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A Peer-reviewed, open access journal sponsored by TMR publishing group
Editor-in-Chief: Dan Chen, PhD. Prof.
ISSN 2624-3075
7Drug Combination Therapy (DCT, ISSN: 2624-3075) is a Peer-reviewed, Open Access, Academic, quality international journal sponsored by TMR publishing group. DCT aims to publish unbiased original articles, reviews and letters in all areas of drug combination therapy. It has been included in ScienceOpen, Google Scholar, VIP Data, CNKI, Superstar Journals Database and Traditional Medicine Research Data Expanded. DCT is dedicated to report the latest advancements and the research done in drug combination along with all the relevant fields, including but not limited to prescription compatibility studies, disassembled studies, drug compatibility synergetic/antergic mechanisms, combination therapy for specific populations, integrated pharmacology studies, system/network pharmacology, big data analysis, systematic evaluation/meta-analysis, omics research, etc. In this context, studying the effects of a combination of drugs in order to provide evidence of a significant superiority compared to the single agents is of particular interest. ... More

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Current Issue     09 August 2019, Volume 1 Issue 3 Previous Issue   
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Editor-in-Chief of Special Issue on Network Pharmacology
7Drug Combination Therapy. 2019, 1 (3)  
Abstract ( 40 )     PDF (134KB) ( 19 )  

Dr. Yong-Hua Wang is working as a Professor and Doctoral supervisor in Northwest University, China. Dr. Wang also serves as the vice president of the National Medicine Information and Big Data Branch, the director of Network Pharmacology Society, etc.

 

Dr. Wang focuses on the research of systems pharmacology and technology application in the past decades. He has published 110 SCI papers. Among them, 49 SCI papers (in the past five years) were published in Science (special issue of ethnomedicine), Brief Bioinform, Bioinformatics, ACS Chem Bio, etc., including one ESI “Highly Cited Paper”. And the citation of the papers has reached 4100 times (H-index 35). Besides, the unique TCM systems pharmacology platform developed by Dr. Wang, called TCMSP (http://lsp.nwu.edu.cn/tcmsp.php), has been used by scientific research institutions in 83 countries and regions. In the past four years, the paper of TCMSP has been cited more than 700 times. Furthermore, by integrating the rich research experiences over the past decades of himself, Dr. Wang wrote a monograph: “Systematic Pharmacology”.

 

So far, Dr. Wang has won the second prize of Shaanxi Science and Technology Progress Award, China (No.1), Shaanxi Youth Science and Technology Award, China (No.1), and the second prize of National Science and Technology Progress Award, China (No.5). And Dr. Wang was also been selected as a special professor of the “Thousand Talents Program” of Shaanxi Province of China and a new century talent of the Ministry of Education of the People’s Republic of China. Until now, Dr. Wang presides over four projects of the National Natural Science Foundation of China.

Orginal Article
Research trends and development status of TCM network pharmacology: a bibliometric study
Yu-Zhi Shang, Qing-Huai Zhang, Qiu-Xia Chen, Xiu-Song Tang, Yu-Zhou Pang, Gang Fang
7Drug Combination Therapy. 2019, 1 (3): 102-116.   https://doi.org/10.12032/DCT201903002
Abstract ( 111 )     PDF (818KB) ( 39 )  

Objective: To analyze the research status, development context and trend of traditional Chinese medicine (TCM) network pharmacology from birth to the present. Methods: In this study, bibliographic data and references of articles on TCM network pharmacology were collected from Web of Science Core Collection (WoSCC), and software including CiteSpace, VOSviewer and Microsoft Excel were applied for the bibliometric analysis of periodicals and the quantity of literature, and for the construction and analysis of the co-occurrence network of countries, journals, research institutes and authors, clusters of co-cited references, and time distribution network of keywords. Results: 249 articles were included in this study. The time span was from 2011 to 2018, and the annual volume of publications showed an increasing trend year by year. The 77 journals contain relevant literature, and the average impact factor of the journal is 3.215. Chinese Journal of Natural Medicines, Scientific Reports, PLoS One have high influence in the field of TCM network pharmacology. Universities and research institutes including China Academy of Chinese Medical Science and Northwest Agriculture & Forestry University are the major forces in this field. Wang Yonghua and Li Shao are authors with high influence in this field, with a considerable number of relevant documents and citations. According to the clustering results of co-cited references, research topics can be classified into 13 development contexts such as “compound danshen formula”, “computational tool”, and “new multi-compound drug discovery”. Hotspots of TCM network pharmacology include “drug discovery”, “mechanism” and “cardiovascular disease”, and relevant research methods and research contents including drugs and diseases tend to be constantly enriched. Conclusion: This study comprehensively demonstrates the research status, development context and trends of TCM network pharmacology, and provides a scientific reference for TCM network pharmacology researchers.

