To establish a quality evaluation method for Astragali Radix using polysaccharide as quality control index, we established the Astragalus polysaccharide and monosaccharide sugar spectra, and combined with immunological activity test. High performance liquid chromatography (HPLC) was used to establish the specific chromatograms of Astragalus polysaccharides and monosaccharides. The data were analyzed by multivariate statistical analysis and cluster analysis using SIMCA software and SPSS software to distinguish Astragalus membranaceus var. mongholicus from different habitats or planting methods. The activity was evaluated by testing mouse peritoneal macrophage phagocytosis using neutral red. The results showed that the content of polysaccharides and the ability of enhancing phagocytic activity of macrophages from imitation wild Astragali Radix in Shanxi Hunyuan was higher than cultured Astragali Radix. The polysaccharides of Astragali Radix from Shanxi Hunyuan, Shanxi Wuzhai and Gansu Longxi have similar molecular weight distribution, but the peak area of each part has a significant difference in the percentage of the total peak area. The part of the polysaccharide of Shanxi Astragalus membranaceus with a molecular weight of about 10 kDa is higher than that of Gansu. Principal component analysis (PCA) shows that Astragali Radix from Shanxi and Gansu can be separated. All three are composed of five monosaccharides such as rhamnose, glucose, galactose, arabinose and galacturonic acid. However, the Astragalus polysaccharides (APS) in the three regions have different ratios of monosaccharide substances. The PCA display can distinguish three different Astragalus membranaceus var. mongholicus. This study used a combination of fingerprint of carbohydrates and the effects of APS on cellular immune function to provide a basis for quality evaluation and quality control of different habitats or planting methods.

Alzheimer's disease (AD) is a neurodegenerative disease that seriously threatens the life of the elderly and there is no effective therapy to treat or delay the onset of this disease. Due to the multifactorial etiology of this disease, the multi-target-directed ligand (MTDL) approach is an innovative and promising method in search for new drugs against AD. In order to find potential multi-target anti-AD drugs through reposition of current drugs, the database of global drugs on market were mined by an anti-AD multi-target prediction platform established in our laboratory. As a result, inositol nicotinate, cyproheptadine, curcumin, rosiglitazone, demecarium, oxybenzone, agomelatine, codeine, imipramine, dyclonine, melatonin, perospirone, and bufexamac were predicted to act on at least one anti-AD drug target yet act against AD through various mechanisms. The compound-target network was built using the Cytoscape. The prediction was validated by molecular docking between agomelatine and its multiple targets, including ADORA2A, ACHE, BACE1, PTGS2, MAOB, SIGMAR1 and ESR1. Agomelatine was shown to be able to act on all the targets above. In conclusion, the potential drugs for anti-AD therapy in the database for global drugs on market was partially uncovered using machine learning, network pharmacology, and molecular docking methods. This study provides important information for drug reposition in anti-AD therapy.

Microspheres based on polylactic acid-glycolic acid (PLGA) copolymer have unique advantages in pulmonary controlled drug delivery. However, the clearance mechanism dominated by lung macrophage phagocytosis greatly limits the long-term retention of drugs in the deep lung. In order to avoid the scavenging effect of lung macrophages, the PLGA microspheres coated by polyethylene glycol-distearoyl-glycero-phosphoethanolamine (PEG-DSPE) was designed in this study, and the effect of chain length of PEG-DSPE and its ratio on the macrophage uptake was investigated. With coumarin 6 as a fluorescent probe, the coumarin 6-loaded PLGA microspheres was prepared by premix membrane emulsification/solvent evaporation. The particle size was controlled to 3-5 μm and the encapsulation efficiency was over 90%. After incubation in the cell culture fluid for 48 h, the in vitro leakage of fluorescein from the microspheres was less than 1.5%, eliminating the interference of free fluorescein on the cellular uptake. Murine macrophages RAW264.7 cell line was selected for the in vitro cell study. The preparations showed little toxicity to cells in the cytotoxicity study. Results of the macrophage uptake study showed that PEG₅₀₀₀-DSPE and PEG₁₀₀₀₀-DSPE coated groups with both high and low proportions (PEG-DSPE/PLGA 1:1, 0.25:1) could significantly reduce the phagocytosis of macrophages to microspheres compared with the uncoated PLGA group. For PEG₂₀₀₀-DSPE coated microspheres, the effect of escaping macrophage phagocytosis could be achieved by increasing the ratio of polyethylene glycol (PEG) on the surface of particles. Overall, the chain length of PEG-DSPE and its ratio are the key factors affecting the macrophage uptake. In pulmonary controlled drug delivery, high molecular weight of PEG-DSPE (PEG₅₀₀₀-DSPE and PEG₁₀₀₀₀-DSPE) and the high ratio (PEG-DSPE/PLGA 1:1) of PEG₂₀₀₀-DSPE can be selected to escape the phagocytosis of alveolar macrophages and prolong the drug retention in the lungs.

