The mechanism of Platycodon grandiflorum in the treatment of pulmonary fibrosis was examined by integrated pharmacology network with animal experiment validation. Compositions and targets of Platycodon grandiflorum were collected utilizing databases such as TCMSP and Swiss Target Prediction, whereas pulmonary fibrosis targets were obtained using GeneCards, OMIM, Disgenet, and Drugbank databases. These datasets were merged in order to identify prospective Platycodon grandiflorum targets for the treatment of pulmonary fibrosis. The "drug-component-target-disease" network was constructed with Cytoscape software, and the interaction relationship between potential targets was produced; they were coupled with the String platform to create the PPI network while also doing topological analysis. Then, using R software and the Bioconductor biological information software package, we conduct GO and KEGG enrichment analysis to estimate the therapeutic mechanism. A mouse model of pulmonary fibrosis was constructed for pathological staining, ELISA, lung function, qRT-PCR, and Western blot to validate the results of the network pharmacology. There are 289 putative active components of Platycodon grandiflorum, and 1 129 disease targets for pulmonary fibrosis, for a total of 65 drug-compound-disease common targets. The GO enrichment analysis revealed 1 575 items, whereas the KEGG enrichment analysis yielded 146 entries. The phosphatidylinositol 3 kinase-protein kinase B (PI3K-AKT) signaling pathway, the tumor necrosis factor (TNF) signaling system, and the interleukin-17 (IL-17) signaling pathway were enriched. In animal experiments, Platycodon grandiflorum was found to decrease lung inflammation and collagen deposition in mice with pulmonary fibrosis. According to Western blot results, the expression of PI3K-AKT signaling pathway-related proteins p-PI3K and p-AKT was down-regulated in a dose-dependent manner after Platycodon grandiflorum therapy of pulmonary fibrosis mice. When p-AKT was suppressed, P21 expression was reduced, indicating that Platycodon grandiflorum may control the expression of PI3K-AKT pathway-related proteins to alter cell senescence while treating mice with pulmonary fibrosis. This study uses network pharmacology to identify the targets and pathways of Platycodon grandiflorum against pulmonary fibrosis and conducts related animal experimental validation, providing a foundation for an in-depth discussion of the therapeutic mechanism of Platycodon grandiflorum against pulmonary fibrosis.

Chaihu Shugan San (CHSGS), a classic traditional Chinese medicinal formula, has been widely used in clinics for emotional disease. Here the protective effect and possible mechanisms of Chaihu Shugan San in stress-induced liver injury were investigated. The animal experimental protocol has been reviewed and approved by Laboratory Animal Ethics Committee of Jinan University, in compliance with the Institutional Animal Care Guidelines. Mice were administered CHSGS for 7 days and subjected to 18-h acute stress before being killed. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and malondialdehyde (MDA) levels in serum were measured with commercial kits. Histomorphology of the liver was analyzed by hematoxylin-eosin staining and immunohistochemistry. Glutathione (GSH) content, 4-hydroxynonenal (4-HNE), brain and muscle Arnt-like protein-1 (BMAL1) and arachidonate 15-lipoxygenase (ALOX15) protein were detected by LC-MS and Western blot, respectively. The results showed that CHSGS ameliorated acute stress-induced liver damage by reducing ALT and AST levels in serum and inflammatory infiltration in liver tissue. Network pharmacology analysis showed that CHSGS was associated with lipid peroxidation. Further analysis confirmed that MDA and 4-HNE levels declined and GSH level increased in livers of stressed mice after CHSGS administration. CHSGS also lowered BMAL1 expression, a pivotal factor in circadian rhythm, in livers of stressed mice. In conclusion, CHSGS ameliorated stress-induced liver injury by repressing lipid peroxidation and regulating circadian rhythm. Our studies implicate that CHSGS is promising as a therapy for stress-induced liver injury, and lay foundation for designing novel prophylactic and therapeutic strategies for stress-induced liver injury.