Dissecting the underlying pharmaceutical mechanism of traditional Chinese medicine Wenxin Keli acting on atrial fibrillation through network pharmacology
Xian-Jun Wu, Xin-Bin Zhou, Chen Chen, Wei Mao
7Drug Combination Therapy. 2019, 1 (3): 117-133.   https://doi.org/10.12032/DCT201903003
Abstract ( 108 )     PDF (1072KB) ( 76 )  

As a well-known Chinese medicine prescription, Wenxin Keli (WXKL) has been widely used in the treatment of many arrhythmias including atrial fibrillation and has achieved significant clinical effects, but the specific mechanism of its treatment of atrial fibrillation remains unclear. This study used a network pharmacology approach to reveal the potential molecular mechanisms of WXKL in the treatment of atrial fibrillation. It involves oral bioavailability screening of ingredients, drug-likeness evaluation, compound target fishing, H-C-T network and C-T-P network construction and analysis. Through the network pharmacology-based research strategy, the complex system of WXKL was analyzed. It was found that 14 representative compounds of WXKL, 30 protein targets and 12 related signaling pathways help us systematically understand the underlying mechanism of WXKL's anti-atrial fibrillation effects.

A network pharmacological study on the potential mechanism of Yinchenhao Decoction in treatment of chronic hepatitis B
Jin-Yu Zhang, Xian-Fa Cai
7Drug Combination Therapy. 2019, 1 (3): 134-152.   https://doi.org/10.12032/DCT201904002
Abstract ( 115 )     PDF (1206KB) ( 49 )  

Background: Yinchenhao Decoction (YCHD), an ancient Chinese herbal medicinal compound prescribe for the treatment of jaundice, which long-term clinical experience and randomized trials have shown was effective against chronic hepatitis B (CHB). However, its mechanism remained unknown. With the gradual separation of pharmacodynamic components in YCHD and the development of computer virtual technology, network pharmacology provides an opportunity. Our study is to explore the underlying mechanism of YCHD for the treatment of CHB. Methods: The active compounds of YCHD were screened from TCMSP database, whose targets were predicted based on the ligands structures and the targets of CHB was selected from the TTD, DisGeNET, and Drugbank databases to obtain the potential targets of YCHD for CHB treating. Cytoscape 3.6.1 was applied for network analysis to identify key targets, and gene enrichment of the targets shared by both YCHD and CHB was performed by DAVID database. The virtual verification of binding activities between the target protein and the small molecule was finally performed by the Sytems Dock platform. Results: The potentially important targets associated with CHB corresponding to 33 compound components from YCHD included ESR1, CYP1A2, PTGS2, CYP1A1, ABCG2, MMP9. Besides, enriched were the related 8 KEGG pathways (P<0.05) such as ABC transporters, Bile secretion, TNF signaling pathway. Conclusions: This study used network pharmacology method to reveal the characteristics, “multi-component and multi-target and multi-pathway”, of YCHD on CHB treatment, providing thoughts for further research.

Curcumin suppresses proliferation of MCF-7 breast cancer cells by modulating gap junction signaling
Xin-Qiang Song, Mu Zhang, Kai-Ming Li, Er-Qin Dai, Yu Zhang, Ning-Ning Yang, Lei Chen, Lei Wang
7Drug Combination Therapy. 2019, 1 (3): 153-164.   https://doi.org/10.12032/DCT201904001
Abstract ( 52 )     PDF (949KB) ( 22 )  

Curcumin, an agent isolated from turmeric, shows therapeutic potential against breast cancer. However, the mechanism underlying anticancer activity has not been fully expounded. In this research, bioinformatics was utilized to analyze molecular mechanism of curcumin. and the results have been proved in breast cancer cells subsequently. In order to generate a breast cancer molecular network with which curcumin interacts, target proteins of curcumin from PubChem were combined with genes implicated in breast cancer in the NCBI within Ingenuity Pathway Analysis software.Predicted curcumin targets were verified by reverse transcription-quantitative polymerase chain reaction. Bioinformatics identified gap junction signaling and 14-3-3-mediated adherens junctions as the main canonical signaling pathways targeted by curcumin. Moreover, curcumin can substantially up-regulates the gap junction protein connexin in breast cancer cells. Our results suggest that curcumin through modulation of the gap junction signaling pathway to inhibit cell proliferation and differentiation in breast cancer cells.

