded proteins. Many human diseases, particularly neurodegenerative diseases, are related to disorders of mitochondrial phagocytosis. Exploring the regulatory mechanisms of mitophagy is of great significance for revealing the molecular mechanisms underlying the related diseases. Herein, we summarize the major mechanisms of mitophagy, the relationship of mitophagy with human diseases, and the role of traditional Chinese medicine (TCM) in mitophagy. These discussions enhance our knowledge of mitophagy and its potential therapeutic targets using TCM.

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Potential Natural Compounds for the Prevention and Treatment of Nonalcoholic Fatty Liver Disease: A Review on Molecular Mechanisms

Current Molecular Pharmacology ◽

10.2174/1874467215666211217120448 ◽

2021 ◽

Vol 15 ◽

Author(s):

Cheng Ma ◽

Cheng Wang ◽

Yafang Zhang ◽

Honglin Zhou ◽

Yunxia Li

Keyword(s):

Liver Disease ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Fatty Liver Disease ◽

Molecular Mechanisms ◽

Natural Compounds ◽

Nonalcoholic Fatty Liver ◽

Prevention And Treatment

Background: Nonalcoholic fatty liver disease (NAFLD) is a kind of metabolic stress-induced liver injury closely related to insulin resistance and genetic susceptibility, and there is no specific drug for its clinical treatment currently. In recent years, a large amount of literature has reported that many natural compounds extracted from traditional Chinese medicine (TCM) can improve NAFLD through various mechanisms. According to the latest reports, some emerging natural compounds have shown great potential to improve NAFLD but are seldom used clinically due to the lacking special research. Purpose: This paper aims to summarize the molecular mechanisms of the potential natural compounds on improving NAFLD, thus providing a direction and basis for further research on the pathogenesis of NAFLD and the development of effective drugs for the prevention and treatment of NAFLD. Methods: By searching various online databases, such as Web of Science, SciFinder, PubMed, and CNKI, NAFLD and these natural compounds were used as the keywords for detailed literature retrieval. Results: The pathogenesis of NAFLD and the molecular mechanisms of the potential natural compounds on improving NAFLD have been reviewed. Conclusion: Many natural compounds from traditional Chinese medicine have a good prospect in the treatment of NAFLD, which can serve as a direction for the development of anti-NAFLD drugs in the future.

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Effect and Molecular Mechanisms of Traditional Chinese Medicine on Tumor Targeting Tumor-Associated Macrophages

Drug Design Development and Therapy ◽

10.2147/dddt.s223646 ◽

2020 ◽

Vol Volume 14 ◽

pp. 907-919 ◽

Cited By ~ 1

Author(s):

Jing He ◽

Peihao Yin ◽

Ke Xu

Keyword(s):

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Tumor Targeting ◽

Molecular Mechanisms ◽

Tumor Associated Macrophages

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Effects of Huangqi (Hex) on Inducing Cell Differentiation and Cell Death in K562 and HEL Cells¤

Acta Biochimica et Biophysica Sinica ◽

10.1093/abbs/36.3.211 ◽

2004 ◽

Vol 36 (3) ◽

pp. 211-217 ◽

Cited By ~ 25

Author(s):

Xiao-Dong Cheng ◽

Chun-Hui Hou ◽

Xue-Jun Zhang ◽

Heng-Yue Xie ◽

Wei-Ying Zhou ◽

...

Keyword(s):

Cell Death ◽

Chinese Medicine ◽

Side Effects ◽

Traditional Chinese Medicine ◽

Molecular Mechanisms ◽

Caspase 3 ◽

Globin Gene ◽

Terminal Differentiation ◽

Point Of View ◽

Hel Cells

Abstract Huangqi (Astragalus membranaceus), a traditional Chinese medicine, has been used to ameliorate side effects of cancer chemotherapy in China. However, little is known about its molecular mechanisms. Here we show that induction of K562 or HEL cells with 1.5 mg/ml of Huangqi (Hex) (Components extracted from Huangqi) for 3–5 d results in the expression of β-globin gene in both cell lines and leads to terminal differentiation. Moreover, the apoptosis in HEL cells can be induced by increasing concentration of Huangqi (Hex) to 4.5 mg/ml for 3–5 d. Upregulation of Apaf-1, caspase-3 and acetylcholinesterase (AChE) in HEL cells may play a crucial role in the process of apoptosis. The prospect of inducing expression of adult (β) globin gene and apoptosis selectively in cancer cells is obviously attractive from a therapeutic point of view.