Flavonoids are important active ingredients in traditional Chinese medicine. However, their applications for the pharmaceutical use are greatly limited by low oral bioavailability due to poor aqueous solubility. The study of pharmaceutical crystallography is a potential approach to solve many problems of poor solubility. Research progress of flavonoid compounds in pharmaceutical crystallography field was reviewed from following aspects:polymorphism, cocrystal, amorphous/co-amorphous and nanocrystals. The information provided here is expected to serve as a reference for the applications of pharmaceutical crystallography in the poorly soluble components of traditional Chinese medicine.

In this study, we accurately collected the embryonic parenchyma cells and endocarp stone cells of Arctii Fructus at five different growth stages by laser microdissection. Quantitative analyse of caffeic acid, arctiin and arctigenin in these cells were performed using ultra-fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS). The results showed that a large amount of arctiin was produced and accumulated in embryonic parenchyma cells from the late flowering stage to mature stage, while much lower content of arctiin was produced and accumulated in endocarp stone cells at these stages. It suggested that the biosynthetic pathways of arctiin were different in embryonic parenchyma cells from endocarp stone cells of Arctii Fructus. Arctigenin was found to be produced and accumulated in both embryonic parenchyma cells and in endocarp stone cells from the late flowering stage to mature stage, but it reached a peak in endocarp stone cells at late flowering stage, then decreased slowly. The concentration of arctigenin was far less than that of arctiin regardless of embryonic parenchyma cells or endocarp stone cells. These results have validated the new method for analysis of dynamic accumulation of arctiin in Arctii Fructus by UFLC-MS/MS with frozen sections and microdissection.

Elabelas/Toddlers belong to a group of endogenous active peptides recently discovered from zebrafish. The sequences of these peptides have 25% homology to Apelin. These peptides regulate physiological functions of organisms through putative protein receptors related to the angiotensin receptor AT1 (APJ). Functional roles of Elabela include early embryonic development, angiogenesis, fluid homeostasis, and feeding or dietary behavior control. Elabela also participates in the development of many diseases, such as heart failure, preeclampsia, acute kidney injury, hypertension, and diabetes. Increasingly, studies have shown that Elabela/APJ signaling can promote normal development of early embryos, including differentiation of mesoderm and endoderm, and formation of cardiac morphology and function. At the same time, the signaling can also promote angiogenesis or migration and proliferation of tumor cells. Here we describe the molecular structure, biological characteristics, functions and application prospects of Elabela/APJ signaling.

To ensure the consistency of quality in recombinant protein production, the cell bank for biologics should be derived from a single clone. A number of techniques have been used for cloning and assurance from the cellular pool after transfection with a target gene. Here, using CHO cell as an example, we summarize the knowledge and understanding of monoclonality of production cell bank from both industries and regulatory authorities, and propose general considerations on the requirements of monoclonality for clinical trial application and new drug application based on current techniques. Furthermore, we suggest quality control strategies and assessment methods for those cell banks from non-single clones.

