DanQi Pill Protects Against Heart Failure Through the Arachidonic Acid Metabolism Pathway by Attenuating Different Cyclooxygenases and Leukotrienes B4

Overview

Journal BMC Complement Altern Med

Publisher Biomed Central

Specialty Rehabilitation Medicine

Date 2014 Feb 22

PMID 24555740

Citations 22

Authors

Yong Wang

Chun Li

Zhongyang Liu

Tianjiao Shi

Qiyan Wang

Dong Li

Yan Wu

Jing Han

Shuzhen Guo

Binghua Tang

Wei Wang

Affiliations

Soon will be listed here.

Abstract

Background: Chinese herbal formulae are composed of complex components and produce comprehensive pharmacological effects. Unlike chemical drugs that have only one clear single target, the components of Chinese herbal formulae have multiple channels and targets. How to discover the pharmacological targets of Chinese herbal formulae and their underlying molecular mechanism are still under investigation.

Methods: DanQi pill (DQP), which is one of the widely prescribed traditional Chinese medicines, is applied as an example drug. In this study, we used the drug target prediction model (DrugCIPHER-CS) to examine the underlying molecular mechanism of DQP, followed by experimental validation.

Results: A novel therapeutic effect pattern of DQP was identified. After determining the compounds in DQP, we used DrugCIPHER-CS to predict their potential targets. These potential targets were significantly enriched in well-known cardiovascular disease-related pathways. For example, the biological processes of neuroactive ligand-receptor interaction, calcium-signaling pathway, and aminoacyl-tRNA biosynthesis were involved. A new and significant pathway, arachidonic acid (AA) metabolism, was also identified in this study. This predicted pathway alteration was validated with an animal model of heart failure (HF). Results show that DQP had effect both on thromboxane B2 (TXB2) and Prostaglandin I2 (PGI2) in different patterns. It can down-regulate the TXB2 and up-regulate the PGI2 in diverse way. Remarkably, it also had effect on cyclooxygenase (COX)-1 and COX2 by suppressing their levels, which may be the critical and novel mechanism of cardiacprotective efficacy for DQP. Furthermore, leukotrienes B4 (LTB4) receptor, another key molecule of AA metabolism which finally mediated gastrotoxic leukotrienes, was also reduced by DQP.

Conclusions: The combination of drug target prediction and experimental validation provides new insights into the complicated mechanism of DQP.

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