Phytochemicals as potential inhibitors of NETosis: implications for immunothrombosis and chronic disease management
Journal
BMC Complementary Medicine and Therapies
Journal Volume
26
Journal Issue
1
Start Page
Article number: 43
ISSN
2662-7671
Date Issued
2026-01-07
Author(s)
Abstract
Background
NETosis, a specialized form of neutrophil cell death, plays a dual role in immune regulation. While NET formation is essential for capturing pathogens, excessive NETosis contributes to immunothrombosis, oxidative stress, and tissue damage, affecting both acute and chronic diseases such as COVID-19, cardiovascular diseases, diabetes, cancer, and autoimmune conditions. Given the limitations of current treatments, including toxicity, high costs, and bleeding risks, phytochemicals are being explored for their therapeutic potential.
Methods
NETosis gene sets were collected through published data, and followed by Gene set enrichment analysis (GSEA) to identify potential NETosis-inhibiting natural compounds from a library of 103 phytochemicals candidates. NETosis phenotype was confirmed by assessing NET formation through immunofluorescence staining and quantification. Candidate compounds were further validated in vitro using RT-qPCR to assess the expression of NETosis-related genes, including PADI4, TREM1, S100A8/A9, and CCL7. To evaluate the procoagulant consequences of NETosis, we performed a thrombin activity assay by incubating plasma with conditioned media from treated neutrophil-like cells.
Results
Three phytochemicals—hesperidin, baicalin, and imperatorin—were identified as effective inhibitors of NETosis. Immunofluorescence staining confirmed NET inhibition, and RT-qPCR analysis showed significant downregulation of key genes involved in NET formation. In addition, thrombin activity was significantly reduced in plasma exposed to conditioned media from phytochemical-treated cells, indicating attenuation of NETosis-associated procoagulant activity.
Conclusions
Hesperidin, baicalin, and imperatorin show promise as candidates for modulating NETosis, with implications for managing immunothrombosis and chronic diseases.
Subjects
Immunothrombosis
Inflammation
NETosis
Neutrophils
Phytochemicals
Thrombosis
Publisher
BioMed Central Ltd
Type
journal article