CY-1-4 is a tryptanthrin derivative exhibiting antitumor activity. The solubility of CY-1-4 was poor and the corresponding mechanism needs further study. To solve this problem, we prepared nanoparticles encapsulated with CY-1-4 (CY-1-4 NPs) by nanoprecipitation method using poly(caprolactone) (PCL) and poly(ethylene glycol)-co-poly(ε-caprolactone) (PEG-PCL) as carriers to improve solubility. We then explored whether CY-1-4 NPs induced B16-F10 cytotoxicity via ferroptosis by determining the effect of CY-1-4 NPs on reactive oxygen (ROS) levels, repairing efficacy of lipid reactive oxygen inhibitor ferrostatin-1 and iron chelator deferoxamine (DFO), and potentiation of protoporphyrin (PPIX) induced B16-F10 cell death. The results showed that nanoparticlated strategy significantly improved solubility of CY-1-4. With the particle size about 116 nm, encapsulating efficacy was about 83% and the drug loading capacity was about 4.80%. Ferroptosis mechanistic studies indicated that CY-1-4 NPs could improve the ROS level in B16-F10 cells, whereas ferrostatin-1 and DFO could partly inhibited the cytotoxicity and PPIX could potentiated the cytotoxicity of CY-1-4 NPs in B16-F10 cells. These results showed that ferroptosis was one of the cell death mechanisms induced by tryptanthrin derivative CY-1-4 nanoparticle.

The chemical constituents of Viburnum taitoense Hayata were investigated using column chromatography silica gel and Sephadex LH-20, etc. Seven pentacyclic triterpenoids were isolated and their structures were elucidated by spectral data and physicochemical properties as 3β, 6β-dihydroxy olean-11, 13(18)-dien-28-acid (1), 3β-hydroxy olean-11, 13(18)-diene-28-acid (2), 12-ene-olean-28-acid-3β-palmitate (3), 3β-acetylcocodiol (4), corosolic acid (5), uvaol (6) and ursolic acid (7). Among them, compound 1 is a new oleanane type triterpenoid and its absolute configuration was confirmed by single-crystal X-ray diffraction data. Compounds 2-5 were isolated from this genus for the first time. All the compounds were evaluated for their anti-inflammatory activities in vitro, and compound 5 showed significant inhibitory activity against nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW264.7 macrophage cells with an IC₅₀ of 25.52 ±0.56 μmol·L^-1 when compared to the positive control, quercetin (IC₅₀ of 25.46 ±0.62 μmol·L^-1).

This study was designed to compare intestinal bacteria and inflammatory cytokine expression in rats with ulcerative colitis (UC) after treatment of three regiments, Huang-qin-tang (HQT), Si-shen-wan (SSW), and Tong-xie-yao-fang (TXYF). After approved by Institute of Chinese Materia Medica Ethics Committees in China Academy of Chinese Medical Sciences, UC in rats was induced by using a compound method (trinitrobenzenesulfonic acid plus ethanol). Rats were randomly divided into control, disease, positive control salazosulfapyridine (SASP, 0.5 g·kg^-1), HQT (20 g·kg^-1), SSW (26 g·kg^-1), and TXYF groups (22 g·kg^-1). After 7 days of treatment, colonic tissues and the blood were taken for various assays. Damage of colonic tissues was detected by H & E staining. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8) and prostaglandin E₂ (PGE₂) in the serum were detected by the enzyme linked immunosorbent assay (ELISA). Total DNA was extracted from stool samples for analyses of 16SMiseqPE300V3-4 segment using high-throughput sequencing. The inflammatory cytokine results showed that compared with the disease group, the content of IL-6, PGE₂, TNF-α in SASP group were decreased (P < 0.05), with the most significant decrease being the level of IL-8 (P < 0.01), whereas the levels of IL-6, IL-8 and TNF-α in HQT group were reduced (P < 0.05) and PGE₂ content was clearly reduced (P < 0.01). The contents of four cytokines in SSW group were decreased, but there was no statistical difference. While the levels of IL-6 and TNF-α in TXYF group were reduced, and the reductions of IL-8 and PGE₂ were significant (P < 0.05). The results after sequencing showed that microbiome species richness SSW group > HQT group > TXYF group; the similarity between samples TXYF group > SSW group > HQT group; the species of HQT and TXYF group have greater difference when compared to the disease group. The content of beneficial bacteria in the intestine of HQT group > SSW group > TXYF group. Three regiments all have therapeutic effects on UC, manifested by improvements of the signs and mental status of UC rats. However, in terms of inhibition of inflammatory factors IL-6, IL-8, PGE₂ and TNF-α, and regulation of intestinal microbiome, the therapeutic effect of HQT was superior than SSW and TXYF.