Raw Arecae Semen, the seed of Areca catechu L., as well as Arecae Semen Tostum and Arecae semen carbonisata are traditionally processed by stir-baking for subsequent use in a variety of clinical applications. These three Arecae semen types, important Chinese herbal drugs, have been used in China and other Asian countries for thousands of years. In this study, the sensory technologies of a colorimeter and sensitive validated high-performance liquid chromatography with diode array detection were employed to discriminate raw Arecae semen and its processed drugs. The color parameters of the samples were determined by a colorimeter instrument CR-410. Moreover, the fingerprints of the four alkaloids of arecaidine, guvacine, arecoline and guvacoline were surveyed by high-performance liquid chromatography. Subsequently, Student's t test, the analysis of variance, fingerprint similarity analysis, hierarchical cluster analysis, principal component analysis, factor analysis and Pearson's correlation test were performed for final data analysis. The results obtained demonstrated a significant color change characteristic for components in raw Arecae semen and its processed drugs. Crude and processed Arecae semen could be determined based on colorimetry and high-performance liquid chromatography with a diode array detector coupled with chemometrics methods for a comprehensive quality evaluation.
Raw Moutan Cortex (RMC) and Processed Moutan Cortex (PMC) have a long history of use in China and other Asian countries. In this study, a rapid and accurate ultra‐high‐pressure liquid chromatography coupled with diode array detector (UHPLC–DAD) method was developed and validated for the simultaneous determination of nine absorbed compounds of RMC/PMC. After extraction by protein precipitation with methanol from plasma, the analytes were separated on an Acquity UPLC® BEH Shield RP18 column (2.1 × 100 mm, 1.7 μm, Waters, USA). Acetonitrile (A) and 0.1% (v/v) formic acid in water (B) were selected as the mobile phase to perform gradient elution. The linearity of nine analytes was >0.9915. The intra‐ and inter‐assay precision (RSD) values were within 11.18%, and accuracy ranged from 91.32 to 101.29%. Suitable stability, matrix effect and extraction recoveries were also obtained. The validated method was applied to compare the pharmacokinetics of RMC and PMC in Blood‐Heat and Hemorrhage Syndrome Model and normal rats. The results revealed that processing and the pathological state could influence the pharmacokinetic characteristics of compounds in RMC/PMC. The study willbe useful for further studies on pharmacokinetics and clinical application of raw and processed Moutan Cortex.
Background
Raw Moutan Cortex (RMC) has been used in China and other Asian countries for thousands of years. Its medical application is the treatment of cooling blood and promoting blood circulation. However, its therapeutic mechanism is still undefined.
Methods
In this study, the pharmacokinetics strategy that integrated network analysis was employed to explore the mechanism of RMC in blood-heat and blood stasis syndrome (BHS) model rats. Firstly, Ultra-High performance Liquid Chromatography coupled with Diode Array Detector (UHPLC-DAD) method was developed to determine nine absorbed compounds in rat serum in BHS and normal rats after oral administration of RMC extract respectively. Then the pharmacology network was established based on the relationship between nine compounds absorbed into the blood and BHS targets. Finally, the predicted hub targets were validated experimentally in human umbilical vein endothelial cells (HUVECs).
Results
Pharmacokinetic study showed that the pharmacokinetic parameters of nine absorbed compounds had significant differences between BHS and normal groups (p < 0.05). Network analysis showed that 8 target genes, namely, F2, F10, F7, PLAU, MAPK14, MAPK10, AKT1, and NOS3 may be the primary targets regulated by RMC for the treatment of BHS. Among them, targets (F2, F10, F7 and MAPK14, MAPK10, AKT) and 4 active ingredients (paeonol, paeoniflorin, quercetin and oxypaeoniflorin) were selected for evaluating the reliability in vitro experiments, which revealed that the mechanism of RMC against BHS syndrome may inhibit inflammatory pathways and regulate coagulation cascades pathway for cooling and promoting blood circulation.
Conclusion
The proposed pharmacokinetics study integrated network analysis strategy provides a combination method to explore the therapeutic mechanism of RMC on BHS.
Graphical Abstract
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