Objective: To study the secondary metabolites of marine-derived Aspergillus fumigatus MDCW-15. Methods: The secondary metabolites were isolated and purified by column chromatography over silica gel. And their structures were identified by the spectroscopic analysis of NMR and MS. The antifungal bioactivities were assayed by paper diffusion. Results: A new fumagillin compound 1 and a known compound 2 were isolated from the fermentation broth of marine-derived Aspergillus fumigatus MDCW-15. The antifungal bioactivities were assayed by paper diffusion. Compounds 1 and 2 showed antifungal activity against Candida albicans with an equal MIC value of 32.0 μg/mL. Conclusion: Compound 1 is a new compound named 2'-cis- fumagiringillin. Compounds 1 and 2 exhibit antifungal activities.

Objective: To determine the total saponins from Gynostemma pentaphyllum, the dammarane-type triterpenoids of its hydrolysate, and its hypoglycemic activity. Methods: Compounds from the acid hydrolyzate extracts and total saponins were isolated by silica gel, recrystal and preparative liquid chromatography, and their structures were identified by the NMR spectral analysis. The sensitive screening modles of α-glucosidase and PTP1B inhibitors were established in vitro. The inhibitory kinetics of compounds were also investigated. Using the method of computer aided drug design of active site, PTP1B interact with the strongest active compound for docking simulation. Results: Seven compounds were isolated from the acid hydrolyzate of total saponins, which identified as gpsapogenin A (1), 20(S)-panaxadiol (2), gypensapogenin F (3), 20(R)-protopanaxadiol (4), (23S)-3β- hydroxydama-20,24-diene-21-carboxylic acid 21,23-lactone (5), gypsapogenin A (6), and (20S,24S)-3β,20,21β,23β,25- pentahydroxy-21,24-epoxydammarane (7). Five compounds were isolated from total saponins, including (20R,23R)- 3β,20-dihydroxydammar-24-en-21-oic acid 21,23-lactone 3-O-[α-L-rhamnopyranosyl(1→2)][β-D-xylopyranosyl(1→3)]-6-O- acetyl-β-D-glucopyranoside (8), (20S,23S)-3β,20-dihydroxydammar-24-en-21-oic acid 21,23-lactone 3-O-[α-L-rhamnopyranosyl(1→2)][β-D-xylopyranosyl(1→3)]-6-O-acetyl-β-D-glucopyranoside (9), (20R,23R)-19-oxo-3β,20-dihydroxydammar-24-en-21-oci acid 21,23-lactone3-O-[α-L-rhamnopyranosyl-(1→2)][β-D-xylopyranosyl(1→3)]-α-L-arabinopyranoside (10), (20S)-3β,20,21- trihydroxydammar-23,25-diene 3-O-{[α-L-rhamnopyranosyl(1→2)][β-D-xylopyranosyl(1→3)]-β-D-glucopyranosyl}-21-O-β- D-glucopyranoside (11), and (20S,23S)-3β,20-dihydroxydammar-24-en-21-oic acid and 21,23-lactone 3-O-[α-L-rhamnopyranosyl(1→2)][β-D-xylopyranosyl-(1→3)]-β-D-glucopyranoside (12). Conclusion: Beside compound 4, the other compounds showed inhibitory activity against α-glucosidase and PTP1B. For the α-glucosidase and PTP1B inhibitions assay, compound 9 indicated the strongest inhibitory effect with IC50 2.10 and 1.07 μmol/L, respectively.

Objective: To study the chemical constituents of ethyl acetate extract from the whole herb of Pholidota articulata. Methods: Silica gel and Sephadex LH-20 gel column chromatographic techniques were used to separate and purify the chemical constituents. Their structures were elucidated based on NMR spectroscopic and reported data. Results: A total of 17 compounds were isolated from 78% ethyl acetate extracts of P. articulata and identified as flavidin (1), flaccidin (2), imbricatin (3), coelonin (4), lusianthridin (5), hircinol (6), gigantol (7), batatasin III (8), 5,3'-dihydroxy-3-methoxybibenzyl (9), cirrhopetalidin (10), β-sitosterol (11), stigmasterol (12), glut-5-en-3-ol (13), laurostearic acid (14), 4, 4'-dihydroxydiphenylmethane (15), 3-methoxy-benzaldehyde (16), and trans-cinnamic acid (17). Conclusion: Compounds 3-17 are isolated from this plant for the first time. In addition, compounds 9, 10, 13, and 16 are found in the genus Pholidota for the first time.

