World Chinese Medicine,Part 1: Theoretical Analysis,Vol 14,No. 01
Glucolipid Metabolic Disorders (GLMD) is a disease with the metabolic disturbance of glucose and lipid, influenced by genetic, environmental and mental factors. The significant pathology phenomena of GLMD are the neuroendocrine dysfunction, insulin resistance, inflammation and the alteration of intestinal flora. Meanwhile, there are clinical manifestations like hyperglycemia, dyslipidemia, non-alcoholic fatty liver disease, obesity, hypertension and atherosclerosis showing up singly or going with each other. Prof. Guo Jiao and her team put forward the way of regulating liver to resolve turbidity as a new train of thought for therapies of GLMD, based on systematic literature reviews in traditional Chinese medicine and clinical researches, which worked prominently in experiments and clinical researches. However, there is still no biological definition of “turbidity”. With the assistance of modern bio-technologies like multi-omics and phenotypic identifications of modified animal, it has been confirmed that metabolic inflammation mediated by innate immunity is one of the most vital pathological mechanisms in the process of GLMD. This article is to discuss the biological definition of “turbidity” in GLMD through the innate immune cells (mainly including macrophage and neutrophils) also with its key mediated factor (Toll-like receptor 4, Lipocalin-2), and it is important for uncovering the substance of “turbidity” and the material base of decoctions for resolving turbidity.
Acta Pharmaceutica Sinica,Part 1: Theoretical Analysis,Vol 52,No. 02
Property and flavor theory of traditional Chinese medicine (TCM) is the core base for clinical treatment of diseases. However, few research about its chemical and biological characterization was performed. In this paper, network pharmacology was adopted to review patterns around the theory of TCM. “Xiaoke” prescription database, which combinations of herb medicines for diabetes therapy, was firstly built to explore prescription regularity and screen core paired-components. The prescription regularity and molecular mechanism of flavor composition were explored through the relationship of “drug–compound–target–pathway–function” by Ch EMBL, CTD and KEGG datebase. As a result, the tastes of “Gan” (sweetish taste) and “Ku” (bitter taste) were the popular therapeutic flavor to regulate the disorder of glucose and lipid metabolisms. The mechanism of Xiaoke was summarized from representative traditional Chinese medicine partner “Zhimu–Huangbai” and “Huangqi–Gegen”. The key components of “Gan”,including saponins stimulated insulin secretion, improve insulin resistance and promote glucose utilization. The components of “Ku”, including flavonoids and alkaloids regulate inflammatory cytokines,promoted the utilization of glucose, improve endocrine and metabolism through MAPK, PI3K-Akt, PPAR signal pathway. The TCM therapeutic mechanism about “Xiaoke” was preliminarily summarized to clear “heat” by anti-inflammation and immunoregulation, to regulate glucolipid metabolism for removing the satiation of digestion, and to improve the utilization of insulin and diabetes complications for endocrine adjusting. The results demonstrate that therapeutic principle of TCM for “Xiaoke” is comprehensive via multi pathway. This study provides a new research method and strategy for exploring the mechanism of TCM for diabetes therapy.
Chinese Traditional and Herbal Drugs,Part 1: Theoretical Analysis,Vol 49,No. 03
Objective To investigate the active ingredients and molecular mechanism of Radix Astragali seu Hedysari, Radix Angelicae Sinensis, Radix Angelicae Dahuricae, and Gleditsia sinensis in Tuoli Xiaodu Powder in promoting of diabetic wound healing.
Methods UPLC-Q-TOF/MS in positive and negative ion modes was applied to analyze the components in the ethanol extract from Tuoli Xiaodu Powder. Molecular docking technology was used to predict the targets proteins of these components. The function and pathway annotations of target proteins were performed through relevant databases such as Uniprot and KEGG. The drug components-target-function diagram was constructed using Cytoscape software.
