Research progress on endogenous small-molecule phenolics and the proposal of "phenolomics" / 药学学报

Small-molecule phenolic substances widely exist in animals and plants, and have some shared biological activities. The metabolism of phenylalanine and tyrosine in the human body, and especially the metabolism of catecholamine neurotransmitters, produces endogenous small-molecule phenols. Endogenous small-molecule phenolic substances are functionally related to the important physiological processes and the occurrence of mental diseases in humans and some animals, which are systematically sorts and summarized in this review. Integrating the previous experimental research and literature analysis on natural small-molecule phenols by our research group, the understanding of the hypothesis that "small-molecule phenol are pharmacological signal carriers" was deepened. Based on above, the concept of "phenolomics" was further proposed, analyzed the research direction and research content which can bring into the knowledge framework of phenolomics. The induction of phenolomics will provide wider perspectives on explaining the pharmacological mechanism of drugs, discovering new drug targets, and finding biomarkers of mental diseases.

Mechanism of hepatotoxicity induced by ethanol extract of Dysosma versipellis based on "quantity-weight-evidence" network toxicology / 中国中药杂志

In this study, the toxicological/pharmacological research method of "quantity-weight-evidence" network was first proposed and practiced to supplement the existing methodology of network toxicology. We transformed the traditional qualitative network into a quantitative network in this study by attributing weights to toxic component content and target frequency, which improved the reliability of data and provided a research idea for the systematic safety evaluation and toxicological research of Chinese medicinal herbs. Firstly, 50% ethanol extract of Dysosma versipellis(DV) was administrated to rats via gavage and the potential hepatotoxic components were identified by serum pharmacochemistry. Then, the component targets were obtained from SwissTargetPrediction, PharmMapper and other online databases, and the target weights were given according to the relative content of components and target fishing frequency. Meanwhile, the targets of hepatotoxicity were predicted from online databases such as Comparative Toxicology Database(CTD) and GeneCards. Subsequently, protein-protein interaction analysis and KEGG pathway enrichment were performed with the STRING database. Finally, the quantitative network of "toxic components-weighted targets-pathways" was constructed. Eleven potential toxic compounds were predicted, including podophyllotoxin, podophyllotoxone, deoxypodophyllotoxin, and 6-methoxypodophyllotoxin. A total of 106 hepatotoxic targets and 65 weighted targets(e.g., Cdk2, Egfr, and Cyp2 c9) were identified. The results of Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment showed that these targets could act on PI3 K-AKT, MAPK, and Ras signaling pathways to play a role in inflammatory response and oxidative stress. However, traditional network toxicology showed that 51 targets such as AKT1, Alb, and Stat3 may lead to hepatotoxicity by mediating inflammation and cell proliferation. In conclusion, we proposed "quantity-weight-evidence" network toxicology in this study and used it to study the mechanism of DV-induced hepatotoxicity in rats. This study confirms the feasibility of this new methodology in toxicological evaluation and further improves the systematic evaluation of the safety of Chinese medicinal herbs.

Meta-analysis of Danhong Injection in treatment of diabetes mellitus complicated with coronary heart disease / 中国中药杂志

To systematically evaluate the clinical efficacy and safety of Danhong Injection combined with conventional therapy in improving diabetes mellitus complicated with coronary heart disease. Based on the online literature database(CNKI, Wanfang, VIP, PubMed, Web of Science, Cochran Library), the Chinese and English papers about the randomized controlled trial(RCT) of Danhong Injection in the treatment of diabetes mellitus complicated with coronary heart disease were searched comprehensively from the establishment of the databases to January 1, 2020. The papers were screened strictly according to the inclusion and exclusion criteria. Based on Jadad scale, the risk assessment of literature was carried out, and Meta-analysis was performed by STATA 12.0 software. Seventeen RCTs were included, involving 1 453 patients. The results of Meta-analysis showed that the combination of Danhong Injection and conventio-nal treatment could improve the clinical comprehensive effective rate(RR=1.47, 95%CI[1.38, 1.58], P<0.000 1), electrocardiogram(ECG) efficiency(RR=1.30, 95%CI[1.16, 1.46], P<0.000 1), efficiency of the angina pectoris(RR=1.41, 95%CI[1.25, 1.58], P<0.000 1), cholesterol level(SMD=-1.05, 95%CI[-1.95,-0.16], P=0.02), low-density lipoprotein(LDL) level(SMD=-0.50, 95%CI[-0.79,-0.21], P<0.000 1), coronary angina attack frequency(SMD=-3.71, 95%CI[-4.05,-3.36], P<0.000 1) and duration of angina pectoris(SMD=-2.96, 95%CI[-3.25,-2.66], P<0.000 1), with statistically significant differences. But the differences in fasting plasma glucose(FPG)(SMD=-0.19, 95%CI[-0.45, 0.08], P=0.16), plasma glucose of two hours after meal(2 hPG)(SMD=0.19, 95%CI[-0.11, 0.49], P=0.22), and high-density lipoprotein(HDL) level(SMD=0.10, 95%CI[-0.30, 0.49], P=0.62) after treatment were not statistically significant. Compared with the control group, there was no significant difference in adverse reactions(SMD=-2.96, 95%CI[-3.25,-2.66], P=0.75). The existing evidence shows that the combination of Western medicine and Danhong Injection can improve the clinical effect for diabetes mellitus complicated with coronary heart disease and has no obvious adverse reactions. However, due to the low level of overall literature evidence, high risk and some kind of publication bias, it still needs more high-quality randomized controlled trials and low-bias studies for further verification.

