Ticagrelor regulates the differentiation of MDSCs after acute myocardial infarction to reduce cardiac injury.

Myeloid-derived suppressor cells (MDSCs) are important participants after acute myocardial infarction (AMI), but the role of their different subtypes in AMI remains controversial. The anti-inflammatory effect of ticagrelor in AMI has been discovered. However, the detailed anti-inflammatory mechanism has not been fully demonstrated. In this study, we aimed to determine whether ticagrelor can regulate the differentiation of MDSCs into anti-inflammatory subgroups to exert anti-inflammatory effects after AMI. In vitro experiments revealed no difference in the mRNA and protein expression of P2Y12 receptors on MDSCs and macrophages. Ticagrelor promotes the differentiation of in vitro cultured MDSCs to monocytic-MDSCs (M-MDSCs). A mouse AMI model was established to investigate the anti-inflammatory effects of ticagrelor in vivo after AMI by interfering with the differentiation of MDSCs. On the first day after AMI, spleen-derived polymorphonuclear-MDSCs (PMN-MDSCs) were predominant in the circulation and infarcted heart. Ticagrelor increased the percentage of M-MDSCs in the circulation and infarcted heart of AMI mice in a dose-dependent manner, attenuated cardiac inflammation and increased cardiac contractile function. M-MDSC injection significantly decreased cardiac inflammation levels and improved cardiac function in splenectomized AMI mice compared with PMN-MDSC injection. These data point to a novel anti-inflammatory role for ticagrelor after AMI by interfering with the differentiation of MDSCs.

Network pharmacology-based prediction and verification of the active ingredients and potential targets of Huagan Decoction for reflux esophagitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Huagan Decoction (HGD), a famous traditional Chinese medicine (TCM) formula, has been widely used in the treatment of reflux esophagitis (RE). However, its effective compounds, potential targets and molecular mechanism remain unclear. AIM OF THE STUDY: To investigate effective compounds, potential targets and molecular mechanism of HGD against RE by using network pharmacology combined with in vitro validation, with the aims of observing the action of HGD and exploring new therapeutic strategies for RE treatment. MATERIALS AND METHODS: Effective compounds and potential targets of HGD, as well as related genes of RE, were collected from public databases. Pharmacological clustering and Gene Ontology (GO) enrichment analysis were applied to find targets that involving in the anti-inflammatory module. The pathways were drawn using Cytoscape 3.8.0. Important ingredients, potential targets, and signaling pathways were determined through the construction of protein-protein interaction (PPI), GO and Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, cell experiments were carried out. RESULTS: A total of 54 active ingredients and 240 RE-related gene targets of HGD were identified. The active compound-target network was visualized and pharmacological clustering further sorted 53 proteins that involve in the regulation of inflammatory responses. GO analysis confirmed the classification was statistically significant. Analysis of compound-target network revealed that quercetin and geniposide may be key ingredients for the anti-inflammatory effect of HGD against RE. The potential targets regulated by HGD are IL-6, IL-1ß, PTGS2, AKT1, TNF-α, MAPK1, IL-8, IL-10, CCL2 and MAPK3. In vitro experiment showed that quercetin and geniposide could inhibit the inflammatory response of HET-1A cells through p38MAPK/NF-κB signaling pathway, which was consistent with the prediction by the network pharmacology approach. CONCLUSIONS: Geniposide and quercetin could be effective therapeutic ingredients for the HGD against RE. They play anti-inflammatory effects via down-regulating the pro-inflammatory cytokines and the conduction of p38MAPK/NF-κB signal. This research provides a comprehensive study on the active components, potential targets, and molecular mechanisms of HGD against RE. Moreover, the study supplies a feasible approach to reveal the mechanisms of TCM formula.

[Quality value transfer of substance benchmarks in Sanpian Decoction].

