Berberine alleviates acute embolism-induced lung inflammation and injury by suppressing miR-22-5p expression and modulating the TLR4/NF-κB signaling pathway

Abstract

Context

Acute pulmonary embolism (APE) caused by blood clotting in pulmonary arteries triggers lung microvascular leakage and inflammation. While APE significantly affects right ventricular function, the associated lung injury and inflammation mechanisms remain understudied. Berberine has been established as an effective anti-inflammatory compound in traditional medicine.

Objective

To investigate whether berberine can prevent APE-associated inflammation and pulmonary hypertension, potentially facilitating thrombus resolution in pulmonary arteries.

Materials & methods

We employed pulmonary artery smooth muscle cells (PASMCs) treated with platelet-derived growth factor (PDGF) as an in vitro pulmonary embolism model and Sprague-Dawley rats treated with blood clot suspension as an in vivo model. Berberine treatment, miR-22-5p modulation and toll-like receptor (TLR4) overexpression were performed to elucidate the underlying mechanisms.

Results

Berberine treatment attenuated PDGF-induced proliferation of PASMCs in a dose-dependent manner. In the APE model, berberine administration significantly reduced elevated right ventricular systolic pressure (RVSP) and mean pulmonary arterial pressure (mPAP) while alleviating lung inflammation. Berberine treatment downregulated miR-22-5p expression in lung tissue, whereas miR-22-5p overexpression in lungs exacerbated lung inflammation responses. Conversely, miR-22-5p inhibition attenuated lung inflammation and hypertension status. Moreover, miR-22-5p overexpression increased the protein levels of TLR4 and nuclear factor kappa B (NF-κB), whereas miR-22-5p inhibition reduced them. Berberine treatment decreased the levels of miR-22-5p, TLR4, and NF-κB, while TLR4 overexpression reversed the beneficial effects of berberine treatment.

Discussion and conclusion

Our findings suggest that berberine treatment prevents pulmonary hypertension and lung inflammation associated with APE through inhibition of the miR-22-5p/TLR4/NF-κB signaling pathway.