Twenty-five compounds of novel quinoxaline-based scaffold with antiplatelet activity were designed and synthesized on the basis of previous quinoxaline analogues, and the structures were confirmed by ¹H NMR, ¹³C NMR, and MS. The antiplatelet activity was evaluated, structure-activity relationship (SAR) study was summarized and the selectivity of PAR4 was confirmed by calcium mobilization assays. It was indicated that compound 14a, 14g, 13i, 13p showed moderate activity against PAR4, especially, the activity of compound 14g (IC₅₀ = 0.26 μmol·L^-1) was 6.7 times than the lead compound A (IC₅₀ = 1.73 μmol·L^-1). Therefore, 2, 3-dihydro-[1, 4]dioxino[2, 3-g]quinoxaline and [1, 3]dioxolo[4, 5-g]quinoxaline derivatives are promising compounds for the discovery of novel antiplatelet agents. It is worthy of further research to develop highly effective and selective PAR4 antagonists.

UHPLC-Q-TOF/MS metabonomics technology was used to clarify the metabolic regulation pathways by which Platycodon total saponins (PTS) exert antitussive and expectorant effects in a mouse cough model, in which coughing is induced by concentrated ammonia, and in a phenol red excretion model. After approval by the Experimental Animal Ethics Committee of Jiangxi University of Chinese Medicine (Approval No. JZLLSC-20190235), the mice were randomly divided into a normal group, a model group, a positive drug group and a PTS group. Endogenous metabolites in mouse serum were identified by UHPLC-Q-TOF/MS. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used for multivariate analysis. Metabolic pathways were analyzed by the Metaboanalyst platform. The results show that PTS can significantly prolong the cough latent period and cough frequency of mice, and significantly increase phenol red excretion. UHPLC-Q-TOF/MS identified 19 metabolites related to cough, and PTS significantly decreased 16 of them; 17 metabolites related to expectoration were identified, and PTS decreased the levels of all. Metabolic pathway analysis showed that linoleic acid metabolism, arachidonic acid metabolism and glycerophospholipid metabolism were the main pathways involved in serum metabolite changes in this mouse cough model. Linoleic acid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, arachidonic acid metabolism, phenylalanine metabolism and α-linolenic acid metabolism were the main pathways involved in serum metabolite changes in the phenol red excretion model. This study is the first to elucidate the regulation of antitussive and expectorant metabolic pathways and the effect of PTS on these pathways.

Pulmonary hypertension is a rapidly progressing disease of the lung vasculature with poor prognosis, ultimately leading to right heart failure and death. The remodeling of small pulmonary arteries represents an important pathological characteristic of pulmonary hypertension. Pulmonary arterial smooth muscle cells (PASMCs) located in the middle layer of pulmonary artery exhibit hyperproliferation and resistance to apoptosis, which is the main initiator of pulmonary vascular remodeling and similar to that seen in tumor cells. In this review we focus on the signaling pathways that play a key role in PASMCs proliferation and the latest research progress on inhibitors targeting cell proliferation pathways to provide a new perspective for the treatment of PH.

Mitochondria is involved in many important physiological activities such as energy supply, signal transduction, cell differentiation, etc., and plays an significant role in the occurrence and development of diseases. Using mitochondria as a target is a new strategy for cancer treatment. The use of nanotechnology to construct a mitochondrial targeted nano-drug delivery system can improve the solubility of traditional drugs, prolong the half-life of drugs in the body, increase the bioavailability and concentration of drugs at the tumor site, and reduce the toxic and side effects of drugs. It is expected to solve the resistance in the process of tumor treatment. This review focuses on the field of cancer treatment. Firstly, it introduces the mechanism of mitochondrial targeted nano-drug delivery system for cancer treatment. Secondly, it outlines the design ideas, classification and application research of mitochondrial targeted nano-drug delivery systems in the past five years. Finally, it expands the analysis of other studies that target mitochondria, such as bionic vectors, and presents its advantages and disadvantages, which provide a basis for in-depth research on drug delivery systems in the future.

