Deciphering potential pharmacological mechanisms of Danhong injection to treat chronic stable angina based on drug response-related modules and genes.

ETHNOPHARMACOLOGICAL RELEVANCE: Danhong injection (DHI), a traditional Chinese medicine (TCM) injection that has been widely used to treat coronary heart disease and angina pectoris. However, its underlying pharmacological mechanisms have not been fully elucidated. Not all patients benefit from DHI to the same extent. We attempted to explore the characteristics of potential therapeutic targets in different responsive populations. AIM OF THE STUDY: This study aimed to reveal the potential molecular mechanisms of DHI in treating chronic stable angina and identify potential therapeutic targets for DHI. MATERIALS AND METHODS: Based on a previous phase IV clinical trial of DHI in treating chronic stable angina, drug response modules were identified through structural entropy and similarity. Drug response-related genes were screened out based on the correlations between drug response module/module-related genes and clinical features and were assessed using a random forest model. Further validation was conducted using a hypoxia/reoxygenation (H/R) model. RESULTS: Seven DHI-related response modules were identified. Eight drug response-related genes were screened out, and principal component analysis showed that DHI responders were distinguished from responders in the control group based on their expression values. The combination of the two most important genes, SHC4 and PIP5K1P1, discriminated between responders and nonresponders with an area under the receiver operating characteristic curve (AUC) of 0.714; however, no significant difference was found in the AUC between the combination and a single gene. Reverse transcription-polymerase chain reaction showed that middle-dose DHI treatment significantly decreased SHC4 mRNA expression compared with that in the H/R group (P = 0.026), a finding consistent with our previous analysis of differentially expressed genes. CONCLUSIONS: DHI comprehensively exerted a therapeutic effect by acting on multiple response modules related to angina pectoris and drug response-related genes. Our findings indicate that the dimensionality reduction strategy based on the target network-drug response module-therapeutic targets can contribute to revealing the mechanism of action of TCM compounds and guiding precise clinical medication.

Pluripotent anti-inflammatory immunomodulatory effects of papaverine against cerebral ischemic-reperfusion injury.

The mechanism of the papaverine (PV) for the treatment of cerebral ischemia remains unclear. A total of 42 mice induced with focal cerebral ischemia were randomly divided into three groups: PV,baicalin (BA)and vehicle group. Both PV and BA could significantly reduce the ischemic infarct volume (P < 0.05). Pathway enrichment analysis was performed on MetaCore™ to search the molecular pathways associated with the gene expression profile of PV, compared with vehicle and BA. Compared with vehicle, we found that 60% of the top 10 pathways in PV group were related to immune response. The top 10 biological processes of the targeted pathways were mainly related to the multiple immunomodulatory process of neuro-vascular inflammation, including immune_Th17-deried cytokins, regulation of angiogenesis, cell adhesion_Leucocyte chemotaxis, antigen presentation, cell adhesion_synaptic contact, and inflammation related to Amphoterin signaling. Moreover, compared with BA, 17 pathways of PV were identified, and 58.82% (10/17) were also related to immune response, especially, half of the top 10 pathways with the lower p-value. In these top 10 pathways, 4 were the cytokine-mediated signaling pathways, which play key role in inflammation, like IL-17 signaling pathways with the activation of G-CSF,IL-23,RANKL, p38MAPK and NF-κB.These findings indicate that PV may be an efficacious pluripotent anti-inflammatory agent against cerebral ischemic-reperfusion injury by targeting on multiple immunomodulatory process of neuro-vascular inflammation.

[Multi-dimensional mining and analysis of core prescriptions in launched Chinese patent medicine for treatment of influenza].

Through the multi-dimensional mining and analysis of launched anti-influenza proprietary Chinese medicines,this paper explores the study of the prescriptions and pharmacodynamics of traditional Chinese medicines for influenza. We established a standardized database by collecting and excavating the launched Chinese patent medicines that clearly describe the treatment of influenza. Frequency analysis and association rules were used to analyze the frequency of Chinese patent medicines for the treatment of influenza in the aspects of dosage form,category and prescription drugs. The network module partitioning method was used to excavate the core drug combination for influenza. The relationship between functional nouns was used to construct a network of functional terminology and analyze the relationship between its main functions. The pharmacological characteristics quantitative method was used to analyze the pharmacological characteristics of three heat-clearing and detoxifying type Chinese patent medicines for influenza. This article shows the traditional Chinese medicine syndrome differentiation ideas and medication rules for influenza treatment in many aspects and from multiple perspectives,so as to provide a certain reference for the clinical application of proprietary Chinese medicines for influenza and the development of new influenza drugs.

[Core prescription excavation of launched Chinese patent medicines for treating different syndromes of angina pectoris].

To analyze the medication features and regularity of prescriptions of traditional Chinese medicines in treating patients with coronary heart disease angina pectoris based on the launched Chinese patent medicines. In the article,we collected all of the launched Chinese patent medicines for treating coronary heart disease and angina pectoris from the Chinese patent medicine value assessment information database,and set up a medical record normalized database,then carried out the classification of syndromes. The medication features and prescription rules for angina pectoris were analyzed by frequency statistics and association rules(IBM SPSS Modeler 14. 1 Premiums software,Apriori algorithm). Finally,a total of 170 prescriptions were selected,and 197 Chinese herbs were included,involving to totally 11 syndrome types,in which blood stasis syndrome,Qi stagnation and blood stasis syndrome,Qi deficiency and blood stasis syndrome,Qi-Yin deficiency and blood stasis syndrome were the main syndrome types. The frequency of single-herb medicines for the four main syndrome types,the combination of commonly used medicines,and the core prescriptions were summarized. After comparing the core prescriptions of the four syndrome types,we could analyze the medication features and prescription rules. In conclusion,the therapeutic principle is blood-activating and stasis-dissolving,and consideration was also given to promoting Qi,invigorating Qi and resuscitation and invigorating Qi-Yin. The main medicines include Danshen(Salvia Miltiorrhizae Radix et Rhizoma) and Chuan-xiong(Chuanxiong Rhizoma). According to different types of syndromes,Chinese herbal medicines are added,such as Jiangxiang(Dalbergiae Odoriferae Lignum), Chishao(Paeoniaeradix Rubra), Sanqi(Notoginseng Radix et Rhizoma), Honghua(Carthami Flos),Bingpian(Borneolum Syntheticum),Renshen(Ginseng Radix et Rhizoma). Frequency statistics and association rules are combined to explore the medication features and core prescriptions,which provide ideas for the treatment of angina pectoris and the development of new drugs.

Development of Fangjiomics for Systems Elucidation of Synergistic Mechanism Underlying Combination Therapy.

The rapid development of omics technology provides an opportunity for fulfilling the understanding of the synergistic mechanism of combination therapy. However, a systems theory to analyze synergy remains an ongoing challenge. Fangjiomics is a novel systems science based on a holistic theory integrated with reductionism which has been utilized to systematically elucidate the synergistic mechanisms underlying combination therapy using multi-target-, pathway- or network-based quantitative methods. Besides, our ability to understand the polyhierarchical structure in synergy is driven based on multi-level omics data fusion in Fangjiomics. According to the basic principle of "Jun-Chen-Zuo-Shi", further global integration across various omics platforms and phenotype-driven quantitative multi-scale modeling would accelerate development in Fangjiomics-based dissection of synergy in multi-drug combination therapies.