Results Twenty-eight compounds containing flavonoids, saponins, coumarins, alkaloids, and triterpenoids were identified in positive and negative ion modes. Among these compounds, 17 compounds could interact with 17 target proteins, and there were 210 pairs of component-target relationships by analyzing the results of molecular docking. Among them, five targets were related to immune regulation, six targets were related to antibacterial and anti-inflammatory effects, six targets were related to cell differentiation, 10 targets were related to cell migration, six targets were related to angiogenesis, two targets were related to stimulation of epithelial growth factor, six targets were related to vasodilation, and two targets were related to estrogen.
Conclusion The flavonoids, saponins, coumarins, steroids, and triterpenoids contained in the simplified formula possess many biological effects such as antibacterial, anti-inflammatory, immune regulation, and angiogenesis. These functions may be related to its modulation of NF-κB, PI3 K/Akt/eNOS, and MAPK pathway through regulating NF-κB, MAPK, PI3K, and ERK2 targets.
Acta Pharmaceutica Sinica,Part 1: Theoretical Analysis,Vol 53,No. 04
The aim of this study was to discover the pharmacological mechanism of Compound Xueshuantong in the treatment of diabetic retinopathy using network pharmacology. TCMSP software was used to search the active ingredients of Compound Xueshuantong, and the targets of its active ingredients were obtained. The targets of diabetic retinopathy were searched by OMIM, TTD, pharmGkb, DiGSeE and GAD database. The same 37 targets were analyzed by GO and KEGG using DAVID software. The results were verified using the Systems Dock. Cytoscape 3.6.1 software was used to establish an ingredient–target–pathway network model. Network pharmacological studies suggest that Compound Xueshuantong treated diabetic retinopathy through the vascular endothelial growth factor signaling pathways, mitogen-activated protein kinase signaling pathways and Toll-like receptor signaling pathways. Compound Xueshuantong alleviated diabetic retinopathy through multi-component, multi-target, and multi-pathway. This study provides a theoretical basis for further elucidation of the pharmacological mechanism of Compound Xueshuantong in the treatment of diabetic retinopathy.
Acta Pharmaceutica Sinica,Part 1: Theoretical Analysis,Vol 53,No. 05
By using the integrative pharmacology platform and the big data of traditional Chinese medicine combined with the pharmacology thinking of “principle-recipe-composition-target-pathway-activity” in this study, we predicted the material basis and mechanisms of Bupleuri Radix and Scutellariae Radix drug pair for the treatment of diabetes. Fifty-nine active components were predicted, which included saponins, flavones, volatile oil, fatty acids, etc. They acted on twenty-two direct targets and twenty-six main pathways respectively. The known disease targets of diabetes include arginine vasopressin receptor gene (AVP), retinoblastoma (RB1), receptor activity-modifying protein (RAMP), platelet growth factor receptor (PDGFR), insulin receptor (INSR), α-glucosidase (GAA), etc. The pathways with diabetes effect involve endocrine system, circulatory system, digestive system, thyroid hormone signaling pathway, ErbB signaling pathway, PI3K-Akt signaling pathway, lipid metabolism and other related biological processes and metabolic pathways. The results of virtual screening in molecular docking technology indicate that flavonoids from Bupleuri Radix and Scutellariae Radix drug pair can easily form good docking mode and high affinity with peroxisome proliferators activated receptor
γ (PPAR-
γ) and glycogen synthase kinase-3
β (GSK-3
β), showing antidiabetic activity. The study provides information for the treatment of diabetes by Bupleuri Radix and Scutellariae Radix drug pair, and a new thought for the study of drug pair and compound prescription.
