To expand the structural diversity of Matijin-Su (MTS) derivatives and explore novel anti-HBV activity compounds, a series of fluorinated dipeptidomimetics of MTS were designed and synthesized by using trifluoromethyl substituted methylamine unit as bioisostere to replace the amide bond of the MTS derivatives. The structures of all target compounds were confirmed by ¹H NMR, ¹³C NMR, ¹⁹F NMR, HRMS, or ESI-MS, and the crystal structure of 10' was determined by X-ray single crystal diffraction. Their inhibitory activity against hepatitis B virus (HBV) in vitro were evaluated using HepG2 2.2.15 cell model. The results showed that all target compounds had inhibitory effect on HBV DNA replication, the IC₅₀ of 14e, 14f, and 14k were 0.37, 0.29, and 0.79 μmol·L^-1, respectively.

In order to study the chemical composition of Osmanthus fragrans var. thunbergii, the chemical constituents of the dried flower of O. fragrans var. thunbergii were studied. From the 95% ethanol extract of the dried flower, a new monoterpene (1), along with seven known monoterpenes, sesquiterpenes and phenethyl alcohols (2-8), was isolated and purified by silica gel, polyamide, and preparative reversed-phase HPLC chromatography methods. Their structures were identified by 1D-NMR (¹H NMR, ¹³C NMR, DEPT), 2D-NMR (HSQC, HMBC, ¹H-¹H COSY, NOESY), HR-ESI-MS, IR, UV, and its physical and chemical properties as: methyl (R, E)-2-(5-ethylidene-2-oxotetrahydro-2H-pyran-4-yl) acrylate (1), (R, E)-2, 6-dimethyloct-3, 7-dien-2, 6-diol (2), (6R)-2, 6-dimethyloct-7-en-2, 3, 6-triol (3), 2, 4, 4-trimethyl-3-(3-oxobutyl)-cyclohex-2-en-1-one (4), (S)-2, 4, 4-trimethyl-3-(3-hydroxybutyl)-cyclohex-2-en-1-one (5), (R, E)-2, 4, 4-trimethyl-3-(3-hydroxybut-1-en-1-yl)-cyclohex-2-en-1-one (6), (S, E)-3, 5, 5-trimethyl-4-hydroxy-4-(3-oxobut-1-en-1-yl)-cyclohex-2-en-1-one (7), and 2-p-acetoxyphenylethanol (8). 1 is a new compound, 2-8 were isolated from the plant of Osmanthus fragrans var. thunbergii for the first time.

Electrospray ionization (ESI) is easy to be affected by the biological matrix interferences, and thus the accuracy, precision, and reproducibility of the quantitation are significantly impaired. Probe electrospray ionization (PESI) is one of the most typical ambient ionization, which can ionize molecules without complicated sample preparation at the atmospheric environment, and is superior in simplicity, high efficiency, and high throughput. The micro pen electrospray ionization tandem mass spectrometry (μPen-ESI-MS/MS) method was newly developed based on PESI. In this study, the matrix effect of the μPen-ESI-MS/MS method for drug quantitation in plasma samples was evaluated and compared with the liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) method. The μPen-ESI-MS/MS and LC-ESI-MS/MS methods for quantitation of five drugs in rat plasma were established respectively, and the matrix factors (MFs) and internal standard normalised matrix factors (IS normalised MFs) were measured. The results showed that the ion suppression of the μPen-ESI-MS/MS method for tacrolimus, flunarizine, and desloratadine was equal to or less than that of the LC-ESI-MS/MS method; the RSDs of the IS normalised MFs of all five drugs were less than 15%, which met the related requirements of the Pharmacopoeia of the People's Republic of China. Therefore, this study investigated the matrix effect of the μPen-ESI-MS/MS method for quantitative analysis of target drugs in plasma samples and provided new data for the application of μPen-ESI-MS/MS in bioanalysis.