Objective: To construct molecular network and analyze rapidly the saponins of six species of Clematis plants. Methods: The mass spectral data, acquired with UHPLC-LTQ Orbitrap MS, were uploaded to the GNPS analysis platform to build molecular network, visualized by Cytoscape software. On the other hand, the triterpenoid saponins from six plants were identified on the basis of the fragmentation regularity of the standard and the reported literature. Results: Twenty-five triterpenoid saponins, including 16 hederagenin saponins and nine oleanolic acid-type saponins, were determined from six kinds of plants. The distribution of the triterpenoid saponins in the six kinds of plants were profiled by the pie chart of each node in molecular network. Twenty compounds were found in at least two species of Clematis. Clematichinenoside A and oleanolic acid 3-O-ribopyranosyl-(1→3)-α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranoside were the common constituents in five species. Six saponins were distributed in in single species of Clematis. Conclusion: Compared with traditional phytochemical methods, the molecular network technology of UPLC-LTQ-Orbitrap MS can quickly and visually distinguish different triterpenoid saponins in six kinds of plants. There are similarities and differentiates among the triterpenoid saponins in the six kinds of plants, which provides the basis for the substitution of medicinal materials.

Objective: To establish a rapid and accurate analytical method for the identification of complex system of traditional Chinese medicine, and to systematically clarify the chemical composition of sesquiterpenes in Alpinia oxyphylla. Method: On the basis of optimizing the extraction process of sesquiterpenes, the accurate molecular weight and secondary fragment ions information of unknown compounds were captured by ultra-high performance liquid chromatography-quadrupole/orbitrap high resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS). Compared with the relative retention time and mass spectrometry data of the reference substance, combined with relevant references and databases, the sesquiterpene unknown compounds in the fruits of A. oxyphylla were accurately and rapidly characterized. Results: A total of 24 sesquiterpenes were identified and classified into four categories according to their skeleton structure, including nine eudesmane-type, six cadinane-type, eight eremophilane-type, and one oplopanone-type. Conclusion: In this study, the established analytical method was used to realize the rapid and accurate identification of sesquiterpenes in the fruits of A. oxyphylla, which provided a theoretical basis for the research on the pharmacodynamic substance basis and quality control of the fruits of A. oxyphylla.

Objective: Sialic acid (SA)-modified chlorogenic acid (CA) liposomes (CA-SAL) was prepared by response surface design to investigate its in vitro cytotoxicity and uptake. Methods: CA-SAL was prepared by a modified reverse-phase ethanol injection method. Sephadex G50 column was used to separate the CA-loaded liposomes and the free CA. The drug concentration was determined by HPLC method and the encapsulation efficiency was calculated. With encapsulation efficiency and drug loading as indicators, Box-Behnken response surface design experiments were used to optimize the prescription process of CA-SAL. The MTT method was used to evaluate the cytotoxicity of CA-SAL on human lung cancer cells A549. Inverted fluorescence microscope was used to investigate the uptake of CA-SAL by A549 cells. Results: The optimized preparation conditions: hydrogenated soybean lecithin-CA ratio at 15:1, hydration temperature 60 ℃, ultrasonic power 400 W. The average particle size of CA-SAL was (90.13 ± 0.51) nm, the polydispersity index (PDI) was 0.16 ± 0.01, the zeta potential was (-25.3 ± 0.5) mV, the encapsulation efficiency was 57.8%, RSD was 0.1%. MTT results showed that the inhibitory effect of CA-SAL on A549 cells was significantly greater than CA-CL. Greater cellular uptake of CA-SAL was observed compared with CA-CL. Conclusion: CA-SAL prepared by response surface optimization has a uniform particle size and good stability. SA-modified CA-loaded liposomes could enhance cellular uptake and cytotoxicity of human lung cancer cell A549 in vitro.

Objective: To investigate the effect of three types of precipitation inhibitors (PPI) HPMC K4M, HPMC AS MG and Soluplus on the pH-induced supersaturated phase behavior of dl-tetrahydropalmatine (dl-THP) at oral clinical doses. Methods: dl-THP pH solubility phase diagram and desaturation curve during pH-shift were drawn, and the solubility phase diagram was used to support dl-THP phase behavior. Area under the concentration-time curve and supersaturation ratio were used to analyze the effect of PPI on the phase behavior of dl-THP; Polarized light microscope and differential scanning calorimetry were used to analyze the precipitation properties. Results: Under the clinical dosage, the maximum supersaturation of dl-THP during the pH-shift was 3.93, and the supersaturation was lost over time; HPMC K4M, HPMC AS MG, and Soluplus could all maintain the supersaturation within 180 minutes during the pH-shift dissolution. HPMC K4M, HPMC AS MG, and Soluplus maintained supersaturation levels of 1.19, 1.89 and 1.36 respectively at a concentration of 5%, 1.30, 2.35 and 1.86 at a concentration of 20%, and 1.30, 2.60 and 2.07 at a concentration of 50%. Polarized light microscopy and differential scanning calorimetry results showed that crystalline precipitation occurred. Conclusion: All precipitation inhibitors can improve the pH-induced supersaturated phase behavior of tetrahydropalmatine, and this improvement behavior varies with the type and concentration of precipitation inhibitors. HPMC AS MG has the best effect.