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Advancing Drug Discovery and Development from Active Constituents of Yinchenhao Tang, a Famous Traditional Chinese Medicine Formula

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/257909 ◽

2013 ◽

Vol 2013 ◽

pp. 1-6 ◽

Cited By ~ 41

Author(s):

Aihua Zhang ◽

Hui Sun ◽

Shi Qiu ◽

Xijun Wang

Keyword(s):

Systems Biology ◽

Drug Discovery ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Molecular Mechanisms ◽

Synergistic Effects ◽

Molecular Networks ◽

Agile Development ◽

Therapeutic Effects ◽

Systematic Analysis

Traditional Chinese medicine (TCM) formula has been playing a very important role in health protection and disease control for thousands of years. Guided by TCM syndrome theories, formula are designed to contain a combination of various kinds of crude drugs that, when combined, will achieve synergistic efficacy. However, the precise mechanism of synergistic action remains poorly understood. One example is a famous TCM formula Yinchenhao Tang (YCHT), whose efficacy in treating hepatic injury (HI) and Jaundice syndrome, has recently been well established as a case study. We also conducted a systematic analysis of synergistic effects of the principal compound using biochemistry, pharmacokinetics and systems biology, to explore the key molecular mechanisms. We had found that the three component (6,7-dimethylesculetin (D), geniposide (G), and rhein (R)) combination exerts a more robust synergistic effect than any one or two of the three individual compounds by hitting multiple targets. They can regulate molecular networks through activating both intrinsic and extrinsic pathways to synergistically cause intensified therapeutic effects. This paper provides an overview of the recent and potential developments of chemical fingerprinting coupled with systems biology advancing drug discovery towards more agile development of targeted combination therapies for the YCHT.

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A Network Pharmacology-Based Study on the Anti-Lung Cancer Effect of Dipsaci Radix

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/7424061 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Jiayan Wu ◽

Shengkun Hong ◽

Xiankuan Xie ◽

Wangmi Liu

Keyword(s):

Lung Cancer ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Molecular Mechanisms ◽

Target Genes ◽

Interaction Network ◽

Network Pharmacology ◽

Pathway Enrichment Analysis ◽

Hub Genes ◽

Active Compounds

Objective. Dipsaci Radix (DR) has been used to treat fracture and osteoporosis. Recent reports have shown that myeloid cells from bone marrow can promote the proliferation of lung cancer. However, the action and mechanism of DR has not been well defined in lung cancer. The aim of the present study was to define molecular mechanisms of DR as a potential therapeutic approach to treat lung cancer. Methods. Active compounds of DR with oral bioavailability ≥30% and drug-likeness index ≥0.18 were obtained from the traditional Chinese medicine systems pharmacology database and analysis platform. The potential target genes of the active compounds and bone were identified by PharmMapper and GeneCards, respectively. The compound-target network and protein-protein interaction network were built by Cytoscape software and Search Tool for the Retrieval of Interacting Genes webserver, respectively. GO analysis and pathway enrichment analysis were performed using R software. Results. Our study demonstrated that DR had 6 active compounds, including gentisin, sitosterol, Sylvestroside III, 3,5-Di-O-caffeoylquinic acid, cauloside A, and japonine. There were 254 target genes related to these active compounds as well as to bone. SRC, AKT1, and GRB2 were the top 3 hub genes. Metabolisms and signaling pathways associated with these hub genes were significantly enriched. Conclusions. This study indicated that DR could exhibit the anti-lung cancer effect by affecting multiple targets and multiple pathways. It reflects the traditional Chinese medicine characterized by multicomponents and multitargets. DR could be considered as a candidate for clinical anticancer therapy by regulating bone physiological functions.

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