Biochanin A inhibits endothelial dysfunction induced by IL‑6‑stimulated endothelial microparticles in Perthes disease
Jianhong Liu1, Chengsen Lin1, Boxiang Li2
1Department of Orthopedic Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China.
Abstract:
Endothelial dysfunction caused by the stimulation of endothelial microparticles (EMPs) by the inflammatory factor IL-6 is one of the pathogenic pathways associated with Perthes disease. The natural active product biochanin A (BCA) has an anti-inflammatory effect; however, whether it can alleviate endothelial dysfunction in Perthes disease is not known. The present in vitro experiments on human umbilical vein endothelial cells showed that 0-100 pg/ml IL-6-EMPs could induce endothelial dysfunction in a concentration-dependent manner, and the results of the Cell Counting Kit 8 assay revealed that, at concentrations of <20 µM, BCA had no cytotoxic effect. Reverse transcription-quantitative PCR demonstrated that BCA reduced the expression levels of the endothelial dysfunction indexes E-selectin and intercellular cell adhesion molecule-1 (ICAM-1) in a concentration-dependent manner. Immunofluorescence and western blotting illustrated that BCA increased the expression levels of zonula occludens-1 and decreased those of ICAM-1. Mechanistic studies showed that BCA inhibited activation of the NFκB pathway. In vivo experiments demonstrated that IL-6 was significantly increased in the rat model of ischemic necrosis of the femoral head, whereas BCA inhibited IL-6 production. Therefore, in Perthes disease, BCA may inhibit the NFκB pathway to suppress IL-6-EMP-induced endothelial dysfunction, and could thus be regarded as a potential treatment for Perthes disease.
Insights
Biochanin A (BCA) may treat Perthes disease by reducing IL-6-induced endothelial dysfunction. BCA inhibits the NFκB pathway, decreasing inflammatory markers and improving cell integrity.
Area of Science:
- Biochemistry
- Cell Biology
- Pathology
Background:
- Endothelial dysfunction, driven by IL-6 stimulated endothelial microparticles (EMPs), is implicated in Perthes disease pathogenesis.
- Biochanin A (BCA), a natural compound, exhibits anti-inflammatory properties, but its role in Perthes disease-related endothelial dysfunction is unexplored.
Purpose of the Study:
- To investigate the potential of biochanin A (BCA) in alleviating endothelial dysfunction associated with Perthes disease.
- To elucidate the underlying mechanisms of BCA's action on endothelial cells and inflammatory pathways.
Main Methods:
- In vitro studies using human umbilical vein endothelial cells exposed to IL-6-EMPs.
- Cell Counting Kit 8 assay for cytotoxicity, RT-qPCR for gene expression (E-selectin, ICAM-1), immunofluorescence, and Western blotting for protein expression (ZO-1, ICAM-1).
- In vivo validation in a rat model of femoral head ischemic necrosis.
Main Results:
- IL-6-EMPs induced endothelial dysfunction in a dose-dependent manner.
- BCA (<20 µM) showed no cytotoxicity and reduced E-selectin and ICAM-1 expression.
- BCA increased zonula occludens-1 (ZO-1) expression and inhibited NFκB pathway activation.
- BCA suppressed IL-6 production in vivo.
Conclusions:
- BCA may mitigate IL-6-EMP-induced endothelial dysfunction in Perthes disease by inhibiting the NFκB pathway.
- BCA demonstrates potential as a therapeutic agent for Perthes disease.