[Analysis of potential pharmacodynamic material basis of Euonymus alatus in treatment of nephritis based on integrated chemomics and network biology].

This paper was aimed to explore the potential pharmacodynamics effect of Euonymus alatus in the treatment of nephritis based on integrated chemomics and network biology. The chemical constituent database of E. alatus was constructed by consulting litera-ture and using online database. The chemical constituents were identified by UPLC-Q-TOF/HRMS~E and UNIFI software. On this basis, a series of comparisons, molecular docking studies and in-depth analysis of the chemical constituents and nephritis disease targets were carried out with use of network biology method, and the potential pharmacodynamic effect of E. alatus for the treatment of nephritis was investigated by reviewing the existing. In this study, 62 chemical constituents were collected in the database of chemical consti-tuents of E. alatus, and 24 chemical constituents were identified by mass spectrum. Subsequently, based on the network biology me-thod, 22 important chemical constituents and 5 key targets were obtained by reverse screening. Molecular docking study showed that a total of 11 chemical constituents such as quercetin, kaempferol, and catechinmay be the potential material basis for E. alatus in the treatment of nephritis. Starting with chemomics and using the technology of network biology, we established a network interaction model between drug components and disease targets in this study. Through the interaction between targets in complex networks, we can find the key targets easily and quickly. By docking the key targets with small drug molecules, we can screen out the potential pharmacodynamic components, providing a reference for the follow-up study of active ingredients.

Research progress on chemical composition and pharmacological effects of Periplocae Cortex and predictive analysis on Q-marker / 中国中药杂志

Periplocae Cortex is a traditional Chinese medicine in China, which is mainly produced in northeast China, north China, northwest China, southwest China. In recent years, the increasing in-depth research resulted in the discovery of anti-tumor and cardiac pharmacological activities of Periplocae Cortex, which has broad application prospects. On the basis of summarizing chemical components and pharmacological effects, combined with the theoretical system of Q-marker, the quality control components of Periplocae Cortex were predicted from the aspects of the correlation between chemical composition and traditional medicinal properties, traditional efficacy, and new clinical use, plasma composition, measurable composition, storage time by analyzing literature. Among the components, periplocoside, periplocin, periplogenin, 4-methoxy salicylaldehyde showed significant activity, which provides a scientific basis for quality evaluation of Periplocae Cortex.

Pharmacodynamic Basis of Jinqi Jiangtang Tablets in Treatment of Type 2 Diabetes Based on LC-MS and Molecular Docking Strategy / 中国实验方剂学杂志

Objective::Based on LC-MS and molecular docking strategy, to study the pharmacodynamic material basis of Jinqi Jiangtang tablets in the treatment of type 2 diabetes mellitus(T2DM). Method::UPLC-Q-TOF-MS was used to identify the chemical constituents of Jinqi Jiangtang tablets. On this basis, the disease targets were screened based on the online disease target database and protein-protein interaction(PPI). The molecular docking technology was used to verify the relationship between the chemical constituents and disease targets in Jinqi Jiangtang tablets, so as to find out the potential pharmacodynamic basis of Jinqi Jiangtang tablets in the treatment of T2DM. Result::Based on UPLC-Q-TOF-MS, 51 chemical constituents were identified in Jinqi Jiangtang tablets, including 31 astragalus, 16 coptis and 4 honeysuckle. The key targets of catalase from micrococcus lysodeiktic(CAT) receptor, peroxisome proliferative actived receptor(PPARG) receptor and insulin(INS) receptor were identified by CTD database, topological analysis and related literature. Based on LC-MS and molecular docking technology, we found that magnoflorine, coptisine, epiberberine, astragaloside Ⅳ, caffeic acid, palmatine, berberine, jateorhizine, berberubine, berberastine, groenlandne, lycoranine B, demethyleneberberine, isomucrontolula-7-O-glucoside and calycosin-7-O-glucoside were used to treat type 2 diabetes potential pharmacodynamic material basis of urinary diseases. Conclusion::Protein interaction and network topology analysis are helpful for the rapid localization of core targets. In addition, molecular docking technology can realize large-scale virtual screening of potential candidate compounds. The integration of LC-MS and molecular docking technology can facilitate and quickly find the potential pharmacodynamic substance basis in traditional Chinese medicine prescriptions, and provide a reference for subsequent drug activity screening experiments.