Molecular docking and network connections of active compounds from the classical herbal formula Ding Chuan Tang.

Allison Clyne,Ming Yang,Liping Yang,Brian May,Angela Wei Hong Yang

doi:10.7717/peerj.8685

Abstract

BackgroundDing Chuan Tang (DCT), a traditional Chinese herbal formula, has been consistently prescribed for the therapeutic management of wheezing and asthma-related indications since the Song Dynasty (960–1279 AD). This study aimed to identify molecular network pharmacology connections to understand the biological asthma-linked mechanisms of action of DCT and potentially identify novel avenues for asthma drug development.MethodsEmploying molecular docking (AutoDock Vina) and computational analysis (Cytoscape 3.6.0) strategies for DCT compounds permitted examination of docking connections for proteins that were targets of DCT compounds and asthma genes. These identified protein targets were further analyzed to establish and interpret network connections associated with asthma disease pathways.ResultsA total of 396 DCT compounds and 234 asthma genes were identified through database search. Computational molecular docking of DCT compounds identified five proteins (ESR1, KDR, LTA4H, PDE4D and PPARG) mutually targeted by asthma genes and DCT compounds and 155 docking connections associated with cellular pathways involved in the biological mechanisms of asthma.ConclusionsDCT compounds directly target biological pathways connected with the pathogenesis of asthma including inflammatory and metabolic signaling pathways.

Highlights

Asthma is defined and classified by its major physical characteristics including airflow obstruction and airway inflammation
Historical Chinese medical texts have documented the use of the traditional Chinese herbal formula Ding Chuan Tang (DCT), known as the Arrest Wheezing Decoction, for the use of asthma-like symptoms such as wheeze and cough since the Song dynasty (960–1279 AD) and the formulation in contemporary use, has been prescribed continually since the Ming Dynasty (1368–1644) (Hoizey & Hoizey, 1993)
Pharmacophore screening with DCT-compounds The virtual screening of the 396 DCT-compounds with the 117,423 pharmacophore models within the PharmaDB resulted in 159 pharmacophore models

Summary

Introduction

Asthma is defined and classified by its major physical characteristics including airflow obstruction and airway inflammation. Molecular docking and network connections of active compounds from the classical herbal formula Ding Chuan Tang. Methods: Employing molecular docking (AutoDock Vina) and computational analysis (Cytoscape 3.6.0) strategies for DCT compounds permitted examination of docking connections for proteins that were targets of DCT compounds and asthma genes. These identified protein targets were further analyzed to establish and interpret network connections associated with asthma disease pathways. Computational molecular docking of DCT compounds identified five proteins (ESR1, KDR, LTA4H, PDE4D and PPARG) mutually targeted by asthma genes and DCT compounds and 155 docking connections associated with cellular pathways involved in the biological mechanisms of asthma. Conclusions: DCT compounds directly target biological pathways connected with the pathogenesis of asthma including inflammatory and metabolic signaling pathways

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