Network Pharmacology and Bioactive Equivalence Assessment Integrated Strategy Driven Q-markers Discovery for Da-Cheng-Qi Decoction to Attenuate Intestinal Obstruction.

Abstract

BACKGROUND:

Intestinal obstruction (IO) is a kind of acute abdomen with high morbidity and mortality. Patients suffer from poor quality of life and tremendous financial pressure. Da-Cheng-Qi decoction (DCQD), a classical purgation prescription, has clinically been proven to be an effective treatment for IO.

PURPOSE:

Network pharmacology integrated with bioactive equivalence assessment was used to discover the quality marker (Q-marker) of DCQD against IO.

METHODS:

As there is hardly any targets recorded in database, thus the collection of IO targets was conducted by searching those of alternative diseases which have similar pathological symptoms with IO. In order to improve the reliability of the obtained targets, IO metabolomics data was introduced. Active compounds combination (ACC) was focused as potential Q-markers via component-target network analysis and function query from the identified components corresponding to the common targets. Bioequivalence between ACC and DCQD was assessed from the aspects of intestine motility (somatostatin secretion), inflammation (IL-6 secretion) and injury (wound healing assay) in vitro and was further validated in ileus rat model. PPI network analysis of core targets followed by gene pedigree classification and experimental validation confirmed the potential intervention pathway.

RESULTS:

A combination of 11 ingredients, including emodin, physcion, aloe-emodin, rhein, chrysophanol, gallic acid, magnolol, honokiol, naringenin, tangeretin, and nobiletin was finally confirmed bioequivalence with DQCD to some extent and could serve as Q-markers for DCQD to attenuate IO. PI3K/AKT was verified as a possible affected pathway that DCQD exerted the effectiveness against IO.

CONCLUSION:

For the disease with few recorded targets, searching those of alternative diseases which have similar pathological symptoms could be a feasible and effective approach. The proposed network pharmacology integrated bioactive equivalence evaluation paradigm is efficient to discover Q-marker of herbal formulae.

• Authors: Danting Li, Bo Lv, Di Wang, Doudou Xu, Siyuan Qin, Ying Zhang, Jie Chen, Wei Zhang, Zunjian Zhang, Fengguo Xu
• Journal: Phytomedicine : international journal of phytotherapy and phytopharmacology (Phytomedicine) Vol. 72 Pg. 153236 (Jul 2020) ISSN: 1618-095X [Electronic] Germany
• PMID: 32464544 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier GmbH. All rights reserved.

Chemical References

• Anthraquinones
• Biomarkers, Pharmacological
• Biphenyl Compounds
• Da-Cheng-Qi
• Drugs, Chinese Herbal
• Flavanones
• Lignans
• magnolol
• honokiol
• aloe emodin
• naringenin
• chrysophanic acid
• rhein

Topics

• Algorithms
• Animals
• Anthraquinones (analysis, pharmacokinetics)
• Biomarkers, Pharmacological (analysis)
• Biphenyl Compounds (analysis, pharmacokinetics)
• Data Mining
• Drugs, Chinese Herbal (chemistry, pharmacokinetics)
• Flavanones (analysis, pharmacokinetics)
• HT29 Cells
• Humans
• Intestinal Obstruction (drug therapy)
• Lignans (analysis, pharmacokinetics)
• Male
• Phosphatidylinositol 3-Kinases (metabolism)
• Rats, Sprague-Dawley
• Reproducibility of Results
• Therapeutic Equivalency