In this study, we investigated the effect and mechanism of glaucocalyxin A on transforming growth factor-β1 (TGF-β1)-induced differentiation of lung fibroblasts by Western blotting, cellular immunofluorescence and collagen gel contraction assays. We monitored the phosphorylation of Smad3, measured extracellular regulated protein kinases (ERK) 1/2 and glycogen synthase kinse3β (Ser9) activity and the level of β-catenin to elucidate the role of glaucocalyxin A. The results show that glaucocalyxin A significantly decreased the expression of α-smooth muscle actin in lung fibroblasts; glaucocalyxin A remarkably reduced the formation of filaments and collagen gel contraction of lung fibroblasts; glaucocalyxin A notably down-regulated the production of fibronectin; glaucocalyxin A did not affect the phosphorylation level of Smad3 and ERK1/2; glaucocalyxin A markedly inhibited the phosphorylation of GSK3β (Ser9) and the levels of β-catenin; a GSK3β (S9A) mutant significantly inhibited lung fibroblast differentiation; and SKL2001, a β-catenin activator, partly reversed the inhibition of lung fibroblast differentiation by glaucocalyxin A. These results suggest that glaucocalyxin A significantly inhibits the differentiation of lung fibroblasts, which is related to the down-regulation of GSK3β/β-catenin signaling.

Clearance reflects the speed of extraction and elimination of drug molecules from systemic circulation. Reducing the clearance of compounds using structure modification strategy could lead to good pharmacokinetic and pharmacodynamic properties. Herein, the concept of clearance, as well as several prediction methods of in vivo clearance are introduced. The strategies of reducing drug clearance are reviewed. These methods include reducing hepatic metabolic clearance through reducing lipophilicity, blocking metabolic site, scaffold modification and increasing steric hindrance; reducing biliary or renal excretion clearance through increasing lipophilicity, reducing polar surface area and bioisosterism. In addition, the influence of spatial configuration on drug clearance is also summarized.

This article intended to build a component-target network to screen the effective components of Compound Suanzaoren Decoction, and to establish an efficient and rapid method for the determination of effective components. 103 compounds in the Compound Suanzaoren Decoction were identified by HPLC-Q-TOF MS/MS. 27 potential effective substances were analyzed by network pharmacology. The first six components with the largest degree were selected as effective components, including neomangiferin, mangiferin, ferulic acid, senkyunolide Ⅰ, spinosin, and 6'''-feruloylspinosin. A UHPLC method was established for determination. The chromatographic separation was performed on a Waters CORTECS T3 column (2.1 mm×150 mm, 1.6 μm) with the mobile phase of 0.1% phosphoric acid solution and acetonitrile. The results showed that the specificity was good with no interference for the chromatographic peaks. The linear was excellent within the scope of investigation, with the values of r higher than 0.999 0 for all analytes. The method had been verified to have good sensitivity, precision, accuracy, durability and stability. Therefore, the results showed that the method established was suitable for the screening and determination of effective components in Compound Suanzaoren Decoction, which provided a basis for the quality evaluation of traditional Chinese medicine.

Glycosylation abnormalities are common in all stages of tumor development, and sialic acid (SA) modified polysaccharides have been found highly expressed on many different types of tumor cells. These highly sialylated tumor cells promote the formation of tumor immunosuppressive environment and help tumor cells gain metastatic potential by interacting with SA binding receptors Siglecs/selectins expressed on peripheral immune cells or endothelial cells. Related theoretical studies have promoted the development of tumor therapeutic strategies by targeting SA-binding receptors, mainly including specific antibodies trastuzumab (Mylotarg) or polysaccharides that block the interaction between Siglecs/selectins and its ligands, as well as nano-based drug delivery systems modified with SA and its derivatives. This article reviews the specific mechanisms of how SA-binding receptor Siglecs/selectins-mediated interactions contribute to tumor development and metastasis, and tumor therapeutic strategies by targeting SA-binding receptors, as well as makes a rational evaluation and reflection on these therapeutic strategies.

Polymeric micelles have become a potential drug carrier. However, some single-copolymer micelles often have some performance defects, such as low drug loading, poor stability and weak response to microenvironment. Mixed micelles self-assembled from two or more dissimilar macromolecular polymers provides a direct and convenient approach to improve drug delivery. This paper attempts to review the internal force, preparation and characterization, performance advantages and biological activity of mixed polymer micelles, aims to show the advantages of polymer mixed micelles, analyzes the problems and shortcomings, and hopes to provide reference for the development of anti-tumor nano-micelles.