Mini-Review
A clue to potential therapeutic targets: application of integrative medicine and bioinformatics
Shi-Lin Xia, Han Liu, Shinobu Mizushima, Akio Mizushima
7Drug Combination Therapy. 2019, 1 (3): 165-172.   https://doi.org/10.12032/DCT201903004
Abstract ( 68 )     PDF (912KB) ( 15 )  

More and more evidence show that the targets of traditional Chinese medicine are a resource pool that contributes to the modern medicine. A key aspect of medicine research is to address the issue how to look for a clue of potential therapeutic molecular targets by interdisciplinary approaches. With the development of high throughput technology, a considerable amount of data has been emerging. The application of these big data is not so efficient as the generation of them. This paper attempts to show that interdisciplinary analysis contributes to the discovery of targets at the initial stage of drug research, indicating that it is necessary to explore the drug research and development with interdisciplinary approaches between integrative medicine and bioinformatics.

Data Mining
Analysis on the medication rules and mechanisms of action of traditional Chinese medicine in treating cervical cancer
Ying Chen, Yao Yang, Xin-Zhe Zhao, Guo-Wei Zhang
7Drug Combination Therapy. 2019, 1 (3): 173-185.   https://doi.org/10.12032/DCT201903001
Abstract ( 75 )     PDF (1163KB) ( 48 )  

Objective: To summarize the rule of application of traditional Chinese medicine (TCM) in the prevention and treatment of cervical cancer, and to explore the molecular mechanism of the compatibility of core herbs. Methods: Collect relevant literatures on cervical cancer in Chinese National Knowledgey Ifrastructure (CNKI), use TCM inheritance platform system (TCMISSV2.5) for association rules and complex system entropy clustering analysis; use BATMAN-TCM online analysis tools to construct target-pathway-disease network to reveal the underlying mechanisms of action. Results: Among the 78 prescriptions selected, a total of 172 Chinese medicines were used, and the five most frequently used herbs were Huang-bo (Phellodendri Chinrnsis Cortex), Fu-ling (Poria Cocos), Huang-qi (Hedysarum Multijugum Maxim.), Bai-hua-she-she-cao (Hedyotis Diffusae
Herba
) and Gan-cao (Licorice). Bai-hua-she-she-cao (Hedyotis Diffusae Herba) and Huang-qi (Hedysarum Multijugum Maxim.), Bai-hua-she-she-cao (Hedyotis Diffusae Herba) and Fu-ling (Poria Cocos), Bai-zhu (Atractylodes Macrocephala Koidz.) and Fu-ling (Poria Cocos) are the three most commonly used medicine match. In addition, through cluster analysis, a total of 4 core herbs ompatibility and 2 new prescriptions were excavated. Herbs in the new prescriptions which are used to clearing heat-toxin and removing dampness were most frequently used. Through the analysis of
the signal pathway of high frequency Chinese medicines, we found that neuroactive ligand-receptor interaction pathway may play important roles.
Conclusion: The core Chinese medicines for the prevention and treatment of cervical cancer are mainly clearing heat-toxin and removing dampness.
The core Chinese medicines may play their anti-cervical cancer by interfering with the neuroactive ligand-receptor interaction signaling pathway.

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  • Systematic evaluation and meta-anlysis of the efficacy of Xiaochaihu Decoction in the treatment of chronic superficial gastritis 
    ...

    Objective: To compare the effectiveness of Xiaochaihu Decoction (XCHD) or the modified XCHD combined with western medicine in the treatment of superficial gastritis. Methods: We collected the studies about XCHD or the modified XCHD combined with western medicine for superficial gastritis in China Biology Medicine (CBM) Database (2010-2018), China National Knowledge Infrastructure (CNKI) Database (2010-2018), VIP Database (2010-2018), Wanfang Database (2010-2018) and the Back Issues Database of Hebei University. The randomized controlled trials (RCTs) were included in this study. The literatures were independently extracted by two researchers and the Cochrane Review Handbook (version 5.1.0) was applied to assess the quality of included trials. Statistical analysis was performed with RevMan (version 5.3). Results: A total of 8 RCTs, including 732 cases, were included finally. Meta-analysis results showed that compared with the western medicine treatment group, XCHD or the modified XCHD combined with western medicine could improve the total effective rate [OR=4.67, 95%CI (2.90,7.55), P<0.00001], physiological function [MD=10, 95%CI (8.78,11.23), P<0.00001], role physical [MD=13.85, 95%CI (11.19,16.51), P<0.00001], physical pain [MD=11.64, 95%CI (9.05,14.23), P<0.00001], general health [MD=11.20, 95%CI (9.52,12.88), P<0.00001], vitality [MD=13.46, 95%CI (12.30,14.62), P<0.00001], social function [MD=19.20, 95%CI (17.32,21.09), P<0.00001], affection  function [MD=30.3, 95%CI (28.99,31.62), P<0.00001], mental health [MD=9.80, 95%CI (8.44,11.16), P<0.00001]. Conclusion: XCHD or the modified XCHD combined with western medicine in the treatment of superficial gastritis has good performance in clinical efficacy and the improvement of quality of life. However, with several methodology problems existing in the included RCTs, the effectiveness of XCHD or the modified XCHD is still need more high-quality randomized, double-blind, placebo-controlled trials to further confirmed.