The crude Et₂O extract of soft coral Sarcophyton glaucum, collected off the Xisha, the South China Sea, were investigated. A new cembrane-type diterpenoid, namely 15-dehydroxy-sarcophytrol D (1), together with twenty-five known compounds, namely ximaoglaucumin C (2), (11S, 12S, 1E, 3E, 7E)-11, 12-epoxycembra-1, 3, 7-triene (3), sarcophytol W (4), cembrene (5), sarcophytol B (6), sarcophytol K (7), sarcophytol J (8), pentaene-cembrene (9), sarcophytol E (10), (+)-marasol (11), (2S)-sarcophytoninsarcophytoxide (12), (-)-17-hydroxydeepoxysarcophytoxide (13), (+)-sarcophytoxide (14), 13-acetoxysarcophytoxide (15), bophynin B (16), 16-oxosarcophytoxide E (17), sarcophinone (18), 7α-8β-dihydroxydeepoxysarcophine (19), (+)-sarcophine (20), 14-dehydroxy-sarcophytol L (21), sarcophytol L (22), 13α-hydroxy-sarcophytol L (23), trocheliophol C (24), trocheliophol E (25) and trocheliophol L (26), were isolated and purified by comprehensive chromatography methods of silica gel column, Sephadex LH-20 gel column, TLC, and semi-preparative high-performance liquid chromatography (HPLC). In anti-inflammatory bioassay, compound 4 exhibited inhibitory effects on lipopolysaccharide (LPS)-induced inflammatory responses in BV-2 microglial cells.

This study identified the exact molecular mechanisms of baicalein on neuroinflammation in lipopolysaccharide (LPS)-induced BV-2 cells. Bioinformatics methods and molecular docking were integrated for predicting the potential targets and mechanisms of baicalein. Immunofluorescence staining and Western blot were used to analyze the predicted key targets [inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2)], the expression level of protein related to signal transducer and activator of transcription 1/nuclear factor kappa-B (STAT1/NF- κB) signaling pathway and its upstream regulator NADPH oxidase-2 (NOX2), and then the mechanism of baicalein in alleviating neuroinflammation was explored. The results showed that iNOS and COX-2 were predicted as the key targets and NF-κB signaling pathway was one of the important pathways by bioinformatics methods and molecular docking. Experimental verification showed that baicalein could significantly reduce the expression of iNOS and COX-2, inhibit the phosphorylation of NF-κB and STAT1 and the production of NOX2 in LPS-induced BV-2 cells. To sum up, baicalein could effectively inhibit the inflammatory reaction in LPS-induced BV-2 cells through regulating NOX2 (gp91^phox/p47^phox)/STAT1/NF-κB pathway.

To establish a quantitative analysis of multi-components by single marker (QAMS) for the determination of Aster souliei Franch., the relative correction factors (f_x) of neochlorogenic acid, cryptochlorogenic acid, rutin, isoquercitrin, isochlorogenic acid B, isochlorogenic acid A, isochlorogenic acid C, quercetin, apigenin and kaempferol were established by ultra-high performance liquid chromatography with chlorogenic acid as internal reference. Meanwhile, the content of each component was determined by the external standard method (ESM) and QAMS, and a linear regression model was established to verify the feasibility and accuracy of the QAMS. Hierarchical clustering analysis (HCA) and orthogonal partial least square discriminate analysis (OPLS-DA) were used to evaluate the quality of 23 batches of A. souliei. The results showed that the repeatability of each f_x was good. The average content of neochlorogenic acid, cryptochlorogenic acid, rutin, isoquercitrin, isochlorogenic acid B, isochlorogenic acid A, isochlorogenic acid C, quercetin, apigenin and kaempferol in 23 batches of A. souliei by QAMS was 0.165, 0.234, 6.115, 0.478, 0.484, 3.359, 1.382, 0.210, 0.172, and 0.057 mg·g^-1, respectively. The mean content determined by the ESM method was 0.163, 0.235, 6.172, 0.479, 0.483, 3.343, 1.413, 0.207, 0.171, and 0.056 mg·g^-1. The results of HCA and OPLS-DA analysis show that 23 batches of A. souliei can be divided into two groups based on caffeic acid content. The content of the first group was between 0.873 to 5.647 mg·g^-1, while the second was between 8.524 to 16.705 mg·g^-1. This QAMS method can be used to simply and quickly evaluate the quality A. souliei.

