Network pharmacology combined with metabolomics approach to investigate the protective role and detoxification mechanism of Yunnan Baiyao formulation

Jun-Ling Ren; Hui Dong; Ying Han; Le Yang; Ai-Hua Zhang; Hui Sun; Yue Li; Guangli Yan; Xi-Jun Wang

doi:10.1016/j.phymed.2020.153266

Network pharmacology combined with metabolomics approach to investigate the protective role and detoxification mechanism of Yunnan Baiyao formulation

Phytomedicine. 2020 Oct:77:153266. doi: 10.1016/j.phymed.2020.153266. Epub 2020 Jun 14.

Authors

Jun-Ling Ren¹, Hui Dong¹, Ying Han¹, Le Yang¹, Ai-Hua Zhang¹, Hui Sun¹, Yue Li¹, Guangli Yan¹, Xi-Jun Wang²

Affiliations

¹ National Chinmedomics Research Center, Sino-America Chinmedomics Technology Collaboration Center, National TCM Key Laboratory of Serum Pharmacochemistry, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin 150040, China.
² National Chinmedomics Research Center, Sino-America Chinmedomics Technology Collaboration Center, National TCM Key Laboratory of Serum Pharmacochemistry, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin 150040, China. Electronic address: xijunw@sina.com.

PMID: 32629383
DOI: 10.1016/j.phymed.2020.153266

Abstract

Background: Yunnan Baiyao (YNBY) is a traditional Chinese medicine formulae, which has the functions of hemostasis, activating blood circulation and removing blood stasis, anti-inflammation, etc. Although the presence of Caowu (CW, Aconiti Kusnezoffii Radix), the detoxification mechanism of YNBY is still unclear.

Purpose: In current study, network pharmacology, toxicological methods and metabolomics technique were applied to explore YNBY in attenuating toxicity of CW.

Methods: Prediction of targets and pathways of CW were carried out by commonly used network pharmacological method. Simultaneously, SD rats were orally administrated with CW, processed CW (ZCW), YNBY, and YNBY which lack of CW (QCW) for 15 days. Tissue samples were observed with histopathology. Urine samples were analyzed with ultra-performance liquid chromatography-mass spectrometry to screen differential metabolites and related metabolic pathways associated with toxicity of CW. Furthermore, by comparing the changes of the metabolite contents, focused the attenuated metabolic pathway. Finally, the network pharmacological and experimental data were integrated to investigate detoxification mechanism of YNBY.

Results: A total of 44 potential toxicity biomarkers were identified and 14 related pathways were involved in the toxicity of CW. Furthermore, 5 core toxicity biomarkers (2-keto-6-acetamidocaproate, γ-glutamylleucine, prostaglandin E₃, 4-hydroxy-5-(3'-hydroxyphenyl)-valeric acid-3'-O-sulphate, and 3,4-dihydroxy- phenylglycol O-sulfate) were regulated to normal condition in YNBY group. Lysine degradation was locked as the core metabolic pathway of detoxification of YNBY. Integrating the predicted results of network pharmacology, ACHE, SLC6A3, SLC6A4 might be the target of protective role of other herbs in YNBY.

Conclusion: Network pharmacology combined with metabolomics exhibited a powerful mean to investigate the herbal toxicity and probed into the detoxification mechanism of formulae, which contributes to its safety evaluation.

Keywords: Detoxification; Metabolism; Metabolomics; Network pharmacology; Toxicity.

MeSH terms

Aconitum / chemistry
Animals
Biomarkers / analysis
Biomarkers / metabolism
China
Drugs, Chinese Herbal / pharmacokinetics
Drugs, Chinese Herbal / pharmacology*
Drugs, Chinese Herbal / toxicity
Gene Expression Regulation / drug effects
Inactivation, Metabolic
Lysine / metabolism
Male
Mass Spectrometry / methods
Metabolic Networks and Pathways / drug effects*
Metabolomics / methods
Protective Agents / pharmacology*
Rats, Sprague-Dawley

Substances

Biomarkers
Drugs, Chinese Herbal
Protective Agents
yunnan baiyao
Lysine