According to the polarity of different components in Sanpian Decoction, two fingerprints were established. Then the substance benchmark freeze-dried powder of 15 batches of Sanpian Decoction was prepared, followed by the determination of the fingerprints, index component content, and dry extract rates, the identification of attribution of characteristic peaks, and the calculation of similarities between these fingerprints and the reference(R), the content and transfer rate ranges of ferulic acid, sinapine thiocyanate, liquiritin, and glycyrrhizic acid, and the dry extract rate range. The results showed that the similarities of 15 batches of the substance benchmark fingerprints with R were all greater than 0.900.Further summarization of the characteristic peaks revealed that there were a total of 20 characteristic peaks in fingerprint 1, among which, eight were from Sinapis Semen, four from Paeoniae Radix Alba, six from Chuanxiong Rhizoma, and two from Glycyrrhizae Radix et Rhizoma. A total of 16 characteristic peaks were observed in fingerprint 2, including one from Sinapis Semen, three from Paeoniae Radix Alba, eight from Chuanxiong Rhizoma, and four from Glycyrrhizae Radix et Rhizoma. The average dry extract rate of 15 batches of substance benchmarks was 18.25%, with a dry extract rate range of 16.28%-20.76%. The index component content and transfer rate ranges were listed as follows: 0.15%-0.18% and 38.81%-58.05% for ferulic acid; 0.26%-0.42% and 36.51%-51.02% for sinapine thiocyanate; 0.09%-0.15% and 48.80%-76.61% for liquiritin; 0.13%-0.24% and 23.45%-35.61% for glycyrrhizic acid. The fingerprint, dry extract rate, and index component content determination was combined for analyzing the quality value transfer of substance benchmarks in the classic prescription Sanpian Decoction.The established quality evaluation method for the substance benchmarks was stable and feasible, which has provided a basis for the quality control of Sanpian Decoction and the follow-up development of related preparations.

[Application progress on taste evaluation methods for oral preparations].

Taste is an important factor affecting the medicinal properties of oral preparations and patient compliance with medication, and also an important evaluation index for oral preparation design and clinical application. How to characterize the taste objectively, accurately, simply, and efficiently is a bottleneck problem that restricts the taste design, development, and utilization of oral preparations. At present, the commonly used taste assessment methods for oral preparations are traditional human taste panel, electronic tongue, animal preference test, in vitro release study, and electrophysiological test. The traditional human taste panel is the first choice for taste evaluation, but it is limited by poor subjectivity and reproducibility. Therefore, despite some limitations, the other four taste assessment methods have been applied in the pharmaceutical industry as auxiliary methods. This study reviewed the detection principles, applicability, advantages, and disadvantages of the above methods to provide references for the taste correction research and taste assessment of oral preparations, improve patient compliance and the competitiveness of oral preparation products in the industry, and promote the development of oral preparation technologies.

[Analysis on quality value transmitting of substance benchmark of Houpo Wenzhong Decoction].

By preparing 15 batches of lyophilized powder samples of substance benchmark in Houpo Wenzhong Decoction,the fingerprint,index component content and extract rate were determined,and the characteristic peaks,the range of similarity with the reference map,the content range and transfer rate range of magnolol,hesperidin,glycyrrhizic acid and pinocembrin,the extract rate range and the change range were clarified. The results showed that the similarity between the fingerprint of substance benchmark and the reference map R generated from the 15 batches of substance benchmark samples was higher than 0. 90. The assignment of the characteristic peaks in the full prescription's fingerprint of the herbs except Poria cocos was clarified. Nineteen characteristic peaks were assigned,and 12 characteristic peaks were assigned by the reference substance,of which 4 were from Magnolia ocinalis Cortex,5 from Exocarpium Citri Rubrum,2 from Radix aucklandiae,3 from Glycyrrhiza Radix et Rhizoma,4 from Semen Alpiniae Katsumadai,and one from Rhizoma Zingiberis and Zingiber officinale Roscoe. The index component content range and transfer rate range were 0. 80%-1. 14% and 20. 25%-39. 61% for hesperidin,0. 49%-0. 79% and 23. 09%-33. 87%for glycyrrhizic acid,0. 03%-0. 07% and 3. 55%-10. 09% for pinocembrin,0. 15%-0. 38% and 8. 08%-24. 35% for magnolol. The extract rate range and the change range were22. 60%-25. 57% and 12. 67%-23. 68% respectively. In this study,we introduced the concepts of index component content,fingerprint,extract rate,explored the transfer relation of quality value transmitting of substance benchmark in Houpo Wenzhong Decoction,and initially established the quality standard of Houpo Wenzhong Decoction,all of which would provide ideas for the development and research of similar prescriptions.