    ...
    Shi-Jun Li, Teng Huang, Xiao-Li Ma
  • Systematic pharmacology analysis of Sodium 8-(((carboxymethyl)amino)methyl)-4’,7-bishydroxy-isoflavone-3’-sulfonate 
    ...

    The purpose of this study is to use the newly synthesized molecule M as a research object, the pharmacological mechanism of the molecule was analyzed by using a series of Systematic pharmacology methods. The results show that the M molecule has a higher drug-like DL value of 0.59 and better molecular property parameters, namely Hdon=4, Hacc=10 and AlogP=0.94;A total of 11 M molecules related targets, namely F2, ESR1, AR, F10, CA2, DPP4, CCNA2, PRSS1, CDK2, GSK3B and PTPN1; A total of 140 diseases are associated with M molecule targets, and these diseases are mainly related to cancer and cardiovascular diseases; A total of 52 pathways involve the pharmacological mechanisms of M molecules, which are mainly related to cancer and other related diseases; GO-enriched analysis showed that these targets are closely related to the regulation of peptidase activity and biological processes such as blood coagulation and hemostasis. This article clearly demonstrated the pharmacological mechanism of M molecule, which provides references for exploring the pharmacological mechanism of new compounds.

    ...
    Ze-Ping Luo, Li-Wei Pan, Hai-Lin Chen, Jun-Yu Lu
  • Research progress of Yinchenhao Decoction in the treatment of non-alcoholic fatty liver disease 
    ...
    Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. Non-alcoholic steatohepatitis (NASH) is the most serious type and a turning point in the progression of NAFLD. If not treated actively, NASH will progress to irreversible liver damage such as cirrhosis and hepatocellular carcinoma. At present, there are no specific therapeutic drugs in western medicine. The treatment methods are mainly to improve lifestyle and exercise therapy, to alleviate the symptoms of discomfort, delay the progress of the disease, and improve the quality of life. However, the effect is often not ideal, prone to recurrence, and compliance is relatively poor. Dramatically, traditional Chinese medicine has certain advantages in the treatment of NAFLD. Modern research has confirmed that Yinchenhao Decoction has a good effect on liver-protective and choleretic action and improving liver function. It has significant curative effect on various liver and gallbladder diseases such as acute liver injury and alcoholic liver disease. This article summarized the clinical and basic research of Yinchenhao Decoction in the treatment of NAFLD. We found that Yinchenhao Decoction can enhance the efficiency of NAFLD and improve symptoms such as dizziness, liver pain, hepatosplenomegaly and indigestion. The mechanisms may be related to that Yinchenhao decoction improves the disorder of glucose and lipid metabolism, inflammatory state and liver function.
    ...
    Xiao-Ting Ma, Jing-Na Zhou, Shou-Jing Sheng, Shao-Qin Ge
  • Analysis of prescription rules in the treatment of diabetic heart disease based on traditional Chinese medicine inheritance support system 
    ...
    Diabetes is a common clinical disease and has many complications, among which diabetic heart disease is the leading cause of death in diabetic patients. This article collected the prescriptions for the treatment of diabetic heart disease, and used the traditional Chinese medicine inheritance support system to explore the prescription formulation rules. Finally, we included 43 prescriptions for analysis. We found that the rules of formulas for treating diabetic heart disease are complex, but Chinese medicines in these formulas are mainly with the effects of nourishing Qi, nourishing Yin and activating blood circulation. At the same time, we obtained 3 new prescriptions and discussed the clinical rationality of the new prescriptions. The purpose of this article is to provide reference for clinical prescription in the treatment of diabetic heart disease and the development of related new drugs.
    ...
    Jing-Na Zhou, Xiao-Ting Ma, Guo-Wei Zhang