Fructose 1, 6-bisphosptase (FBPase), a second rate-limiting enzyme in gluconeogenesis, has an important role in the control of gluconeogenesis, which involves in energy metabolism and glucose homeostasis. Inhibitors of FBPase exhibit an anti-diabetic activity. Some of FBPase inhibitors have entered the stage of clinical trials, which indicates that FBPase is a promising therapeutic target for the discovery and development of hypoglycemic drugs. In addition, recent studies have shown that FBPase can be used to treat other diseases such as the initiation and development of tumors in several cancer types. Here, we provide a review of the biological characteristics of FBPase and contributions of FBPase on gluconeogenesis and insulin secretion, the research and development of FBPase inhibitors and the regulatory role of FBPase in other diseases.

This study was designed to explore the impact of Huanglian Jiedu Decoction (HLJDT) on macrophage inflammation reaction using the network pharmacology method. Glycolysis, sphingolipid metabolism and glutamine metabolism were also investigated for "multi-component, multi-target and multi-pathway", which supports a foundation for drug innovative research. The TCMSP database was used to screen the active components of HLJDT, the target protein predicted by PharmMapper database and the DAVID database for pathways annotation and analysis. The Cytoscape 3.2.1 software was used to construct the active componenttarget-pathway network map and GENEMANIA database for protein interaction analysis. System Dock Database Site is used in verification of molecular docking. The results showed that 84 active ingredients were screened in HLJDT with a total of 111 target targets. Fourteen pathways are affected according to 13 macrophage-related inflammatory proteins, and 8 pathways including 34 target proteins from glycolysis, sphingolipid metabolism and glutamine metabolism. Inflammation-related proteins and metabolism-related proteins can interact with each other through physical correlation, protein co-expression, etc. Berberine, baicalin and geniposide combined well with 5 important targets. Huanglian Jiedu Decoction may act on the glycolysis and sphingolipid pathways to regulate macrophage inflammatory responses.

The study was designed to explore the active components and mechanism of Kai Xin San in the treatment of Alzheimer's disease (AD) based on network pharmacology. All targets related to AD were researched in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Therapeutic Targets Database (TTD). The common targets obtained by two databases were determined as candidate proteins involved in AD. All active components related to Kai Xin San were researched from ADME (absorption, distribution, metabolism and excretion). PharmMapper was used to obtain the primary candidate targets of Kai Xin San. The corresponding gene name of each target protein was obtained from the UniProt database and selected human target proteins. Finally, the target proteins related to AD by Kai Xin San were acquired; Cytoscape 3.5.1 was used to construct the topology analysis for the active ingredient-AD target interaction network of Kai Xin San. According to STRING database and DAVID annotation databases, Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the targets was performed. The network pharmacology analysis results were verified by Discovery Studio molecular docking software. There were 31 components meeting the conditions of ADME and 8 targets relating to AD. Thirteen kinds of biological process, 7 related to molecular function and 11 related to cellar components, were included in 31 GO entries. There were 5 KEGG pathways, involving the calcium signaling pathway and PI3K-Akt signaling pathway. The docking results of Discovery Studio showed that active ingredients of Kai Xin San and the positive controls all have good binding activity with important targets. In conclusion, the Kai Xin San as applied for treating AD has the advantages of multi-components and targets, to investigate the active components and mechanism of Kai Xin San for treating AD based on network pharmacology to eludicate possible studies of the mechanisms of action.

Hemorrhagic transformation (HT) is a common complication of ischemic stroke, especially after thrombolytic therapy, which is associated with increased morbidity and mortality. Thrombolysis with tissue plasminogen activator (t-PA) increases the rate of HT by as much as 10-fold, and the mortality by about 60%. The patients who are eligible for t-PA treatment are still between 3.4% and 5.2% of all patients with acute ischemic stroke because of the narrow therapeutic time window. Due to the unknown mechanism and therapeutic target of HT, there are no effective drugs to decrease the incidence of HT. The main mechanism of HT is disruption of the blood-brain barrier (BBB) integrity and neurovascular homeostasis, involving a variety of molecular signaling pathways. In animal and clinical studies, combining therapeutic agents with t-PA, which may help to minimize BBB perturbations, reduces the incidence of HT and increases the safety of thrombolytic therapy. This article is prepared to review the mechanisms, targets and therapeutic drugs of t-PA induced HT in recent years to provide a reference to the basic research and drug development of HT.

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 SystemsDock. 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.

