Comparative pharmacokinetics of 11 major bioactive components between two dosage forms of Qixue Shuangbu Prescription in rats by ultra-high-performance liquid chromatography-tandem mass spectrometry.

Although Qixue Shuangbu Prescription (QSP) is a classic Chinese medicine prescription for treating chronic heart failure. Low bioavailability due to the insolubility and poor biofilm permeability of the main bioactive ingredients of QSP is still a key factor limiting its efficacy. In this study, a novel self-microemulsifying drug delivery system was proposed to effectively improve the bioavailability of QSP. The qualified ultra-high-performance liquid chromatography-tandem mass spectrometry methodology was established to investigate the pharmacokinetics characteristics of the QSP self-microemulsifying drug delivery system. Our results showed that 11 components in the self-microemulsifying drug delivery system group had prolonged T1/2 and MRT0-t values compared with QSP extract. The Cmax of calycosin-7-glucoside (CG), vanillic acid and paeoniflorin increased 2.5 times, 2.4 times and 2.3 times, respectively. The relative bioavailability values of CG, paeoniflorin and ononin were most significantly affected, increasing by 383.2%, 336.5% and 307.1%, respectively. This study promoted the development of new dosage forms of QSP and provided a useful reference for improving dosage forms to solve the problem of low bioavailability of traditional Chinese medicine.

Comparative pharmacokinetics of four bioactive components in normal and chronic heart failure rats after oral administration of Qiangxin Lishui Prescription by microdialysis combined with ultra-high-performance liquid chromatography.

Qiangxin Lishui Prescription (QLP) has been clinically applied for treating heart failure with remarkable curative effects. A multi-component pharmacokinetic research is very necessary for determining active substances in it. This study aims to profile the traits and differences in the pharmacokinetics of salvianolic acid B, astragaloside IV, calycosin-7-O-ß-D-glucoside and kaempferol in QLP between normal and chronic heart failure (CHF) rats by microdialysis combined with ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Sensitive, selective, and online microdialysis combined with the UHPLC-MS/MS method was successfully established and applied to study the pharmacokinetics of QLP. The pathological condition of CHF could lead to the enhancement of systematic exposure and reduction of the metabolic rate of four bioactive components for better bioavailability and therapeutic efficacy. The pharmacokinetic results will provide data support for the clinical application of QLP.

Identification and quality evaluation of different processed products of Aconitum carmichaelii by ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry and ultra-high-performance liquid chromatography-tandem mass spectrometry.

Aconitum carmichaelii is widely used to treat chronic and intractable diseases due to its remarkable curative effect, but it is also a highly toxic herb with severe cardiac and neurotoxicity. It has been combined with honey for thousands of years to reduce toxicity and enhance efficacy, but there has been no study on the chemical constituent changes in the honey-processing so far. In this study, the chemical constituents of A. carmichaelii before and after honey-processing were characterized by ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry. The results showed that a total of 118 compounds were identified, of which six compounds disappeared and five compounds were newly produced after honey-processing, and the cleavage pathway of main components was elucidated. At the same time, 25 compounds were found to have significant effects on different products, among which four compounds with the biggest difference were selected for quantitative analysis by ultra-high-performance liquid chromatography-tandem mass spectrometry. This study not only explained the chemical differences between the different products, but also helped to control the quality of the honey-processed products more effectively, and laid a foundation for further elucidating the mechanism of chemical constituent change during the honey-processing of A. carmichaelii.

Comparative pharmacokinetics of seven bioactive components after oral administration of crude and processed Qixue Shuangbu Prescription in chronic heart failure rats by microdialysis combined with UPLC-MS/MS.