Objective: To optimize the infiltration process of Astragalus (Astragalus membranaceus var. mongholicus) medicinal materials by Box-Behnken response surface method. Methods: Based on the HPLC-DAD-ELSD and response surface design method, the qualified rate of decoction pieces, the content of index components and bending inspection were used as comprehensive inspection indicators, and the three factors of infiltration were selected for response surface experimental design to optimize the infiltration process of Astragalus medicinal materials parameter. Results: The best infiltration process was as following: infiltration temperature was 20 ℃, with water addition of 1:0.988 for 6 h. Under this process, the qualified rate of Astragalus pieces was 95.81%, the content of calycosin-7-glucoside was 0.072%, and the content of astragaloside IV was 0.276 %. Combining fingerprint analysis and heat map analysis, the material basis of A. membranaceus var. mongholicus changed during the infiltration process. The infiltration parameters should be strictly controlled during the infiltration process to ensure uniform quality of the pieces. Conclusion: The optimized Astragalus medicinal material infiltration process is stable and feasible with good reproducibility, which can provide a reference for the mass production process development of Astragalus medicinal slices.

Objective: The discrete element method (DEM) was used to simulate the angle of repose of Chinese medicine extract powders. The contact parameters between particles and between particles and geometry were calibrated. Methods: The licorice extract powder, the extract powders of Angelicae Pubescentis Radix (Duhuo), microcrystalline cellulose (MCC) and ethyl cellulose (EC) were taken as the research objects. DEM was performed based on the Hertz-Mindlin with JKR Cohesion contact model and particle scaling. The Plackett-Burman design was used to screen out the critical contact parameters that had significant impact on the simulation measurement of the angle of repose. Then, the steepest climbing design was used to determine the best area of critical contact parameters. After that, a regression model between the contact parameters and the simulated angle of repose was established according to the Box-Behnken test results, and the best contact parameter values were optimized and verified. Results: The critical contact parameters selected were particle-particle rolling friction coefficient, particle-particle restitution coefficient and particle-stainless steel restitution coefficient. The calibration range of the built regression model was from 33.30° to 43.64°. The absolute values of the relative error between the simulated values and the experimental values of the angle of repose for four powders were all less than 2.0%, indicating that the established calibration method was accurate and reliable. Conclusion: This article proved the feasibility of calibrating the DEM micromechanical parameters of the Chinese medicine particle system through the macroscopic physical parameter, and laid the foundation for accurate simulation of Chinese medicine pharmaceutical processes like powder mixing and conveying.

Objective: In order to provide a scientific basis for the quality control of Kunxian Capsules (KC), HPLC characteristics chromatogram combined with multi-components determination was established. Methods: The analysis was performed on Agilent Zorbax SB-C18 column (250 mm × 4.6 mm, 5 μm), using acetonitrile and 0.1% phosphoric acid solution as the mobile phase at a flow rate of 0.8 mL/min for gradient elution, the column temperature was 33 ℃, and the detection wavelength was 270 nm. The fingerprints of 15 batches of KC were established and evaluated by the similarity evaluation system of TCM (2012A version), hierarchical cluster analysis and discriminant analysis of partial least squares. Furthermore, the content of hyperoside, epimedin A, epimedin B, epimedin C, icariin and baohuoside Ⅰ were determined. Results: The HPLC fingerprint with 21 common peaks of KC was established, and the similarities of samples were over 0.9. The linearity relationships separated with hyperoside, epimedin A, epimedin B, epimedin C, icariin and baohuoside Ⅰ were good, and the contents of the above-mentioned components in 15 batches of preparations were 2.817-7.527, 7.287-9.103, 8.730-18.675, 33.377-70.371, 35.297-50.291 and 4.059-9.079 mg/g, respectively. Conclusion: The combination methods of HPLC characteristic chromatograms and simultaneous determinations of multiple components are rapid, simple and reproducible, which can provide methodological reference for the quality control of KC.