OBJECTIVE: To compared the effect of different drying methods on drying characteristics, water effective diffusion coefficient and biased activation energy of Codonopsis Radix and to definite 3 different drying methods of varying temperature(45-55-60, 60-55-45, 60-45-60℃) and 3 constant temperature(45, 55, 60℃) on drying characteristic curves of different commercial grades of Codonopsis Radix. METHODS: Used R2, χ2 and RMSE as evaluation indexes, 10 typical drying kinetic models were selected to fit the drying curve of Codonopsis Radix, and the effective moisture diffusion coefficient and biased activation energy under different drying method were calculated. RESULTS: It was found that the Midilli model could well describe the drying process of different commercial grades of Codonopsis Radix, the water ratio of Codonopsis Radix showed an exponential downward trend. If the initial drying temperature was set above 55℃, the maximum drying rate could be reached within 2 h. And commercial grades temperature had certain influence on the effective water diffusion coefficient of Codonopsis Radix. Under the same temperature condition, the average speed of moisture migration during drying of Codonopsis Radix was:first-class> second-class>third-class, and the Deffwere 10.433 9×10-8, 5.545 2×10-8, 2.249 6×10-8·m2·s, respectively. The calculated bias activation energy of Codonopsis Radix was 2.943×104-4.378×104 J·mol-1, the order of bias activation energy of different drying methods was as follows:60-55-45℃ variable temperature<60-45-60℃ variable temperature<45-55-60℃ variable temperature<55℃ constant temperature<60℃ constant temperature <45℃ constant temperature, which indicated that the moisture in the medicinal materials was more likely to evaporate and overflow and consumes less energy than the constant temperature drying. In particular, the bias activation energy of 60-55-45℃ drying method was 77.54% and 81.86% of the other 2 variable temperature drying methods, which were 67.22%, 75.13% and 74.26% of the 3 kinds of constant temperature drying. CONCLUSION The use of cooling mode in the drying process can save more time and energy, and can provide experimental basis for the improvement of drying technology and optimization of drying process of Codonopsis Radix.

OBJECTIVE: To investigate the effects of compatibility of Gardeniae Fructus and Rhododendri Mollis Flos on the pharmacokinetic behavior of rhodojaponin II and rhodojaponin III of Rhododendri Mollis Flos. METHODS LC-MS/MS of rhodojaponin II and rhodojaponin III in plasma of rats was developed. The method was then applied to study the blood concentrations of rhodojaponin II and rhodojaponin III in rats after oral compatibility administration of Gardeniae Fructus and Rhododendri Mollis Flos and single decoction administration of Rhododendri Mollis Flos, respectively, then their pharmacokinetic parameters were calculated and statistical analysed. RESULTS: The calibration curve was good linearity(r>0.999) in the range of 1-200 ng·mL-1 for rhodojaponin II and 1-100 ng·mL-1 for rhodojaponin III, the precision of quality control samples was less than 12% and the accuracy was less than 20%. After administration of compatibility of Gardeniae Fructus and Rhododendri Mollis Flos and Rhododendri Mollis Flos alone, the AUC0-t of rhodojaponin II in vivo was(260.44±51.67) and (213.39±59.03)h·ng·mL-1, respectively, and the AUC0-t of rhodojaponin III was (60.97±22.78) and (22.38±5.55)h·ng·mL-1, respectively. Compared with single decoction of Rhododendri Mollis Flos administration group, the T1/2 and MRT(0-t)of the rhodojaponin II were significantly increased, the AUC0-t, T1/2, Tmax and CL of the rhodojaponin III were also significantly rised after administration of compatibility of Gardeniae Fructus and Rhododendri Mollis Flos. CONCLUSION After the compatibility of Gardeniae Fructus and Rhododendri Mollis Flos, the rate of absorption and the distribution volume are increased of rhodojaponin III in rats, while the elimination rate has decreased, the T1/2 of rhodojaponin II and rhodojaponin III are extended, but don't affect the absorption rate of rhodojaponin II in rats.

