Analysis of Chemical Variability on Different Processed Products of Glycyrrhiza uralensis Dry Roots and Rhizomes Based on UPLC-Q-TOF-MSE and Plant Metabolomics / 中国实验方剂学杂志

Objective:To identify the quality differential markers of different processed products of Glycyrrhiza uralensis dry roots and rhizomes. Method:Ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MSE) was used to collect high-precision mass-charge ratio and ion response strength information of the components in G. uralensis dry roots and rhizomes before and after processing by negative ion mode. The data set collected after pretreatment was analyzed with principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) to quickly search the differential components in different processed products of G. uralensis dry roots and rhizomes. Differential components were identified according to the relative molecular weight, fragment ion, mass spectrum database and related literature information, then the migration of components before and after processing was studied. Result:A total of 10 quality differential markers were searched from raw products, roasted products and honey-roasted products of G. uralensis dry roots and rhizomes, mainly derivatives of liquiritin and glycyrrhizic acid. Among them, the contents of 6''-O-acetylliquiritin apioside, 6''-O-acetylliquiritin apioside isomer, 6''-O-acetylliquiritin, formononetin and 11-deoxo-18β-glycyrrhetic acid were the highest in the raw products, the contents of 6''-O-acetylisoliquiritin apioside, 6''-O-acetylisoliquiritin, isoliquiritin and glycyrrhetic acid 3-O-glucuronide were the highest in the roasted products, the content of liquiritin was the lowest in the honey-roasted products. 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 G. uralensis dry roots and rhizomes.

Discussion on Research and Development of Following Original Methods of Famous Classical Formulas——Taking Xiebaisan as an Example / 中国实验方剂学杂志

The National Medical Products Administration intends to simplify the registration and approval process of the classic Chinese herbal compound preparations that meet the requirements, but it is a prerequisite for obtaining preferential policies that the preparation method and the route of administration are consistent with the records of ancient medical books. As most of the famous classical formulas are recorded in the medical books of the Qing dynasty and before the Qing dynasty, during the use of medicinal materials in various dynasties, the processing of herbs, dose of medicinal herbs, and the method of decocting may have changed. If researchers simply adopt modern methods to study the formula, it is easy to deviate from policy requirements. The strengthening of preliminary data survey and definition of prescription component and the medication situation of the dynasties can provide strong theoretical support for the study of famous classical formulas. Based on this, the authors take Xiebaisan as an example, which being collected in the First Batch of Catalogue of Ancient Classical Formulas. By following the principles of ancient methods, the research and development ideas of the classic Chinese herbal compound preparations were expounded from the aspects of origin of medicinal materials, processing of medicinal materials, preparation of standard decoction and quality standard of Xiebaisan granules, so as to provide a referential method for the development and research of the famous classical formulas.

Effect of salvianolic acid B by intranasal administration on cognitive function and neurogenesis of cerebral ischemia rats / 中草药

Objective: To study the concentration of salvianolic acid B (Sal B) in rat hippocampus after intranasal administration, and to inveategate the improvement on cognitive dysfunction of rats with cerebral ischemic treated by intranasal administration of Sal B and its mechnisms. Methods: HPLC method was employed to check the distribution of Sal B in hippocampus by intranasal administration. Sal B was intranasal administered after one week of cerebral ischemia. The effect of Sal B by intranasal administration on cognitive dysfuctiopn was checked using Morris water maze. The effect of Sal B by intranasal administration on the hippocampus morphological characteristics was studied using Cresyl violet (Nissl) staining. BrdU injection and immunohistochemical staining were used to test the effect of Sal B on the neurogensis in hippocampus of cerebral ischemic rats. Results: After intranasal administration of Sal B, the Cmax of Sal B was (2.47 ± 0.55) μg/g, and the AUC of Sal B was (336.4 ± 73.0) μg∙min/g. Morris water maze test results showed that Sal B by intranasal administration could reduce the average escape latency of cerebral ischemic rats, increase the time in the former platform quadrant and the time of rats across the platform. Compared with the Sham group, the hippocampal CA1 cell layers were reduced and the pyramidal cells showed an irregular arrangement in the model group. Compared with model group, hippocampal morphology was clear, nerve cells arranged in regular, and the number of neurons increased significantly in groups of Sal B by intranasal administration. Immunohistochemistry results showed that the groups of Sal B by intranasal administration could increase the BrdU-positive cell number in hippocampus. Conclusion: Intranasal administration of SalB can significantly improve the distribution in the hippocampus. Intranasal administration of Sal B could improve the cognitive dysfuction, and this effect maybe related to the directive effect of Sal B on promoting neurogenesis after cerebral ischemic.