ETHNOPHARMACOLOGICAL RELEVANCE: Qixue Shuangbu Prescription (QSP) is a classical traditional Chinese medicine prescription, which has widely used for the treatment of chronic heart failure (CHF). Preliminary clinical studies have shown that the efficacy of processed QSP (P-QSP) in treating CHF is greater than crude QSP (C-QSP). However, the pharmacokinetic characteristics of its major bioactive components under pathological conditions are unclear. AIM OF STUDY: This study aims to compare pharmacokinetics of seven bioactive components after oral administration of C-QSP and P-QSP in CHF model rats. MATERIALS AND METHODS: Ginsenoside Rb1, ginsenoside Re, ginsenoside Rg1, ferulic acid, astragaloside IV, calycosin-7-O-ß-D-glucoside, and paeoniflorin in QSP were used as the target components. CHF model in rats was induced by the intraperitoneal injection of doxorubicin. A microdialysis combined with UPLC-MS/MS method was first established to compare the pharmacokinetics of seven major bioactive components in CHF model rats after oral administration of C-QSP and P-QSP. RESULTS: This method was successfully applied to the pharmacokinetic investigation of seven major components of C-QSP and P-QSP following oral administration in CHF model rats. Compared with the C-QSP group, the Cmax, AUC0-t and AUC0-∞ of ginsenoside Rb1, ginsenoside Re, ginsenoside Rg1, ferulic acid, astragaloside IV and paeoniflorin significantly increased (P < 0.05) in the P-QSP group, which suggested that the absorptivity and bioavailability were increased. Lower T1/2, MRT0-t of ginsenoside Rb1, gerulic acid and higher T1/2, MRT0-t of ginsenoside Rb1, astragaloside IV, paeoniflorin in the P-QSP group, which indicated that eliminated more quickly or slowly, respectively. CONCLUSIONS: The pharmacokinetic parameters of bioactive components were significantly changed for better bioavailability and absorption, longer lasting time elimination, which were beneficial for enhancing therapeutic efficacy in the P-QSP group. This study will provide a new perspective to explain the pharmacokinetic-pharmacodynamic correlation of P-QSP on the treatment of CHF.

Elucidation of the Mechanisms and Molecular Targets of Sanhuang Xiexin Decoction for Type 2 Diabetes Mellitus Based on Network Pharmacology.

Sanhuang Xiexin Decoction (SXD) is commonly used to treat type 2 diabetes mellitus (T2DM) in clinical practice of traditional Chinese medicine (TCM). In order to elucidate the specific analysis mechanisms of SXD for T2DM, the method of network pharmacology was applied to this article. First, the effective ingredients of SXD were obtained and their targets were identified based on the TCMSP database. The T2DM-related targets screened from the GEO database were also collected by comparing the differential expressed genes between T2DM patients and healthy individuals. Then, the common targets in SXD-treated T2DM were obtained by intersecting the putative targets of SXD and the differential expressed genes of T2DM. And the protein-protein interaction (PPI) network was established using the above common targets to screen key genes through protein interactions. Meanwhile, these common targets were used for GO and KEGG analyses to further elucidate how they exert antidiabetic effects. Finally, a gene pathway network was established to capture the core one in common targets enriched in the major pathways to further illustrate the role of specific genes. Based on the data obtained, a total of 67 active compounds and 906 targets of SXD were identified. Four thousand one hundred and seventy-six differentially expressed genes with a P value < 0.005 and ∣log2(fold change) | >0.5 were determined between T2DM patients and control groups. After further screening, thirty-seven common targets related to T2DM in SXD were finally identified. Through protein interactions, the top 5 genes (YWHAZ, HNRNPA1, HSPA8, HSP90AA1, and HSPA5) were identified. It was found that the functional annotations of target genes were associated with oxygen levels, protein kinase regulator, mitochondria, and so on. The top 20 pathways including the PI3K-Akt signaling pathway, cancers, HIF-1 signaling pathway, and JAK-STAT signaling pathway were significantly enriched. CDKN1A was shown to be the core gene in the gene-pathway network, and other several genes such as CCND1, ERBB2, RAF1, EGF, and VEGFA were the key genes for SXD against T2DM. Based on the network pharmacology approach, we identified key genes and pathways related to the prognosis and pathogenesis of T2DM and also provided a feasible method for further studying the chemical basis and pharmacology of SXD.