Huang-Qin is a traditional Chinese medicine with antiviral, antioxidant, and anti-inflammatory activities. Its major bioactive compounds are diverse flavone O-glucuronides and glucosides. Although three flavonoid O-glycosyltransferases have been identified from S. baicalensis, this information is not sufficient to elucidate the structural diversity of flavonoid glycosides. In this study, nine glycosyltransferase candidate genes were discovered from S. baicalensis by BLAST analysis and their functions were characterized after heterologous expression. Three new flavone O-glycosyltransferases were able to catalyze the formation of major compounds in S. baicalensis, including baicalin and wogonoside. These enzymes could also utilize exogenous flavones as sugar acceptors. This work further elucidates biosynthetic pathways for Scutellaria flavonoid O-glycosides.

To explore the effect of tanshinone IIA (TanIIA) on the occurrence and development of breast cancer, we employed the mouse mammary tumor virus-polyomavirus middle T antigen (MMTV-PyMT) transgenic mice as a spontaneous breast cancer mouse model. Animal welfare and experimental procedures were in accordance with the regulations of the Animal Ethics Committee of Nanjing University of Chinese Medicine. The animals were divided into control group, low-dose TanIIA treatment group (30 mg·kg^-1·day^-1), and high-dose TanIIA treatment group (60 mg·kg^-1·day^-1). The treatment was administered orally and daily for 5 weeks. The mice were sacrificed after final treatment. Mammary gland and lung were collected for histopathology studies. We evaluated the chemoprophylaxis effect of TanIIA on breast cancer in mice according to the pathological characteristics of breast cancer at different stages of development. Immunofluorescence staining were employed for blood vessel analysis. The expression levels of E-cadherin, proliferating nuclear antigen (PCNA), and oncogene c-Myc were detected by immunohistochemistry. Flow cytometry was used to analyze cell cycle and Cytoscape was used to construct drug-disease protein-protein interaction (PPI) network. Our results showed that TanIIA inhibits breast tumor progression by delaying malignancy from adenoma to early carcinoma, and inhibits blood vessel formation during tumor development. TanIIA (60 mg·kg^-1·day^-1) inhibits the expression levels of PCNA and c-Myc, upregulates the expression of E-cadherin. In addition, cell cycle experiments showed that the cell cycle of PyMT primary mammary cells in the high-dose TanIIA group was arrested in the G0/G1 phase. Our study demonstrated that TanIIA can significantly inhibit breast tumor progression in MMTV-PyMT mouse model, which may be related to the inhibition of angiogenic switch and cell cycle arrest.

ZSP1601, a novel pan-phosphodiesterase inhibitor is in development for the treatment of nonalcoholic steatohepatitis. A physiologically-based pharmacokinetic (PBPK) model was developed to predict the pharmacokinetics of ZSP1601 in human. The PBPK model following intravenous and oral dose of ZSP1601 in rats and dogs was firstly built using preclinical in vitro and in vivo data. The PBPK model in human was then built based on models in animal. The in vitro-in vivo extrapolation (IVIVE) method and some allometric scaling methods were used to predict the clearance in human, respectively. The PBPK models using IVIVE and allometry of unbound CL plus the rule of exponents methods predicted the pharmacokinetics of ZSP1601 in healthy Chinese subjects successfully. The predicted parameters C_max and AUC following single oral dose administration were within 0.5-2 folds of the observed data. The model was optimized and the final model was used to predict the pharmacokinetics of ZSP1601 in North European Caucasian, Geriatrics, Obese and Morbidly Obese, respectively. Animal studies were approved by the Animal Management and Use Committee of Suzhou AppTec Inc., and the approved No. is SZ20140916.

A simple and efficient method for extracting Cistanche polysaccharides was obtained and used to extract four Cistanche polysaccharides. The molecular weight, distribution and polysaccharide mass fraction of the four Cistanche polysaccharides were measured by High performance size exclusion chromatography-multiangle laser light scatter-refractive index detector (HPSEC-MALLS-RID) and differences between the four Cistanche polysaccharides were determined. The results of a single factor test and an orthogonal test showed that the best process parameters for extracting Cistanche polysaccharides used a mixture of enzyme (4%), a ratio of complex enzyme (cellulase∶pectinase) 1∶1, ultrasonic power at 350 W (40 kHz), for 20 min, enzymolysis temperature of 50 ℃, and pH 6. The average yield of three repeated extractions was 5.14%, the mass fraction was 90.78%, the comprehensive index was 47.96%, and the RSD = 1.51%, indicating good reproducibility. The four Bossica Cistanche polysaccharides are all spherical structures but their molecular weights and distributions differ. The optimized compounded enzyme combined with ultrasonic extraction increases the yield of Cistanche polysaccharides. It is a simple, convenient, economical and environmentally friendly extraction method, which lays the foundation for future polysaccharide research.