To provide new ideas for further research and treatment of nonalcoholic fatty liver fibrosis, we used bioinformatics technology to search the gene microarray data related to this disease and identified differentially expressed genes and potential therapeutic drugs. Gene Expression Omnibus (GEO) was used to search the entry of "nonalcoholic fatty liver fibrosis"; the GSE109345 microarray data was downloaded, the differentially expressed genes in the control group and the fibrosis model group were screened with the BioJupie analysis platform, and GO function, KEGG pathway, protein-protein interaction (PPI) network analysis and visualization were conducted for the differentially expressed genes. Finally, through the Connectivity Map (CMap) data platform, compounds with potential efficacy on nonalcoholic fatty liver fibrosis were predicted. A total of 109 differentially expressed genes were screened, including 70 up-regulated genes and 39 down-regulated genes. Functional analysis showed that differentially expressed genes were mainly involved in protein kinase B signal transduction, extracellular domain function, small molecule binding and other functions; pathway analysis showed that these genes participated in retinol metabolism, steroid hormone synthesis, and arachidonic acid metabolism; PPI network analysis showed that metallopeptidase inhibitor 1 (TIMP1), chemokine (C-C motif) ligand 2 (CCL2), recombinant signal regulatory protein beta 1 (SIRPB1), and cytochrome P450 (CYP) were the main genes related to nonalcoholic fatty liver fibrosis. CMap analysis showed that pioglitazone, midodrine, arecoline and other compounds had potential efficacy in nonalcoholic fatty liver fibrosis. Thus, by screening for differentially expressed genes, related genes and potential therapeutic compounds effective in the treatment of non-alcoholic fatty liver fibrosis can be identified, as well as new ideas and approaches for the clinical treatment of non-alcoholic fatty liver fibrosis.

Fibrosis is a common manifestation of organ damage and failure. According to relevant statistics in the United States, deaths caused by fibrotic diseases account for 45% of all deaths in the country. Therefore, fibrotic diseases have received widespread attention worldwide. As a key kinase that regulates energy balance, AMP-activated protein kinase (AMPK), which mainly controls the transformation of cells from anabolic to catabolism, and restores the energy balance by phosphorylating its substrates. Therefore, it has become the core of treatment for diabetes and other metabolic-related diseases. Numerous recent pathological studies have shown that the expression of AMPK in fibrotic tissues is significantly down-regulated compared with normal tissues, and activation of AMPK could improve various fibrotic pathological processes (including autophagy dysfunction, oxidative stress, fibroblast proliferation, epithelial-mesenchymal transition, fibroblast-to-myofibroblast differentiation). Therefore, this review will discuss the structure and function of AMPK and its role in important phenotypes of fibrotic diseases, and provide evidence for AMPK as an important target for prevention and treatment of fibrosis.

We analyzed the main chemical constituents of Huangqi decoction by HPLC coupled with diode array and evaporative light scattering detectors (HPLC-DAD-ELSD). The study on the mechanism of Huangqi decoction was based on network pharmacology and included multi-components, multi-targets, and multi-pathways in the treatment of non-alcoholic fatty liver disease (NAFLD). The chemical "fingerprints" of 15 batches of Huangqi decoction were established. Network pharmacology was used to screen and analyze the targets and pathways of the components of Huangqi decoction, and a "component-target-pathway" network was constructed to predict the mechanism of Huangqi decoction for the treatment of NAFLD. HPLC analysis of Huangqi decoction revealed 27 common peaks and the main chemical constituents were identified. Gene ontology (GO) analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis revealed that glycyrrhetinic acid, isoliquiritigenin, glycyrrhizic acid, astragaloside Ⅳ, liquiritigenin, and astragaloside Ⅰ, the main active components of Huangqi decoction, may act on RAC-alpha serine/threonine-protein kinase (AKT1), interleukin-6 (IL-6), vascular endothelial cell growth factor A (VEGFA), mitogen-activated protein kinase 8 (MAPK8), and signal transducer and activator of transcription 3 (STAT3), and may regulate pathways involving phosphatidylinositol-3-kinases (PI3K)/protein kinase B (AKT), insulin resistance, hypoxia inducible factor-1 (HIF-1), tumor necrosis factor (TNF), among others. A decrease in insulin resistance, a reduction of inflammation, and anti-oxidative stress-related effects may be the mechanism of Huangqi decoction for the treatment of NAFLD.