China Journal of Chinese Materia Medica,Part 1: Theoretical Analysis,Vol 44,No. 06
Chemical constituents of the Fufang Huangbai Ye were analyzed and identified by UPLC-ESI-LTQ-Orbitrap MS. The analysis was performed on an Waters HSS T3 reverse phase column (2.1 mm × 100 mm, 1.8 μm). The mobile phase consisting of 0.1% aqueous formic acid (A) and acetonitrile (B) was used with gradient elution, and the flow rate was 0.3 mL·min
?1. Based on the information of the accurate mass, the multistage fragment ions, the mass spectrometric data of the standard substance and the relative reference literature, the structure of the chemical constituents in Fufang Huangbai Ye were identified. Based on the identified compounds, network pharmacology study, including target prediction, functional enrichment, and molecular docking was applied to screen out the main active substances for treatment of diabetes foot and explore the potential mechanism. The results showed that a total of 138 compounds were identified, including 28 alkaloids, 16 flavonoids, 11 phenylethanoid glycosides, 9 cycloolefins, 11 cyclohexylethanol derivatives, 28 phenolic acids and derivatives, 3 lignans, 4 terpenes, 28 volatile oils and the others. Further, 36 active substances for diabetes foot were screened out, and the functional enrichment showed the potential mechanism of Fufang Huangbai Ye were mainly seven functional items including inflammatory response, growth factor activity. This study combining the UPLC-LTQ-Orbitrap-MS technology and the network pharmacology provide a useful reference and basis for active compounds, quality control markers and the pharmacological mechanism of Fufang Huangbai Ye for diabetic foot treatment.
Chinese Traditional and Herbal Drugs,Part 1: Theoretical Analysis,Vol 50,No. 07
Objective In this paper, herb-component-common target network and protein interaction network were constructed to study the common mechanism of Xiaoyao Powder in the treatment of depression combined with diabetes from the perspective of “treating different diseases with the same method”.
Methods TCM database@Taiwan, TCMID, and Batman-TCM databases were searched and the literature search was conducted to obtain the components and targets of Xiaoyao Powder, and the targets for Xiaoyao Powder in the treatment of depression combined with diabetes were figured out based on CTD, TTD, PharmGKB, OMIM, Gencards, and Drugbank databases. The Cytoscape was applied to plot the herb-component-common target network. The Metascape was used for GO biological process, Reactome pathway, and KEGG pathway analysis, protein interaction network construction and module analysis of the common targets of Xiaoyao Powder in the treatment. The tissue distribution and subcellular distribution of key pathway targets were separately analyzed based on BioGPS and Genecard, and the tissue-target network and subcellular-target network were constructed by the Cytoscape. Protein classification of key pathway targets was performed by DisGeNET.
Results The results revealed that the treatment involved the immune and inflammatory responses, which was related to G protein-coupled receptors, insulin and its receptors, and monoamine neurotransmitters, and the efficacy was achieved by regulating cAMP signaling pathway, calcium signaling pathway and PI3 K-Akt signaling pathway.
Conclusion The mechanism of Xiaoyao Powder in the treatment of depression combined with diabetes involved the regulation of brain-derived neurotrophic factor (BDNF) signaling pathways, G protein-coupled receptors, monoamine neurotransmitters and insulin and its receptors, which has provided reference for further investigation on antidepressant characteristics of Xiaoyao Powder and its pharmacological mechanism.
Chinese Pharmacological Bulletin,Part 1: Theoretical Analysis,Vol 36,No. 08
Aim To explore the main components and anti-inflammatory mechanisms of essential oil from
Schizonepeta tenuifolia Briq. based on network pharmacology.
Methods TCMSP and Swiss Target Prediction were used to obtain the corresponding targets of molecules, and the active components were screened. The molecular-target network was constructed. Then, protein-protein interaction (PPI) analysis, GO analysis, and KEGG pathway analysis were performed. Finally, molecular docking by SystemsDock was combined with previous literature.
Results According to the results of network analysis, 13 main components corresponding to 45 targets were screened out. IL6, TNF, IL1β, IL10, PTGS2, PTGS1, CHRM1, and CHRNA7 were important inflammatory targets through NF-κB and IL-17 signaling pathway. Biological processes such as response to drug, γ-aminobutyric acid pathway, and molecular functions such as extracellular ligand-gated ion channel activity, GABA-A receptor activity play a role in inflammation related to alcohol consumption, type 2 diabetes, psychiatric disorders, enteropathy, lung diseases, etc. 8,9-dehydrothymol, benzaldehyde, caryophyllene, α-humulene, D-germacrene, and pulegone were important anti-inflammatory components, exerting significant effects on CHRNA7, PTGS2 and PTGS1.
Conclusion This method initially reveals the effective components and potential targets of essential oil from
Schizonepeta tenuifolia Briq.
