Effective substance and mechanism of Ziziphi Spinosae Semen extract in treatment of insomnia based on serum metabolomics and network pharmacology / 中国中药杂志

This study aims to study the effective substance and mechanism of Ziziphi Spinosae Semen extract in the treatment of insomnia based on serum metabolomics and network pharmacology. The rat insomnia model induced by p-chlorophenylalanine(PCPA) was established. After oral administration of Ziziphi Spinosae Semen extract, the general morphological observation, pentobarbital sodium-induced sleep test, and histopathological evaluation were carried out. The potential biomarkers of the extract in the treatment of insomnia were screened by ultra-high performance liquid chromatography-mass spectrometry(UHPLC-MS) combined with multivariate analysis, and the related metabolic pathways were further analyzed. The "component-target-pathway" network was constructed by ultra-high performance liquid chromatography coupled with quadrupole-Exactive mass spectrometry(UHPLC-Q-Exactive-MS/MS) combined with network pharmacology to explore the effective substances and mechanism of Ziziphi Spinosae Semen in the treatment of insomnia. The results of pentobarbital sodium-induced sleep test and histopathological evaluation(hematoxylin and eosin staining) showed that Ziziphi Spinosae Semen extract had good theraputic effect on insomnia. A total of 21 endogenous biomarkers of Ziziphi Spinosae Semen extract in the treatment of insomnia were screened out by serum metabolomics, and the metabolic pathways of phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, and nicotinate and nicotinamide metabolism were obtained. A total of 34 chemical constituents were identified by UHPLC-Q-Exactive-MS/MS, including 24 flavonoids, 2 triterpenoid saponins, 4 alkaloids, 2 triterpenoid acids, and 2 fatty acids. The network pharmacological analysis showed that Ziziphi Spinosae Semen mainly acted on target proteins such as dopamine D2 receptor(DRD2), 5-hydroxytryptamine receptor 1 A(HTR1 A), and alpha-2 A adrenergic receptor(ADRA2 A) in the treatment of insomnia. It was closely related to neuroactive ligand-receptor interaction, serotonergic synapse, and calcium signaling pathway. Magnoflorine, N-nornuciferine, caaverine, oleic acid, palmitic acid, coclaurine, betulinic acid, and ceanothic acid in Ziziphi Spinosae Semen may be potential effective compounds in the treatment of insomnia. This study revealed that Ziziphi Spinosae Semen extract treated insomnia through multiple metabolic pathways and the overall correction of metabolic disorder profile in a multi-component, multi-target, and multi-channel manner. Briefly, this study lays a foundation for further research on the mechanism of Ziziphi Spinosae Semen in treating insomnia and provides support for the development of innovative Chinese drugs for the treatment of insomnia.

Study on quality identification of Curcumae Rhizoma from different origins based on quantitative analysis of appearance color and content of main components / 中国中药杂志

L~*, a~* and b~* values of prepared slices of Curcumae Rhizoma were measured by spectrophotometer. SPSS 21.0 was used for discriminant analysis to establish the color range and mathematical prediction model of prepared slices of Curcumae Rhizoma. The values of L~*, a~* and b~* of kwangsiensis ranged from 58.09-62.40, 4.53-5.66 and 23.61-24.29, while the values of L~*, a~* and b~* of phaeocaulis were between 64.02-70.71,-0.89-4.13 and 44.59-54.52, respectively. The values of L~*, a~* and b~* of wenyujin were 68.55-70.99,-0.11-1.47 and 28.26-32.19, respectively. The mathematical prediction model was proved to be able to realize 100% identification of Curcumae Rhizome of different origins through original and cross validation and external samples validation. A dual wavelength HPLC was established; the contents of 9 sesquiterpenoids and 3 Curcumae Rhizomes were determined simultaneously; and the contents of Curcumae Rhizome of different origins were determined. The results showed that kwangsiensis had higher contents of neocurdione, β-elemene and isocurcumaenol, phaeocaulis curcumin, furadienone, demethoxycurcumin and curcumin; and wenyujin mainly contained curdione, furadienes and guimarone. Pearson correlation analysis on L~*, a~*, b~* value and content of 12 components showed that curcumin, furadienone, demethoxycurcumin and curcumin had a significant positive correlation with b~* value(P<0.01). There was a significant negative correlation between neocurdione, β-elemene and isocurcumaenol and L~* value(P<0.01). Curdione, furadienes and guimarone were significantly correlated with L~* value(P<0.01),indicating that the appearance co-lor of Curcumae Rhizoma could reflect the change of the content of the internal components. This study provided reference for the rapid recognition of Curcumae Rhizoma and the establishment of quality evaluation system.

Network pharmacology study on potential active components in volatile oil of Dictamni Cortex / 中国中药杂志

There are many chemical components in the volatile oil of Dictamni Cortex. The complex network relationship of "component-target-disease" can be revealed by using the network pharmacology method, and the mechanism of the efficacy of Dictamni Cortex can be revealed. In this study, we used Swiss Target Prediction database to predict the target of action, STRING database to build protein interaction network, and Cytoscape software to build "component-target-disease" network. The results showed that the antibacterial, anti-inflammatory and antiallergic effects of Dictamni Cortex were closely related to the components of thymol methyl ether, elemenol, anethole, and the related targets of each component were cross-linked to play a multi-target pharmacodynamic role. This study laid a foundation for the study of the effective substance basis and quality control evaluation of the Dictamni Cortex, and provided a scientific basis for further revealing its mechanism.