Deciphering metabonomics biomarkers-targets interactions for psoriasis vulgaris by network pharmacology

Abstract

Objectives: Psoriasis vulgaris is a chronic inflammatory and immune-mediated skin disease. 44 metabonomics biomarkers were identified by high-throughput liquid chromatography coupled to mass spectrometry in our previous work, but the roles of metabonomics biomarkers in the pathogenesis of psoriasis is unclear.

Methods: The metabonomics biomarker-enzyme network was constructed. The key metabonomics biomarkers and enzymes were screened out by network analysis. The binding affinity between each metabonomics biomarker and target was calculated by molecular docking. A binding energy-weighted polypharmacological index was introduced to evaluate the importance of target-related pathways.

Results: Long-chain fatty acids, phospholipids, Estradiol and NADH were the most important metabonomics biomarkers. Most key enzymes belonged hydrolase, thioesterase and acyltransferase. Six proteins (TNF-alpha, MAPK3, iNOS, eNOS, COX2 and mTOR) were extensively involved in inflammatory reaction, immune response and cell proliferation, and might be drug targets for psoriasis. PI3K-Akt signaling pathway and five other pathways had close correlation with the pathogenesis of psoriasis and could deserve further research.

Conclusions: The inflammatory reaction, immune response and cell proliferation are mainly involved in psoriasis. Network pharmacology provide a new insight into the relationships between metabonomics biomarkers and the pathogenesis of psoriasis.

KEY MESSAGES

•   • Network pharmacology was adopted to identify key metabonomics biomarkers and enzymes.

•   • Six proteins were screened out as important drug targets for psoriasis.

•   • A binding energy-weighted polypharmacological index was introduced to evaluate the importance of target-related pathways.

Keywords:

• Metabonomics biomarker
• psoriasis
• network pharmacology
• drug-target network
• binding energy-weighted polypharmacological index

Disclosure statement

The authors report no conflicts of interest.

Supplementary data

Supplementary Table S1, Supplementary S2 and Supplementary S3 are the target protein lists for inflammatory reaction, immune response and cell proliferation. Supplementary Table S4 is the information of enzymes for MBs. Supplementary Table S5 is the binding energy between metabonomics biomarker and target calculated by AutoDock.

Additional information

Funding

This work was supported by the National Key Technology R&D Program for the 12th Five-year Plan of Ministry of Science and Technology, China [2013BAI02B03]; Team project of Natural Science Foundation of Guangdong Province [S2013030011515]; Guangdong Science and Technology project [2016A020226010, 2017A020213011]; Special research on Chinese Medical Science and Technology of Guangdong Provincial Hospital of Chinese Medicine [YN2016MJ06]; The start-up support for scientific research of Xinglin Yong Scholar in Guangzhou University of Chinese Medicine [A1-AFD018161Z04]. The calculations were performed on high-performance computer cluster of Guangdong Provincial Hospital of Traditional Chinese Medicine.