Discovery of pulmonary fibrosis inhibitor targeting TGF-β RI in Polygonum cuspidatum by high resolution mass spectrometry with in silico strategy

Journal of Pharmaceutical AnalysisVolume 12, Issue 6, December 2022, Pages 860-868Journal of Pharmaceutical AnalysisAuthor links open overlay panelHighlights•

The LC-HR MS method allows the identification of the 24 chemical ingredients of Polygonum cuspidatum.

The present methods clarify the interactions between resveratrol and TGF-β RI.

Method to explore natural products with excellent biological activity toward specific therapeutic targets is innovative.

Abstract

Pulmonary fibrosis (PF) is an irreversible lung disease that is characterized by excessive scar tissue with a poor median survival rate of 2–3 years. The inhibition of transforming growth factor-β receptor type-I (TGF-β RI) by an appropriate drug may provide a promising strategy for the treatment of this disease. Polygonum cuspidatum (PC) is a well-known traditional Chinese herbal medicine which has an anti-PF effect. Accordingly, a combination of high resolution mass spectrometry with an in silico strategy was developed as a new method to search for potential chemical ingredients of PC that target the TGF-β RI. Based on this strategy, a total of 24 ingredients were identified. Then, absorption, distribution, metabolism, and excretion (ADME)-related properties were subsequently predicted to exclude compounds with potentially undesirable pharmacokinetics behaviour. Molecular docking studies on TGF-β RI were adopted to discover new PF inhibitors. Eventually, a compound that exists in PC known as resveratrol was proven to have excellent biological activity on TGF-β RI, with an IC50 of 2.211 μM in vitro. Furthermore, the complex formed through molecular docking was tested via molecular dynamics simulations, which revealed that resveratrol had strong interactions with residues of TGF-β RI. This study revealed that resveratrol has significant potential as a treatment for PF due to its ability to target TGF-β RI. In addition, this research demonstrated the exploration of natural products with excellent biological activities toward specific targets via high resolution mass spectrometry in combination with in silico technology is a promising strategy for the discovery of novel drugs.

Keywords

Polygonum cuspidatum

Pulmonary fibrosis

TGF-β receptor type-I

Resveratrol

High resolution mass spectrometry

Molecular docking

© 2022 The Authors. Published by Elsevier B.V. on behalf of Xi’an Jiaotong University.

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