OBJECTIVE To predict the potential quality marker (Q-Marker) components of Suanzaoren Decoction based on the prototype chemical composition of in vivo by using network pharmacology. METHODS Firstly, the plasma samples and urine samples of rats were collected within 4 h and 24 h after intragastric administration of Suanzaoren Decoction, respectively. Then, based on the chemical components found in vivo, the key action targets and key pathway were obtained by network pharmacology, and the network map of "component-target-pathway" was carried out to predict the quality markers of Suanzaoren Decoction against insomnia, anxiety and depression. RESULTS A total of 20 prototype compounds were detected in rats. The 23 core targets were predicted and 14 prototype components associated with pharmacodynamic efficacy were screened through network pharmacology, the 14 components including jujuboside A, enoxolone, ferulic acid, magnoflorine, liquiritigenin, isoliquiritigenin, poricoic acid A, spinosin, coclaurine, timosaponin BII, glycyrrhizic acid, jujuboside B, liquiritin and senkyunolide A played multiple targets and multiple pathways to regulate insomnia, anxiety, depression. CONCLUSION It is predicted that the 14 chemical components are considered as potential quality markers of Suanzaoren Decoction by analyzing prototype chemical composition in vivo combined with network pharmacology. The results can provide reference for the quality control of Suanzaoren Decoction, and lay a foundation for elucidating the mechanism of its pharmacodynamic substances.

OBJECTIVE To explore the antiepileptic activity of QO-83, a novel KCNQ channel opener, by establishing and optimizing a 6 Hz corneal kinked model, and to provide a scientific basis for the application of QO-83 in drug-resistant epilepsy. METHODS The mice were divided into control group, model group, positive drug levetiracetam (100 mg·kg^-1) group, control drug carbamazepine (50 mg·kg^-1) group, and QO-83 low (2 mg·kg^-1), medium (4 mg·kg^-1), and high (6 mg·kg^-1) dose groups. The 6 Hz kindled mice were established, and drugs was injected intraperitoneally. After 30 min, 6 Hz corneal stimulation was applied again to observe its protective effect on the animal. And set up a series of behavioral experiments: tail suspension test, T-maze test, and new object recognition test, observe the immobility time, selection accuracy, and recognition index of mice respectively, to evaluate its impact on animal depressive tendencies and memory abilities. Immunofluorescence staining was performed on 6 Hz model mice to observe the expression changes of c-Fos protein and evaluate the protective effect of QO-83 on specific brain regions. Observe the expression changes of its target KCNQ2 protein and evaluate its impact on target protein expression. RESULTS The established model mice were not sensitive to the action of carbamazepine (50 mg·kg^-1), but effective against levetiracetam (100 mg·kg^-1). When given 2, 4 and 6 mg·kg^-1 QO-83, dose-dependent anti-epileptic effects can be observed, which significantly reduced the incidence and duration of seizures in ignited mice. The 4 mg·kg^-1 of QO-83 can significantly reduce the immobility time of epileptic mice in tail suspension experiments, increase the accuracy of mice in T-maze test, and increase the recognition index (RI) of mice in new object recognition test. QO-83 can significantly downregulate the expression of c-fos in the hippocampus and piriform cortex of epileptic mice, and upregulate the expression of KCNQ2 protein in the CA3, DG regions and their surrounding fibers and PIR regions of late-stage model mice. CONCLUSION Compound QO-83 has good anti drug-resistant epilepsy activity, and its protective effect on epileptic animals is better than the positive drug levetiracetam. At the same time, it also has the effect of improving the behavior of epileptic animals, demonstrating the therapeutic potential for drug-resistant epilepsy. The mechanism of action may be related to upregulating the expression of the target protein KCNQ2.

OBJECTIVE To establish an UHPLC-MS/MS method for the determination of six alkaloids in Tianma capsule. METHODS Phenomenex Kinetex C₁₈ (2.1 mm×100 mm, 2.6 μm) column was used for separation. The mobile phase consisted of methanol and 0.1% formic acid (containing 2.5 mmol·L^-1 ammonium acetate) solution (gradient elution). The flow rate was 0.3 mL·min^-1 and the column temperature was maintained at 35 ℃. Electrospray positive ion source was used for mass spectrometry detection by multiple reaction monitoring mode. RESULTS The liner range of calibration curve was 79.38-3 969 ng·mL^-1 (r=0.999 9), 18.60-929.8 ng·mL^-1 (r=0.999 8), 38.20-1 910 ng·mL^-1 (r=0.999 9), 1.264-252.8 ng·mL^-1(r=0.999 3), 1.196-239.2 ng·mL^-1(r=1.000 0) and 1.268-253.6 ng·mL^-1(r=1.000 0)for benzoylmesaconine, benzoylaconine, benzoylhypaconine, mesaconitine, hypaconitine and aconitine. The RSD of repeatability test (content) was 0.5%-3.2%. The average recoveries was in the range of 98.3%-105.3%. RSD was 1.0%-3.4%. CONCLUSION The method has good sprcificity, sensitivity and accuracy, and it is suitable for the analysis of six alkaloids in Tianma capsule.