Molecular mass distribution of Astragalus polysaccharides is wide. Astragalus polysaccharides prepared by conventional water extraction and alcohol precipitation are mostly mixture of macromolecules. Although studies have shown that Astragalus polysaccharides have two-sided immunomodulation, the relationship between anti-inflammatory components and molecular mass distribution of Astragalus polysaccharides is not clear. Therefore, Astragalus polysaccharides were extracted by water extraction and alcohol precipitation. The relative molecular weight of them was determined by high performance gel permeation chromatography (HPGPC). Astragalus polysaccharides with different molecular weights were separated and prepared by membrane separation. RAW 264.7 cells were induced by lipopolysaccharide (LPS) to establish an inflammatory cell model in vitro and the anti-inflammatory polysaccharide were screened. The anti-inflammatory regulation mechanism of Astragalus polysaccharides was analyzed by the LC-MS/MS metabonomics technology. The results showed that APS was composed of APS-Ⅰ (> 2 000 kDa) and APS-Ⅱ (10 kDa). APS-Ⅰ was composed of mannose, rhamnose, galacturonic acid, glucose, galactose, arabinose and the molar ratios of these monosaccharide of APS-Ⅰ were 0.54∶0.26∶12.24∶17.24∶8.46∶1. APS-Ⅱ was composed of rhamnose, galacturonic acid, glucose, galactose, arabinose and the molar ratios of these monosaccharide of APS-Ⅱ were 0.26∶0.14∶24.04∶0.62∶1. APS-Ⅰ and APS-Ⅱ had no cell toxicity to RAW 264.7 macrophage in the range of 0-100 μg·mL^-1. Compared with the model group, APS-Ⅰ at a concentration of 0-100 μg·mL^-1could significantly inhibit the secretion of NO and TNF-α by RAW 264.7, and can significantly promote the secretion of IL-10. APS-Ⅰ had better anti-inflammatory activity than APS-Ⅱ in vitro. The metabolomics results showed that 32 different metabolites were found between the model group and blank group; APS-Ⅰ group can significantly callback 18 different metabolites; mainly related to arginine biosynthesis, arginine and proline metabolism, pyrimidine metabolism, citric acid cycle (TCA cycle), cysteine and methionine acid metabolism, tryptophan metabolism. This study found that APS-Ⅰ had better anti-inflammatory activity than APS-Ⅱ in vitro, and its mechanism may be closely related to amino acid metabolism and energy metabolism, which indicated the direction for further clarifying the pharmacodynamic material basis of Astragalus polysaccharides.

Ionic liquids (ILs) are liquid mixtures formed by anions and cations in a certain stoichiometric ratio under certain conditions. They are widely used in various fields because of their simple preparation process, low volatility, high stability, high conductivity and non-flammability. Here, we firstly introduce their formation principles, classification, and physical and chemical properties in detail. Then, we summarize their functions in pharmaceutical preparations, such as improving the solubility of insoluble drugs, enhancing the stability of drugs, and promoting the permeability of drugs, as well as their role as active pharmaceutical ingredients (API) to fabricate new drug delivery systems of API-ILs. Finally, we reviewed the applications of ILs in different administration routes, including oral, transdermal, mucosal, and injection routes, and meanwhile offer perspectives for the further use of ILs.

In this paper, the low-field nuclear magnetic resonance technology CPMG (Carr-Purcell-Meiboom-Gill) echo method was used to determine the cross-linking degree and cross-linking density of crospovidone (PVPP) from different manufacturers. Based on the seven physical properties of PVPP, a fingerprint spectrum (radar chart) of twenty secondary quality indicators were obtained, and three compressibility evaluation indicators, index of the parameter (IP), index of parametric profile (IPP), index of good compression (IGC) were calculated by the fingerprint spectrum. It was found that the cross-linking degree and compressibility index IP of PVPP showed a strong correlation (r=0.816) by the correlation analysis, indicating that the cross-linking degree is one of the key quality attributes for evaluating the compressibility of PVPP.