Abstract OBJECTIVE To clarify the resource status and diversity of endemic medicinal plants in Shaanxi province. METHODS The species specificity, species composition, faunal composition, family and genus types, medicinal value and endangerment degree of endemic medicinal plants in Shaanxi province were studied by literature review.RESULTS There were 713 species of 331 genera and 101 families endemic to Chinese medicinal plants in the study area. Fifteen species were naturally distributed only in Shaanxi province, and the remaining 698 species were also naturally distributed in other provinces of China. Among the 713 species, 233 species(69 families, 159 genera) were not collected from the fourth resource census in Shaanxi province. There were 11 species of pteridophytes in 7 families and 11 genera, 14 species of gymnosperms in 4 families and 10 genera, 627 species of dicotyledons in 82 families and 278 genera, and 59 species of monocots in 8 families and 32 genera. The endemic life forms of medicinal plants in the study area were mostly herbaceous, followed by shrubs and trees, and semi-shrubs and epiphytes accounted for the least. There were 9 families with ≥ 20 species and 4 families with ≥ 10 species in the study area. The 90 families belonging to the endemic species of medicinal plants in Shaanxi province were divided into 13 distribution types and 9 variations, and the tropical distribution(2-7 categories) had a total of 34 families. There were 5 endemic species of medicinal plants in the study area under the national class I key protection, and 14 species under the national class II key protection. There were 26 species of plants under local key protection in Shaanxi province. There were 21 plants that could be used as original plants for medicinal materials included in the Pharmacopoeia of the People's Republic of China(2020 edition). CONCLUSION The endemic species of medicinal plants in Shaanxi province are rich in resources and have good medicinal value. However, the growing environment of some plants is harsh and human damage is serious. Multiple protection measures should be taken to maintain the species diversity and sustainable development of resources in the study area.

Abstract OBJECTIVE To investigate the effect and mechanism of flavonoids from Sophora flavescens Ait. on testicular tissue damage in male mice induced by local heat stress in the scrotum. METHODS TCMSP database was used to screen the targets of flavonoids in Sophora flavescens Ait., and the bioinformatics analysis was performed on the target. The mouse model of scrotal heat stress was used and the flavonoids of Sophora flavescens Ait. was used for intervention. The sperm density and sperm aberration rate of mice in each group were measured, and the morphological changes of testicular tissue were observed. Tumor necrosis factor-α (TNF-α) and interleukin 17(IL-17) mRNA and protein levels in testicalar were detected of by q-PCR and Western blotting. Na+-K+-ATPase, Mg2+-ATPase, Ca2+-ATPase, lactate dehydrogenase(LDH), sorbitol dehydrogenase(SDH) activity, malondialdehyde (MDA), NO, TNF-α level and the content of testosterone in serum were detected in tissue homogenate. RESULTS Heat stress could lead to the decrease of sperm density and increase of aberrant sperm, the obvious thinning of testicular spermatogenic epithelium, the decrease of cell level and quantity, the significant decrease of ATPase, LDH, SDH activities, and the increase of MDA, NO content, TNF-α and IL-17 expression in testicular tissue. After the intervention with 250, 500 mg·kg-1·d-1 flavonoids of Sophora flavescens Ait., the quality of sperm and the damage of testicular tissue morphology were improved. The level of TNF-α and IL-17 in serum and testicular tissue were decreased, and the activity of ATPase, SDH and the level of testosterone were increased. CONCLUSION The mechanism of flavonoids of Sophora flavescens Ait. is through inhibiting the inflammatory factor TNF-α and IL-17 levels, improve the anti-lipid peroxidation ability and inhibite the role of NO, enhance the activity of energy enzymes in spermatogenesis, improve the level of serum testosterone, and improve the reproductive disorders caused by heat stress.