OBJECTIVE To design, synthesize and evaluate a series of 3', 4'-ethylendioxy chalcone derivatives as monoamine oxidase B (MAO-B) inhibitors, and summarize the structure-activity relationship (SAR). METHODS The targeted compounds were synthesized via Claisen-Schmidt condensation reaction starting from 6-acetyl-1, 4-benzodioxan and corresponding benzaldehydes. The inhibition of these compounds on human MAO-B (hMAO-B) was determined, and the inhibiting selectivity, dynamics and reversibility were investigated as well. The binding mode between active compounds and hMAO-B was revealed by molecular docking study. Additionally, the inhibitory effect of active compounds on the proliferation of BV2 cell line was determined by MTT assay. RESULTS Sixteen targeted compounds were successfully prepared. Most compounds showed good inhibitory effects on hMAO-B. Representative compounds 9 and 13 exhibited IC₅₀ values of 0.021 and 0.042 μmol·L^-1, respectively, which showed high inhibiting selectivity towards hMAO-B. Both compounds acted as competitive and reversible hMAO-B inhibitors. The main interactions between active compounds and hMAO-B were hydrophobic interaction and hydrogen bond. The most active compound 9 exhibited low cytotoxicity in BV2 cells. CONCLUSION This class of 3', 4'-ethylendioxy chalcone derivatives represent potential novel inhibitors of hMAO-B, and compound 9 could be further investigated as a potent lead for future studies.

The discovery of drug targets is crucial for understanding the mechanism of drug action and facilitating the development of novel drug therapeutics. Microscale thermophoresis (MST), renowned for its minimal sample consumption, rapid detection speed, high sensitivity, and the absence of the need for protein immobilization, has emerged as a pivotal tool in drug target research. This article outlines the strategies for identifying drug targets, with a focus on elucidating the principles of MST and its application in drug target discovery. Furthermore, it summarizes the promising prospects of MST in this field. The applications of MST are found in both forward and reverse strategies for target discovery, enabling the identification of target proteins for compounds, single herbal ingredients, and compound prescriptions, as well as facilitating drug screening. Additionally, the integration of MST with other molecular interaction techniques, such as surface plasmon resonance (SPR), provides a potent arsenal for studying the interactions between drugs and their targets. Despite certain limitations, MST holds immense potential for application in the realms of novel drug development and drug mechanism research.

OBJECTIVE To prepare osthole(OST) nanocrystallization and evaluate its characterization. METHODS OST-NSs were prepared by a media grinding method, and the average particle size and polydispersity index (PDI) were used as indicators to optimize the formulation and process parameters. The crystal morphology, crystal form, and interaction between OST-NCs and stabilizers were characterized. Their surface wettability, equilibrium solubility, and in vitro dissolution in various media were investigated, and the f₂ value was used to evaluate the similarity of the dissolution curves. RESULTS The formulation and process parameters for preparing OST-NCs were as follows: OST (3%): PVP-VA64, sodium deoxycholate 25∶5∶1, the volume ratio of grinding beads (0.4-0.6 mm) to OST suspension was 2∶1, and it was ground at 450 r·min^-1 for 70 min, and 9% mannitol was used as a lyophilized protective agent to prepare OST-NCs. The stability of OST-NCs decreases with increasing temperature. After reconstitution, the particle size of OST-NCs was (354.2±9.857) nm, the PDI was (0.259±0.023), and the Zeta potential was (-22.2±0.896) mV. OST-NCs basically maintain the rod-shaped crystal structure. There is no interaction between OST and the stabilizer. The surface wettability of OST-NCs is better than that of OST and its physical mixture. The equilibrium solubility of OST-NCs in pure water is 231% that of OST. Among the six dissolution media, the dissolution rate and cumulative dissolution of OST-NCs were significantly better than those of OST and its physical mixture. Additionally, the f₂ values for the physical mixtures were greater than 50, whereas those for OST-NCs were less than 50, as compared with the dissolution curves of OST. CONCLUSION The results show that the reproducibility of OST-NCs is good during their preparation. The grinding temperature should be reduced, and the grinding time should be optimized. The dissolution behavior of OST-NCs is significantly different from that of OST. The reduction of particle size is the main reason for the improved water solubility of OST-NCs. These results suggest that the nanocrystallization strategy based on media grinding can effectively improve the water solubility and hydrophobicity of OST and has a good application prospect in the development of new OST drugs.

