Latest ArticlesFebuxostat, as a xanthine oxidase inhibitor, is a classic anti-gout drug with significant therapeutic effects and good tolerability. The structures of febuxostat and its derivatives can be divided into two parts: a substituted phenyl ring and a five-membered or six-membered heterocyclic ring with a carboxyl substitution. This paper reviewed the research progress of febuxostat derivatives in recent ten years and classified the structure-activity relationships of various febuxostat derivatives. Exploring the action mechanisms and structure-activity relationships of xanthine oxidase inhibitors might be significant for the rational design and development of new anti-gout chemical entities.
The quality evaluation of compound Chinese medicines is an important but challenging issue in this research field, which has been paid much controversial due to the constrained association with clinical efficacy. Developing a methodology for quality evaluation of compound Chinese medicines related to clinical efficacy is an important measure in research on Chinese material medica quality to ensure clinical effectiveness and safety. Therefore, based on the research concept that "originating from clinic-testing in experiment-returning to clinic", and taking Xiaoke prescription as an example, the characteristic information of metabolome, proteome and microbiome are discussed from the clinical aspect, and the integrated markers associated with clinical efficacy constructed with artificial intelligence technology. Taking the integrated markers as the link and indication are connecting the clinical and basic, the main pharmacodynamic substances and key targets of Xiaoke prescription that are related to clinical efficacy are explained. Clinical samples are used for validation. Based on the main pharmacodynamic substances and key targets, methods and key technologies for chemical and biological evaluation of the quality of Xiaoke prescription are established, providing a methodology for quality evaluation of compound Chinese medicines, including clinical efficacy response indicators (related to clinic), main pharmacodynamic substances (chemical evaluation), and key targets (biological evaluation), to provide new ideas and methods for improving the quality evaluation of compound Chinese medicines.
Photodynamic therapy (PDT) is a therapeutic strategy by which photosensitizers are excited by specific light irradiation to produce singlet oxygen for killing the surrounding cells. The advantages of PDT include weak invasion, slight side effect, and low resistance. The advantages of nanoscale drug delivery systems (DDS) include tumor-targeting, sustained release, and environmental-sensitivity. The combination of PDT and nanoscale DDS would likely lead to tumor targeting of photosensitizers and enhance their antitumor effectiveness. This review discusses the mechanism of PDT, photosensitizer-loaded nanoscale formulations, the combination of PDT and other antitumor therapies, and summarizes the applications and prospects of anti-tumor nanoscale DDS based on PDT. This review is a useful reference for its clinical application.
In order to solve the problems of erratic drug absorption and low bioavailability after oral administration for poorly-water soluble drugs due to low solubility, a series of novel pharmaceutical dosage forms as solid dispersion, liposome, microemulsion, vesicle, cyclodextrin inclusion complexes and drug nanocrystal have been developed in recent years. Among which drug nanocrystal attracts more attentions for its simpler preparation method, higher drug loading and easier manufacturing technology in the design of dosage forms suitable for different administration routes. In this paper, the nanocrystals of the poorly-water soluble drugs prepared based on bottom-up and top-down technologies were introduced. The characteristics and applications of the nanocrystal-based dosage forms as suspension, tablet and capsule were also introduced and carefully evaluated with the focus on their pharmacokinetics, pharmacodynamics and tissue targeted drug distribution after delivery by oral administration, intravenous injection and pulmonary inhalation. The advantages of drug nanocrystals in their therapeutics effects over the bulk drugs were discussed together with the inherent mechanism. Finally, the problems existing in basic research and scaled-up manufacture of drug nanocrystal as well as the possible ways of solution were listed out so as to make the nanocrystal-based preparations exert their maximum therapeutic effect after clinical application.
Outer membrane vesicles (OMVs) are nano-sized spherical vehicles, with a size range between 20-250 nm. OMVs are spontaneously secreted from Gram-negative bacteria and formed by lipid bilayer membranes, comprising multiple parent bacteria-derived components including bacterial antigens, pathogen-associated molecular patterns, proteins and lipids. OMVs have shown multiple potentials for the treatment of various diseases, including cancer therapy and bacterial infection. In this review, the structure, composition and methods for isolating and characterizing of OMVs were introduced. The applications of OMVs for diseases therapy were summarized and future perspectives were discussed.
Poly (β-amino ester)s (PβAEs) contain tertiary amine backbones and biodegradable ester bonds, making them highly biocompatible and pH-responsive. Meanwhile, originated from combinatorial libraries, PβAEs are simple to synthesize, easy to obtain raw materials and can be easily adapted to meet the different performance needs of gene carriers by adjusting the monomer type, monomer ratio and reaction time. Therefore, PβAEs are promising material for non-viral gene carriers. This paper provides a comprehensive overview of the properties and synthesis of PβAEs gene carriers and summarizes the progress of research on the gene delivery of each type of PβAEs.
microRNA (miRNA) is a class of endogenous~21nt non-coding single-strand small RNAs which play important roles in plant growth and development, signal transduction, stress response, and secondary metabolism. In recent years, a large number of miRNAs have been identified in various medicinal plants, and the regulatory effects of these miRNAs have been preliminarily studied. In medicinal plants, most of the active components are secondary metabolites, so it is of great significance to study the regulatory effects of miRNA on the formation of secondary metabolites. In this paper, the general research methods of plant miRNA and the research progress of medicinal plant miRNA and their regulatory effects on the formation of bioactive metabolites were reviewed, and the future direction of medicinal plant miRNA was prospected, so as to provide reference for the future research of medicinal plants.