Abstract OBJECTIVE To explore the material basis and mechanism of Crataegi Fructus in improving metabolic hypertension(MH) by using network pharmacology and molecular docking technique.METHODS The components of Crataegi Fructus were collected by HERB, ETCM database and literature survey; screening all ingredients of Crataegi Fructus to improve MH targets through databases such as SwissTargetPrediction and GeneCards; build "active ingredient-target-disease" network of Crataegi Fructus with Cytoscape software; DAVID was used to analyze GO enrichment and KEGG pathway. The core components and core targets were verified by molecular docking with Autodock software. RESULTS The total of 89 active components were screened from Crataegi Fructus and acted on 84 targets. Among them, the core active components of Crataegi Fructus to improve MH were maslinic acid, fomefficinic acid B, linolenic acid, linoleic acid, methyl-n-nonylketone, apigenin, ursolic acid, etc. The core targets were CYP19A1, PPARA, ESR1, PTGS2, PPARG, NR3C1, MMP9, TNF, etc. The mechanism of action mainly involved multiple signaling pathways such as inflammation, glycolipid metabolism, and vascular endothelial function. Molecular docking showed that the core active ingredients of Crataegi Fructus had high affinity with core targets. CONCLUSION Crataegi Fructus may regulate multiple signaling pathways such as TNF, IL-17, AGE-RAGE, HIF-1, cGMP-PKG through multi-component regulation, thereby inhibiting inflammatory response, improving glucose and lipid metabolism abnormalities, and improving vascular endothelial function, so as to comprehensively exert the role of improving MH in various aspects.

Abstract OBJECTIVE To explore the intervention mechanism of Guizhi Fuling pills on breast cancer based on multi-data platform and bioinformation technology, and to verify the analysis results by cell test. METHODS The data set related to breast cancer was downloaded from GEO database to analyze the differential genes of breast cancer. The main active components and target genes of Guizhi Fuling pills were screened from TCMSP database. The key target genes of Guizhi Fuling pills in the treatment of breast cancer were mapped by the two groups of target genes. TCGA database was used to analyze the expression of key target genes in breast cancer. Through TIMER, CPTAC Data Portal, and Kaplan-Meier plotter, TISIDB, SangerBox and other data platforms, the relationships of the key genes expression and immune micro-environment, immune infiltration level, genomic heterogeneity, immune subtypes, molecular subtype, and poor prognosis were analyzed in breast cancer. KEGG pathway enrichment of key genes was performed searching for possible signaling pathways by Metascape analysis platform. Finally, CCK-8 assay, cell scratch assay, Transwell chamber assay and Western blotting technique were used to verify the results in vitro. RESULTS There were 42 active components and 185 targets in Guizhi Fuling pills, and 14 key targets related to the treatment of breast cancer were mapped with GEO database. Six key target genes for the treatment of breast cancer were obtained by comparison with breast cancer differential genes in TCGA. The expression of these 6 key genes was strongly correlated with the levels of 6 immune cells, 3 immune microenvironment scores, immune subtypes and molecular subtypes in breast cancer(P<0.05), also showed consistency in the correlation of genomic heterogeneity, and was closely associated with poor prognosis(P<0.05). KEGG enrichment analysis showed that these 6 genes were mainly enriched in PI3K/Akt signaling pathways. Cell test showed that Guizhi Fuling pills could significantly inhibit the proliferation, migration and invasion of HCC1937 cells, and also reduce the relative expression of p-Akt/Akt and p-PI3K/PI3K proteins in HCC1937 cells in a dose-dependent manner. CONCLUSION Guizhi Fuling pills may interfere with breast cancer by blocking PI3K/Akt signaling pathway and regulating the tumor immune microenvironment.

Abstract OBJECTIVE To introduce the developing procedure of reference standards of nitrosamines by taking 1-methyl-4-nitrosopiperazine(MNP) as example and discuss the problems needing attention when using nuclear magnetic resonance(NMR) quantitative method. METHODS The structure of the material was confirmed by mass spectrometry, infrared spectrum and nuclear magnetic methods. In terms of quantitative assessment, the purity of the material was analyzed by HPLC, and the water was investigated. The content of MNP was determined by mass balance method, the content of the material was verified by NMR quantitative method. RESULTS MNP was consistent with its structure. In the quantitative NMR investigation, it was found that the use of different internal standards had a great impact on the calibration results. CONCLUSION Since MNP is basic, it is easy to reduce the final determination result by using an acidic internal standard in NMR quantitative analysis. Therefore, it is suggested that an appropriate internal standard should be selected for this kind of sample in the process of NMR quantitative determination.