OBJECTIVE To determine the antioxidant activities of Gossampim Flos waterextracts,establish UPLC fingerprints and study the spectral effect relationship. METHODS Based on the scavenging rates of 2, 2-diazo-di (3-ethyl-benzothiazolin-6-sulfonic acid) diamiammonium salt (ABTS) and 1, 1-diphenyl-2-picrohydrazyl radical (DPPH), the fingerprint of different parts (petal, calyx and stamen) of 12 batches of Gossampim Flos were established by UPLC method, and similarity analysis were carried out. Grey correlation analysis (GRA), Spearman analysis, stepwise regression analysis and partial least squares regression(PLSR) analysis were used to study the relationship between antioxidant spectrum effect. RESULTS Eight chromatographic peaks were identified by fingerprint identification of water extracts from different parts of 12 batches of Gossampim Flos. Mangiferin, quercetin, rutin, vitexin and other compounds were the main active components of Gossampim Flos and its different parts for antioxidant activities. CONCLUSION The antioxidant activity of Gossampim Flos and its different parts are the result of the combined effect of multiple components. This study can provide a comprehensive reference for the basis and quality control of antioxidant active substances of Gossampim Flos and its different parts.

OBJECTIVE To prepare puerarin/daidzein porous nanocrystals using polyethyleneglycol (PEG)and chitosan(CS)as carrier aterialsand evaluate their physicochemical properties and in vitro characteristics. METHODS The drug loading rate and entrapment rate were used as indicators to optimize the prescription,and the insoluble drug puerarin-daidzein was encapsulated in the form of inclusion compound by two-step method β-CD-puerarin-daidzein-PEG-CS nanocrystals. The inclusion degree of puerarin-daidzein nanocrystals was determined by Fourier transform infrared spectroscopy, thermogravimetry, X-ray diffraction, scanning electron microscope, antioxidant and bacteriostatic tests to verify the feasibility of the preparation method. And investigate its drug release behavior in simulated gastrointestinal fluid and gastric environment, and fit the drug release model. RESULTS The inclusion compound prepared by saturated aqueous solution method was the best when the volume fraction of inclusion compound was 1.000% acetic acid. Its cumulative release rate is about 90%, drug loading and inclusion rate are (26.13±0.74)% and (78.39±2.23)%, respectively. Puerarin-daidzein nanocrystals have many and dense pore diameters, and have good antioxidant performance. Obvious inhibition zone against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa can be observed, showing good antibacterial performance. CONCLUSION Puerarin-Daidzein porous nanocrystals can significantly improve the dissolution of insoluble drug daidzein, which lays a foundation for its application in the field of biomedicine.

OBJECTIVE To analyze the difference of chemical components of different processed products of Polygonati Rhizoma produced in Shaanxi Province. METHODS Ultra-high performance liquid chromatography coupled with hybrid quadrupole-orbitrap mass spectrometry (UPLC-Q-Exactive Orbitrap-MS) was developed to determine the chemical components of different processed products of Polygonati Rhizoma produced in Shaanxi Province. The data was analyzed by principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). The structures of chemical markers of different processed products of the plants were identified based on accurate primary mass spectrometry and secondary mass spectrometry fragment ion, combined with the reference map, software database searching and related literature. RESULTS A total of 45 components were identified, there were 23 chemical components with significant differences distinguished by the method of OPLS-DA, including 13 amino acids, 5 alkaloids, 2 saccharides, 1 coumarin, 1 saponin, 1 organic acids. CONCLUSION There are some chemical differences among the three products. This study can provide material basis for the quality control and pharmacodynamic research of processed products of Polygonati Rhizoma.

OBJECTIVE To screen the quality markers (Q-marker) of Rhododendron molle based on HPLC-ELSD and network pharmacology, compare the contents of quality markers in different parts, different flowering periods and different producing areas of R. molle, and explore the potential medicinal value of R.molle and speculate its possible mechanism of action. METHODS HPLC-ELSD was used to establish the fingerprint of R. molle, and hierarchical clustering analysis (HCA), principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were carried out. The network diagram of ' component-target-pathway-pharmacological effect-efficacy ' was constructed by network pharmacology method, and the disease prediction was carried out. The quality markers of R. molle were screened and quantitatively analyzed. RESULTS In this study, the fingerprints of 11 batches of Rhododendron molle were established, and total of 10 common peaks were calibrated. Four differential components were obtained after analysis. It was predicted that rhodojaponin-Ⅲ, rhodojaponin-Ⅱ, hyperoside and quercitrin were candidate components of quality markers of R. molle and network pharmacology analysis was performed. It involved 84 target proteins, including ATK1, TNF, INS, etc., acting on 159 signaling pathways, and had potential therapeutic effects on tumors, autoimmune diseases, and cardiovascular diseases. The results of component content determination showed that the flowering of Rhododendron molle might have better curative effect, and the S10 origin was the best. CONCLUSION The quality markers of R. molle are predicted by chemical pattern recognition, fingerprint and network pharmacology. It is proved that R. molle could treat diseases through multiple targets and multiple pathways, which provides a reference for improving the establishment of quality control standards of R. molle and further exploring the mechanism of disease treatment.