This study aims to explore the mechanism of Arisaema cum Bile on epilepsy using combination of network pharmacology and patch clamp recording. Active ingredients of Arisaema cum Bile were collected from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and literatures. Epilepsy-related targets were identified from GeneCards and OMIM database. STRING platform was employed to perform protein-protein interaction (PPI), and David platform was used for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) enrichment analysis. The drug-ingredient-target-pathway-disease network was constructed with Cytoscape software. The animal experiments were approved by the Laboratory Animal Ethical and Welfare Committee Hebei Medical University. Nine compounds were detected as the active ingredients of Arisaema cum Bile, including chenodeoxycholic acid (CDCA), deoxycholic acid and β-sitosterol, etc. A total of 22 key potential targets were identified, including 5-hydroxytryptamine transporter (SLC6A4), gamma-aminobutyric acid receptor type A subunit alpha 2 (GABRA2) and neuronal acetylcholine receptor subunit alpha-7 (CHRNA7). These targets were associated with biological processes of serotonergic synapse, GABAergic synapse and ion transmembrane transport. Brain slice electrophysiology experiments revealed that β-sitosterol and CDCA inhibited the action potential (AP) of CA1 pyramidal neurons in the mouse hippocampus. Both β-sitosterol and CDCA affected the properties of AP, such as rheobase, delay and depolarization duration. In addition, the inhibitory effect of AP was more prominent when the two compounds were given together. Combining with network pharmacology and electrophysiological experiments, our study reveals the potential mechanisms of Arisaema cum Bile for the treatment of epilepsy in a "multi-ingredients, multi-targets and multi-pathways" manner. Our study provides a reference for further studies of Arisaema cum Bile.

To study the multivariate statistical analysis and metabolic regulation mechanism of rhubarb in the treatment of blood stasis syndrome through the ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF/MS). In this study, multivariate statistical analysis was used to comprehensively analyze the differential characteristics of metabolites with significant regulatory effect in plasma samples of blood stasis model rats, analyze the changes of differential metabolites of rhubarb regulating blood stasis syndrome, and analyze the pathway enrichment of identified metabolites. The results showed that the differentiation of plasma differential metabolites between the model group and the control group was good (Q² > 0.5), and 44 differential metabolites all had different degrees of callback. The expressions of PC(15∶0/20∶2(11Z, 14Z)), PC(18∶1(9Z)/18∶1(9Z)), salicylaldehyde and glycolic acid were down-regulated in the rat model of blood stasis syndrome, and rhubarb could up-regulate them. The expression levels of (±)8-HETE, taurodeoxycholic acid and γ-murocholic acid were up-regulated in the blood stasis rat model, which could be down-regulated by rhubarb. Differential metabolites are enriched in 97 metabolic pathways, involving lipid metabolism pathways, inflammatory factors and immune pathways, and steroid hormone synthesis pathways. This study clarified the mechanism of rhubarb in the treatment of blood stasis syndrome from the perspective of plasma metabolism, and provided a theoretical basis for the further development and clinical application of rhubarb. This study has been approved by the experimental animal Ethics Committee of Shaanxi University of Traditional Chinese Medicine (No. SUCMDL202103009002).

Invasive fungal infections are a tricky problem with high morbidity and mortality. The emerging of drug resistance worsens this problem. Therefore, developing novel antifungal agents is an urgent need to break these hurdles. Although protein kinase inhibitors have been extensively investigated in various fields such as cancer, diabetes, rheumatosis and so on, they are less explored in fungal infection. Previously, we found 12 protein kinase inhibitors with different antifungal activities, among them 5-iodotubercidin (5-Itu) was found to be the most potent antifungal agent with minimal inhibitory concentrations ranging from 2 to 4 μg·mL^-1. Moreover, 5-Itu displayed potent fungicidal effect, inhibition of hyphal formation and anti-biofilm activity. The mechanistic studies indicated that 5-Itu changed membrane sterol compositions and ultrastructures, increased the cell membrane permeability and induced apoptosis. Therefore, it needs to further study 5-Itu for the discovery of promising antifungal lead compounds.

