Potential Synergy Mechanism of Processing Methods for the Basic Remedies of Qixue Shuangbu Prescription Based on Integrated Metabolomics Strategy and Network Pharmacology Study

Abstract

Qixue Shuangbu Prescription (QSP) is a famous traditional Chinese medicine (TCM) formula widely used for the treatment of chronic heart failure (CHF). Previous clinical studies have found that the efficacy of processed QSP has been significantly enhanced in the treatment of CHF. However, the synergistic mechanisms of processed QSP to enhance the treatment of CHF are still unclear. Generally, the changes in clinical effects mainly result from the variations of inside chemical basis caused by the TCM processing procedure. In this study, we developed a network pharmacology-integrated metabolomics strategy to clarify the difference of the effective compounds between crude and processed QSP, and further explain the mechanism of processed QSP to produce a synergistic effects. As a result, 69 different compounds were successfully screened, identified, quantified and verified as the most potential marker compounds. These different chemical components may play an anti-CHF and enhance the therapeutic effect through 52 action pathways such as estrogen signaling pathway, ubiquitin mediated proteolysis, protein processing in endoplasmic reticulum, etc. This study revealed that the proposed network pharmacology-integrated metabolomics strategy was a powerful tool for explaining the mechanism of synergistic action in the processing of QSP, further controlling the quality and understanding the processing mechanism of TCM formulae.

Exploring the Efficacy Enhancement Mechanism of Qixue Shuangbu prescription after TCM processing for treating chronic heart failure by regulating ERK/Bcl-2/Bax/Caspases-3 signaling pathway

“…Nine crude Chinese medicine decoction pieces of QSP were supplied by the Affiliated Taizhou People's Hospital of Nanjing Medical University, and authenticated by Dr. Linwei Chen. The CQSP and PQSP were prepared according to our previous studies [ [15] , [16] , [17] ]. Benazepril hydrochloride tablet (BHT) was purchased from Beijing Novartis Pharmaceutical Co., Ltd (Beijing, China).…”

Synergistic mechanism of processing method for Qixue Shuangbu prescription in the treatment of chronic heart failure based on plasma metabolomics—Systematic bioinformatics

“…Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of the PPI network was analyzed by David database (https:// david.ncifcrf.gov/), which explains the role of the targets in signaling pathways. In order to obtain the primary role of QSP in pathway, we utilized Omicshare software (http://www.omicshare.com/) to perform the enrichment of visual processing results, and explored the mechanism of processed QSP to enhance the treatment of CHF [7].…”

“…These different chemical constituents may play an anti-CHF role and enhance the therapeutic effect through 52 action pathways such as estrogen signaling pathway, ubiquitin-mediated proteolysis, protein processing in endoplasmic reticulum, etc. [7]. We further studied the pharmacokinetics of seven bioactive constituents after oral administration of QSP in CHF pathological conditions [8].…”

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

“…TCM has unique advantages in treating complex clinical syndromes of CHF. The prestigious Qixue Shuangbu Prescription (QSP) is a TCM prescription from Professor Jingchun Meng based on his clinical experience in the treatment of cardiovascular diseases and has been used for decades in clinical [5, 6]. QSP is mainly composed of nine Chinese herbs, including Ginseng Radix et Rhizoma (GRR), Astragali Radix (AR), Angelicae Sinensis Radix (ASR), Paeoniae Radix Alba (PRA), Polygonati Rhizoma (PR), Polygonati Odorati Rhizoma (POR), Polygoni Multiflori Radix (PMR), Lycii Fructus (LF), and Citri Reticulatae Pericarpium (CRP).…”