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Exploration of the molecular mechanism of tea polyphenols against pulmonary hypertension by integrative approach of network pharmacology, molecular docking, and experimental verification

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Abstract

Pulmonary hypertension, a common complication of chronic obstructive pulmonary disease, is a major global health concern. Green tea is a popular beverage that is consumed all over the world. Green tea’s active ingredients are epicatechin derivatives, also known as “polyphenols,” which have anti-carcinogenic, anti-inflammatory, and antioxidant properties. This study aimed to explore the possible mechanism of green tea polyphenols in the treatment of pulmonary hypertension using network pharmacology, molecular docking, and experimental verification. A total of 316 potential green tea polyphenols-related targets were obtained from the PharmMapper, SwissTargetPrediction, and TargetNet databases. A total of 410 pulmonary hypertension-related targets were predicted by the CTD, DisGeNET, pharmkb, and GeneCards databases. Green tea polyphenols-related targets were hit by the 49 targets associated with pulmonary hypertension. AKT1 and HIF1-α were identified through the FDA drugs-target network and PPI network combined with GO functional annotation and KEGG pathway enrichment. Molecular docking results showed that green tea polyphenols had strong binding abilities to AKT1 and HIF1-α. In vitro experiments showed that green tea polyphenols inhibited the proliferation and migration of hypoxia stimulated pulmonary artery smooth muscle cells by decreasing AKT1 phosphorylation and downregulating HIF1α expression. Collectively, green tea polyphenols are promising phytochemicals against pulmonary hypertension.

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Funding

The authors gratefully acknowledge the Natural Science Foundation of Hunan Province, China (Grant Number: 2022JJ70013) and Hunan province inclusive policy and innovation environment construction plan—Clinical medical technology innovation guidance project (Grant Number: 2020SK50904).

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Authors and Affiliations

  1. Department of Pulmonary and Critical Care Medicine, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410005, Hunan, China

    Huan Yang, Jun Cao, Jian-Min Li & Cheng Li

  2. Department of Cardiovascular Surgery, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410005, Hunan, China

    Wen-Wu Zhou

  3. Department of Cardio-Thoracic Surgery, Hunan Children’s Hospital, Changsha, 410007, Hunan, China

    Jin-Wen Luo

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  1. Huan Yang
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Contributions

HY and JWL conceived and designed the experiments. HY and JWL wrote the main manuscript text and prepared Figs. 1–8. JC, JML, CL, and WWZ prepared Figs. 1–8 and analyzed the data. All authors reviewed the manuscript.

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Correspondence to Jin-Wen Luo.

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Yang, H., Cao, J., Li, JM. et al. Exploration of the molecular mechanism of tea polyphenols against pulmonary hypertension by integrative approach of network pharmacology, molecular docking, and experimental verification. Mol Divers (2023). https://doi.org/10.1007/s11030-023-10700-z

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