To investigate the effect of ionic liquid based on choline and citronellic acid ([Cho] [CA], COCA) on the oral absorption of poorly soluble drug cyclosporin A (CsA), COCA was synthesized using choline and citronellic acid by one-step neutralization method, and then characterized by mass spectrometry, ¹H-NMR, and infrared spectrophotometry. Next, CsA-ionic liquid (CsA-COCA) was prepared by ultrasonic-assisted method and filled into enteric-coated capsules. After oral administration of CsA-COCA capsules or CsA suspension preparation in rats, CsA concentration in whole blood was assayed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, and the pharmacokinetic parameters were calculated by DAS 2.0 software. All animal care and experiments followed the approval of Institutional Animal Care and Use Committee at Peking University Health Science Center. The results indicated that compared with oral administration of 10 mg·kg^-1 CsA suspension, the area under the curve (AUC), half-life time (T_1/2), and mean residence time (MRT) of CsA obtained by oral administration the same dose of CsA-COCA increased by 2.81, 4.41, and 1.77 times, respectively. The COCA prepared in this study can significantly promote the oral absorption of CsA in rats, and prolong the half-life. This study can provide reference for the study of oral formulation of insoluble drugs such as CsA.

Histone deacetylases (HDACs) are a class of key enzymes that regulate epigenetics. There are 5 small-molecule HDACs inhibitors having been approved for anti-cancer therapy on the market. In recent years, there have been more and more studies on the antiviral aspects of HDACs inhibitors. This article classifies viruses into human immunodeficiency virus 1 (HIV-1), new coronavirus (SARS-CoV-2), Epstein-Barr virus (EBV) and other viruses, systematically summarizes the recent advances of antiviral effects of the HDACs inhibitors from the perspective of medicinal chemistry. This review aims to provide the researchers the convenience of accessing the latest advances of the antiviral effects of HDACs inhibitors, and to analyze the challenges and prospects of this field in future drug discovery.

To profile and characterize the ingredients absorbed into blood and their metabolites of the Eucommiae Cortex (EC) extracts in rats with renal fibrosis induced by adenine, and so as to provide a reference for investigation of the pharmacodynamic substances of EC. SD rats with renal fibrosis induced by adenine were intragastrically administered with the EC extracts, and the rat plasma samples were collected and analyzed by UHPLC-Q-TOF-MS/MS to identify the prototype ingredients absorbed into blood and their metabolites. The experiment was approved by the experimental Animal Ethics Committee from Nanjing University of Chinese Medicine (No. 202103A008). The results showed that a total of 24 prototype compounds were identified, including 9 lignans, 4 iridoids, 8 phenylpropanoids, and 3 organic acids. Furthermore, 30 metabolites were obtained by further analysis, including 9 lignans, 19 iridoids, and 2 organic acids. The results of this study can provide the valuable reference for further elucidation of the pharmacodynamic substantial basis and mechanism of EC in the treatment of renal fibrosis.

The heat shock protein 20 (Hsp20) gene family plays an important role in regulating the stress response and plant development. The characteristics of Hsp20 in Cannabis sativa (CsHsp20), however, are still unclear. We systematically analyzed the CsHsp20 family based on the whole-genome and transcriptome database of Cannabis sativa using a series of bioinformatical tools. A total of 35 CsHsp20 genes (CsHsp20-1-CsHsp20-35) were identified in Cannabis sativa; they distribute onto 9 chromosomes and belong to 10 subfamilies, each with similar protein motifs. The promoter region of the CsHsp20 genes contains a variety of hormone-responsive and stress-responsive cis-elements, indicating that CsHsp20 genes are involved in plant growth and development and various stress responses. Protein interaction analysis showed that CsHsp20 proteins interacted with other members of the Hsp family and were regulated by transcription factors Hop and HSFA2. Transcriptome data showed that the expression levels of CsHsp20 genes were different among different tissues of Cannabis sativa and across different developmental stages. CsHsp20 genes were highly expressed mainly in hemp seed and its maturation stage, suggesting that CsHsp20 gene family members regulate the growth and development of hemp seed. Our research lays a foundation for the studying the function of CsHsp20 gene family and the directional cultivation of high-quality non-psychoactive medicinal cannabis.