Influence of ultrafiltration membrane on ophiopogonins and homoisoflavonoids in Ophiopogon japonicus as measured by ultra-fast liquid chromatography coupled with ion trap time-of-flight mass spectrometry / 中国天然药物

Ultrafiltration is one of the most fascinating technologies, which makes it possible to improve the quality of traditional medicines for application in the pharmaceutical industry. However, researchers have paid little attention to the effect of ultrafiltration membrane on traditional medicines chemical constituents. In this work, Ophiopogon japonicus (L.f) Ker-Gawl. was used as an example to illuminate the influence of ultrafiltration with different material and molecular weight cut-off (MWCO) membrane on natural chemical constituents as measured by ultra-fast liquid chromatography coupled with ion trap time-of-flight mass spectrometry (UFLC-IT-TOF/MS). Our results indicated that ultrafiltration membrane significantly impacted homoisoflavonoids, especially homoisoflavonoids that were almost completely retained on the polyethersulfone (PES) membrane. We also found that the larger number of aglycone hydroxy and sugar moiety in steroid saponins, the higher the transmittance. Furthermore, the passage rate (%) of ophiogenin type saponins was higher than that of others. The possible adsorptive mechanisms were hydrogen bonding, hydrophobic interactions, and benzene ring interaction by π-π stacking. In conclusion, it is crucial to choose appropriate ultrafiltration membrane based on the characteristics of produce products for application of ultrafiltration technique.

Protective effect of the extract of Yi-Qi-Fu-Mai preparation on hypoxia-induced heart injury in mice / 中国天然药物

Yi-Qi-Fu-Mai (YQFM) is extensively used clinically to treat cardiovascular diseases in China. To explore the anti-hypoxia effect of the extract of YQFM preparation (EYQFM), the EYQFM (1.4, 2.8, and 5.5 g·kg(-1)·d(-1)) was assessed for its heart-protective effect in a chronic intermittent hypoxia (CIH) animal model (oxygen pressure 7%-8%, 20 min per day) for 28 days of treatment. Betaloc (0.151 6 g·kg(-1)·d(-1)) was used as a positive control. The histopathological analyses of heart in CIH mice were conducted. Several cardiac state parameters, such as left ventricular ejection fractions (EF), stroke volume (SV), expression of creatine kinase (CK), lactate dehydrogenase (LDH), superoxide dismutase (SOD), and malondialdehyde (MDA) were measured. The results showed that treatment with EYQFM markedly reversed swelling of the endothelial cells and vacuolization in the heart when compared with the model group. Further study demonstrated that EYQFM significantly improved ventricular myocardial contractility by increasing EF and SV. In addition, EYQFM inhibited the activity of CK, LDH, decreased the level of MDA and improved SOD activity. The results demonstrated that EYQFM significantly improved the tolerability of myocardium to hypoxia and ameliorated the cardiac damage in the CIH model.

Monitoring method for macroporous resin column chromatography process of salvianolic acids based on near infrared spectroscopy / 中国中药杂志

To study and establish a monitoring method for macroporous resin column chromatography process of salvianolic acids by using near infrared spectroscopy (NIR) as a process analytical technology (PAT).The multivariate statistical process control (MSPC) model was developed based on 7 normal operation batches, and 2 test batches (including one normal operation batch and one abnormal operation batch) were used to verify the monitoring performance of this model. The results showed that MSPC model had a good monitoring ability for the column chromatography process. Meanwhile, NIR quantitative calibration model was established for three key quality indexes (rosmarinic acid, lithospermic acid and salvianolic acid B) by using partial least squares (PLS) algorithm. The verification results demonstrated that this model had satisfactory prediction performance. The combined application of the above two models could effectively achieve real-time monitoring for macroporous resin column chromatography process of salvianolic acids, and can be used to conduct on-line analysis of key quality indexes. This established process monitoring method could provide reference for the development of process analytical technology for traditional Chinese medicines manufacturing.

Construction of NIRS-based process analytical system for production of salvianolic acid for injection and relative discussion / 中国中药杂志

Currently, near infrared spectroscopy (NIRS) has been considered as an efficient tool for achieving process analytical technology(PAT) in the manufacture of traditional Chinese medicine (TCM) products. In this article, the NIRS based process analytical system for the production of salvianolic acid for injection was introduced. The design of the process analytical system was described in detail, including the selection of monitored processes and testing mode, and potential risks that should be avoided. Moreover, the development of relative technologies was also presented, which contained the establishment of the monitoring methods for the elution of polyamide resin and macroporous resin chromatography processes, as well as the rapid analysis method for finished products. Based on author's experience of research and work, several issues in the application of NIRS to the process monitoring and control in TCM production were then raised, and some potential solutions were also discussed. The issues include building the technical team for process analytical system, the design of the process analytical system in the manufacture of TCM products, standardization of the NIRS-based analytical methods, and improving the management of process analytical system. Finally, the prospect for the application of NIRS in the TCM industry was put forward.