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Salvia Miltiorrhiza Nanovesicles: A Strategy to Reprogram Myeloid Cells for Atherosclerosis Therapy via Immune
Hongjun Xu1, Rui Zhang1,2, Ruoyu Wu1
1Hebei Provincial Engineering Laboratory of Plant Bioreactor Preparation Technology, Hebei University of Chinese Medicine, No. 326 Xinshi South Road, Qiaoxi District, Shijiazhuang 050090 Hebei, China.
Introduction:
Research has shown that herbal medicine-derived vesicles act as biological agents and drug carriers. This study explores how Salvia miltiorrhiza nanovesicles alleviate atherosclerosis by regulating myeloid cells and inflammation.
Methods:
We prepared SDNVs using high-speed centrifugation and analyzed them with nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and live imaging. Atherosclerosis was studied in ApoE-/- mice using models with bone marrow-derived macrophages (BMDM) and monocyte-derived macrophages (MDM). Macrophages were classified with immunofluorescence staining, and cytokines and inflammatory factors were measured using qRT-PCR and ELISA. Flow cytometry identified bone marrow stem cells, progenitor cells, and blood cell types.
Results:
SDNVs exhibited characteristics of plant extracellular vesicles and significantly lowered total cholesterol, triglycerides, and LDL levels in atherosclerotic mice. Immunofluorescence staining showed fewer pro-inflammatory (M1) macrophages and more anti-inflammatory (M2) macrophages in arterial plaques. qRT-PCR and ELISA revealed reduced levels of inflammatory markers in the aorta and serum. Flow cytometry showed decreased bone marrow hematopoietic stem cells (Lin- Sca-1+ cKit+), progenitor cells (MPP4), and monocytes and neutrophils in peripheral blood. SDNVs also inhibited M1 polarization and promoted M2 polarization in BMDMs.
Discussion:
SDNVs exert potent anti-atherosclerotic effects through lipid regulation and immune modulation, thus advancing PDEV-based therapeutic strategies for atherosclerosis. Limitations involve the use of a single ApoE-/- mouse model and unclear underlying mechanisms of cellular SDNV uptake.
Conclusion:
SDNVs demonstrate immune-regulating and anti-inflammatory effects. They effectively enter the body and modulate bone marrow cell, blood cell production, macrophage behavior, and inflammation, thereby slowing the progression of atherosclerosis.