We explored the mechanism of patchouli oil in the treatment of inflammatory bowel disease (IBD) based on network pharmacology and differentially expressed genes in macrophages. The chemical composition of patchouli oil was detected by GC-MS, targets for active components were collected through TCMSP and Swiss Target Prediction platform, and targets for treatment of IBD were retrieved from DrugBank, GeneCards, OMIM, PharmGkb, and TTD databases. The intersection targets were merged, Cytoscape software was used to construct the "component-to-intersection target" network, and protein-protein interaction (PPI) network was drawn with String platform. The intersection targets were enriched for GO and KEGG enrichment analysis on Metascape platform, and the molecular docking of AutoDock Vina was used to verify the analysis results. The macrophage chip data was downloaded, and the differential genes were obtained by using R software. KEGG signaling pathway analysis of differentially expressed genes were performed by DAVID platform. Real-time fluorescence quantitative PCR was used to verify the screened components in the cell model in vitro. The 14 main components of patchouli oil corresponded to 112 targets, and the intersection obtained 97 common targets of patchouli oil for IBD treatment. GO enrichment analysis yielded 53 items. Eighteen items were obtained by KEGG enrichment analysis, involving cAMP signaling pathway, Notch signaling pathway, adhesion connection, Th17 cell differentiation and other signaling pathways. Molecular docking showed that the selected active components of patchouli oil had good binding activity with the targets. Differentially expressed genes were enriched in inflammatory pathways such as Toll-like receptors, JAK-STAT and NF-κB signaling pathways. q-PCR showed that patchouli oil, patchouli alcohol, pogostone can reduce the mRNA levels of cytokines (TNF-α, IL-1β, IL-6, and IL-23) and up-regulate the mRNA levels of tight junction proteins (occludin and claudin-1) in the inflammatory model of NCM460 normal colon epithelial cells. Patchouli alcohol can significantly reduce the levels of TNF-α, IL-6, and IL-1β inflammatory factors in RAW264.7 macrophages induced by LPS. This study revealed the multi-component, multi-target and multi-pathway of patchouli oil, and confirms the anti-inflammatory effect of patchouli oil and its main components in the inflammatory cell model in vitro and the protection of intestinal epithelial barrier integrity function, which provides a theoretical basis for further elucidating the mechanism of patchouli oil in the treatment of IBD.
Compound reserpine and triamterene tablets (CRTT), a compound antihypertensive drug developed by Chinese scientists, is still widely used in clinical practice. However, the mechanisms by which CRTT treats hypertension remain to be fully understood. This study used network pharmacology to analyze CRTT's antihypertensive mechanisms with in vitro experiments. The targets of the four chemical components of CRTT were collected from the Swiss Target Prediction database; 1 828 protein targets related to hypertension were collected from the Therapeutic Target Database (TTD) and Online Mendelian Inheritance in Man (OMIM) database. The CRTT-hypertension network model was constructed using a search tool for recurring instances of neighbouring genes (STRING). Gene ontology (GO) and pathway enrichment analysis of targets of interest was conducted with the Metascape database. In the in vitro study, human umbilical vein endothelial cells (HUVEC) and vascular smooth muscle cells (VSMC) were treated with 1 μmol·L-1 angiotensin Ⅱ (AngⅡ) and CRTT was administered at concentrations of 0.01, 0.1, and 1 μmol·L-1. Changes in the phosphatidylinositol-3-kinase/protein serine threonine kinase/endothelial nitric oxide synthase (PI3K/Akt/eNOS) pathway in HUVEC and the cyclic guanosine monophosphate/cGMP-dependent protein kinase (cGMP/PKG) pathway in VSMC were determined by Western blot. Network pharmacological analysis revealed that the antihypertensive effect of CRTT is closely associated with biological pathways such as vascular tone regulation, adrenergic receptor activation, protein kinase activity and signaling pathways such as the cGMP/PKG signaling pathway, vascular smooth muscle contraction, neuroactive ligand-receptor interaction, adrenergic signaling in cardiomyocytes and calcium signaling pathways. The in vitro study confirmed that CRTT increased the levels of phosphorylated phosphatidylinositol-3-kinase (p-PI3K), phosphorylated protein serine threonine kinase (p-Akt), phosphorylated endothelial nitric oxide synthase (p-eNOS) in HUVEC and the levels of eNOS, phosphorylated vasodilator-stimulated phosphoprotein (p-VASP), and PKG in VSMC through multiple targets and pathways. These results suggest that the activation of PI3K/Akt/eNOS pathway and endothelial-dependent NO/cGMP signaling may be involved in the CRTT-mediated hypotensive effect.
Caveolin-1 (CAV-1) is related to inflammation, oxidative damage, and immunity. In order to obtain a series of dibenzoylmethane halophenols with strong anti-inflammatory and antioxidant effects targeting CAV-1, twenty-nine target compounds were therefore synthesized by Baker-Ventaraman rearrangement and demethylation reaction, starting from the substituted benzoyl chloride and o-hydroxyacetophenone, and their interactions with CAV-1 were investigated by BLI technique. Their in vitro anti-inflammatory and antioxidant properties were also evaluated. The results showed that compounds A6, A17, A18, and A29 not only specifically bind to CAV-1, but also present strong anti-inflammatory and antioxidant effects. These results suggest that this class of compounds can affect the signaling pathways related to inflammation and oxidative stress by directly acting on CAV-1. In particular, these compounds exhibit the most significantly inhibitory effects on IL-1β and COX-2 release. IL-1β plays a key regulatory role in the development of arthritis. Therefore, it is worth expecting for the application of such compounds in the prevention and treatment of arthritis.
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