Abstract OBJECTIVE To identify and analyze two unknown degradation impurities in nimodipine oral solution. METHODS The chemical structure of the unknown impurity was deduced by two-dimensional liquid chromatography-high resolution mass spectrometry(2DLC-HRMS), and the impurity monomer was obtained by directional synthesis. The structure of the impurity was confirmed by 1H-NMR and 13C-NMR, chromatographic separations were performed on an Thermo Syncronis C18(250 mm×4.6 mm, 5 μm) column. Using 5 mmol·L-1 potassium dihydrogen phosphate buffer(pH 2.8) as mobile phase A, while methanol-acetonitrile(50:50) was mobile phase B, with gradient elution. The mobile phase was pumped at 1.0 mL·min-1. The column temperature was 30℃. The detection wavelength was 235 nm. RESULTS Nimodipine and its related substances had good separation. The correction factors of every impurities ranged from 0.8 to 1.1. CONCLUSION The established method has good specificity and can effectively isolate and determine the related substances in nimodipine oral solution. This study provides a reference to guide the impurity control of nimodipine oral solution and other dosage forms.

Abstract OBJECTIVE To develop an ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for determination of hynchophylline, isorhynchophylline, isocorynoxeine, corynoxeine, hirsutine and hirsuteine in Uncaria decoction, and investigate the effect of different storage conditions on the stability of active ingredients. METHODS An UHPLC-MS/MS method was established to investigate the effects of different storage temperature and time on the stability of six active components in Uncaria decoction. Separation was performed with a gradient mobile phase system of acetonitrile-0.1% formic water solution, the flow rate was 0.4 mL·min-1, the temperature of column was 30℃, the injection volume was 2 μL, the MS detection was dynamic multiple reaction monitoring mode. The effects of different storage temperature and time on the stability of six active components in Uncaria decoction was investigated. RESULTS Rhynchophylline, isorhynchophylline, corynoxeine, isocorynoxeine, hirsutine and hirsuteine were successfully separated using this method, with good linear relationship in the corresponding concentration range. The precision, repeatability, stability and recovery rate were good. The six alkaloids were basically stable within 14 d under low temperature storage, basically stable within 3 d under normal temperature storage, and not stable under high temperature storage. CONCLUSION The UHPLC-MS/MS method is stable, rapid and reproducible. It can be used to determine the contents of six effective components in Uncaria decoction. Cold storage is beneficial to the stability of Uncaria decoction.

Abstract OBJECTIVE To develop LC-MS method for the simultaneous determination of impurities A, C, and D of caspofungin acetate. METHODS Waters CORTECS® C18+(4.6 mm×150 mm, 2.7 μm) was used as the chromatography column. Mobile phase A and B were 0.1% formic acid-H2O and 0.1% formic acid-CH3CN, respectively. Electrospray ion source-single quadrupole mass spectrometry was used to detect impurities A and C in positive ion mode and impurity D in negative ion mode. RESULTS The correlation coefficient r was ≥ 0.999 in linearity ranges of impurities A, C and D. The average recoveries were 100.5%, 104.1% and 105.2%, respectively, with RSD<4%(n=6). The LOQs (S/N=10) of impurities A, C and D were 31.8, 6.99 and 15.5 ng·mL-1 respectively. The contents of impurities A, C and D in the three samples were all below the limits. CONCLUSION The developed LC-MS method is simple, sensitive, and applicable, which can be used to simultaneously determine impurities A, C and D in caspofungin acetate and can also provide a reference for the detection of other impurities in caspofungin acetate.