Jiawei Foshou San is a new Chinese medicine compound consisting of ligustrazine, ferulic acid and fumarate. Previously Jiawei Foshou San inhibited the growth of endometriosis with unclear mechanism, especially in metastasis and invasion. In this study, network pharmacology analysis was performed to explore potential mechanism of Jiawei Foshou San on endometriosis. Jiawei Foshou San compound targets were purchase from TCMID, TCMSP and SEA database. Endometriosis targets were collected from OMIM, DisGeNET and GEO database. Networks of Jiawei Foshou San compound-compound targets and compound target-endometriosis target were established with Cytoscape 3.5.0 software. Key targets were analyzed for pathway enrichment through DAVID database. It was found that Jiawei Foshou San regulated 66 core targets (MMP2, MMP9, TIMP1, ICAM1, VEGFA, et al.) and affected 115 pathways, such as estrogen, HIF-1, TNF and GnRH signaling pathways. MMP-TIMP were uncovered as one cluster of the core targets. Furthermore, Jiawei Foshou San significantly suppressed the growth of ectopic endometrium. Meanwhile, invasion and metastasis were restrained after treating with Jiawei Foshou San through decreasing MMP-2 and MMP-9, increasing TIMP-1. In brief, these results provide a pharmacodynamic basis for the study of Jiawei Foshou San.

Gold nanoclusters (AuNCs) are gold atom aggregates less than 2 nm (excluding the ligand shell) or 150 atoms. It has been widely studied due to its small size effect, fluorescence property, and catalytic activity. In this review, research progress in the preparation of gold nanoclusters containing accurate atom numbers using biomolecules and chemically synthesized molecules as ligands have been summarized. The factors that affect the preparation of gold nanoclusters have been discussed. The applications of AuNCs having accurate atomic numbers in the fields of analyte assay, catalysis, bioimaging, and drug delivery have been introduced. This review provides references to the further researches on the preparation technology and biomedical applications of AuNCs.

By using the integrated 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, essential oil, fatty acids and so on. 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 active modified protein (RAMP), platelet growth factor receptor (PDGFR), insulin receptor (INSR), α-glucosidase (GAA), etc. The pathways with diabetes effect involves 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-3β (GSK-3β), 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 complex prescription.

Seven cucurbitane-type triterpenoids were isolated from the ethanol extract of the tubers of Hemsleya dolichocarpa, with a combination of various chromatographic approaches, including silica gel, Sephadex LH-20, Semi-HPLC and so on. On the basis of spectroscopic data analysis, they were identified as 3β, 11α, 26, 27-tetrahydroxycucurbita-5, 24(E)-diene-3, 26-glucosides (1), scandenogenin D (2), jinfushanencin F (3), scandenoside R3 (4), scandenoside R₁ (5), scandenogenin A (6), scandenoside R₂ (7). Among them, compound 1 is a new triterpenoid, compound 2 showed remarkable activity against human cancer cell line HeLa with IC₅₀ value of 6.78 μmol·L^-1.

The purpose of this research is to investigate the effects and mechanisms of paeonol (PL), a phenolic compound found in many traditional Chinese formulations, on reversing drug resistance in the ovarian cancer resistant SKOV3/DDP cells. The results showed that PL had significant drug-resistant reversal effect on SKOV3/DDP cells. Flow cytometry showed that PL could inhibit P-glycoprotein (P-gp) function in a concentration-dependent manner. Fluorescent quantitative PCR and cell immunofluorescence techniques were used to detect mechanisms of action. Results revealed that both the inhibitory effect on MDR1/P-gp and metadherin (MTDH) expression and the induction effect on phosphatase and tensin homolog (PTEN), by 15, 30, and 60 μmol·L^-1 PL, were increased with increased concentrations of PL (P < 0.01, P < 0.05). The inhibitory effect on MTDH mRNA and the induction effect on PTEN mRNA, by PI3K inhibitor LY294002, were stronger or equivalent to that of the 60 μmol·L^-1 PL treated group; however, the inhibition or induction effect on MTDH or PTEN protein were only comparable to the 15 μmol·L^-1 PL treated group. The present study shows that the effect of PL on SKOV3/DDP cells may be related to the inhibition of P-gp function and expression, the inhibition of MDR1, MTDH expression, and the induction of PTEN expression, all which can provide a theoretical foundation for PL as a drug resistance reversal agent on the treatment of ovarian cancer chemotherapy resistance.