Hesperidin nanosuspensions (HDN-NS) were prepared with tea saponin (TS) as stabilizer. The feasibility of TS as a natural stabilizer and the mechanism of TS stabilized nanosuspensions were investigated to provide reference for the development of green nano-preparations of hesperidin. HDN-NS was prepared by high-speed shearing combined with high-pressure homogenization. Using average particle size and polydispersity index as evaluation indexes, the effects of drug concentration, shearing speed, shearing time, homogeneous pressure and homogeneous cycles on HDN-NS were investigated by single factor experiment. The results of single factor investigation were as follows: drug concentration was 8.0 mg·mL^-1, shearing speed was 16 000 r·min^-1, shearing time was 2 min, the homogeneous cycles were 6 cycles at 35 MPa and 12 cycles at 100 MPa. The pH, ionic strength, zeta potential and critical micelle concentration of TS were investigated to determine the role of electrostatic repulsion in the mechanism of TS stabilized nanosuspensions. The results showed that electrostatic repulsion is involved in the mechanism of TS stabilized HDN-NS. In conclusion, at low concentration, TS can significantly reduce the particle size of HDN-NS, which indicates that TS has the potential to stabilize nanosuspension. Electrostatic repulsion is one of the mechanisms of TS stabilizing nanosuspension.

The study was undertaken to clarify the differences in metabolite groups between Aster yunnanensis and Pulicaria insignis to establish plant origin and identify plant resources. Non-target metabolomics of A. yunnanensis and P. insignis was undertaken with sample derivatives and gas chromatography-mass spectrometry (GC-MS). Principal component analysis (PCA), partial least-squares discriminant analysis (PLS-DA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were used to characterize the differing metabolites of A. yunnanensis and P. insignis. Correlation analysis of these metabolites and metabolic pathway analysis allowed us to identify metabolic pathway changes between samples. Characterization of the antibacterial activity of the essential oil from A. yunnanensis and P. insignis showed that 384 metabolites were identified in the two species, including amino acids and peptides, phenylpropanoids, aromatics, glycoside, nucleotide, flavonoid, alkaloids, saccharides, vitamin, organic acid, lipids, esters, alcohol. A total of 92 differential metabolites with significant differences in content (P < 0.05, VIP > 1) were identified. In conclusion, a new method based on pre-column derivatives and GC-MS metabolomics was used to distinguish and compare A. yunnanensis and P. insignis metabolites.

In this study, 9 aztreonam prodrug compounds were designed and synthesized, and their metabolic stability in plasmas of different species (rat, mouse, dog, monkey and human) were evaluated. Species differences were observed in aztreonam carboxylates's sensitivity to the plasma esterases among different species, and the hydrolysis rates of aztreonam carboxylates in rodent plasmas were much higher than in non-rodent plasmas. Moreover, the hydrolysis rates of aztreonam carboxylates might be positively correlated with the ClogP values in human plasma. These results provide useful guidance for the further development of monocyclic β lactam prodrugs.

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.

Idiopathic pulmonary fibrosis (IPF) is an irreversible and highly mortal interstitial disease. The incidence of IPF is increasing around the world, which seriously harms human health and brings huge economic burden to the society. While traditional treatments can slow the progression of the disease, they are far to cure this disease. Clinically, pirfenidone and nintedanib are two main drugs that used for the treatment of IPF. However, severe adverse reactions were reported in some patients. Therefore, it is very important to explore novel therapeutic strategies to reverse fibrosis and regenerate lung. The repair and regeneration ability of stem cells has unique advantages in the treatment of pulmonary fibrosis. The structure and function of organoids produced by stem cells have similar characteristics with live organs. Therefore, lung stem cells play an important role in the discovery of novel anti-IPF drugs, and in the formation and development of lung tissue. In addition, organoids produced by stem cells also serve as a perfect model for regenerative medicine. In this review, we mainly summarize the role of stem cells and organoids in the repair and regeneration of pulmonary fibrosis, and hope to provide a reference for the development of clinical treatment of pulmonary fibrosis.