Dalbergiae Odoriferae Lignum flavonoids (DOLF) improve microcirculatory disorders by suppressing neutrophil extracellular traps (NETs) in rats

Microcirculatory disorders, characterized by impaired blood flow in small vessels, are critical in conditions like ischemia-reperfusion injury, sepsis, and cardiovascular diseases, leading to organ damage. Current treatments often target vasodilation or anti-coagulation but may not fully address the underlying inflammatory and thrombotic components. Neutrophil extracellular traps (NETs), structures released by neutrophils, contribute significantly to microvascular occlusion and inflammation. Targeting NETs formation represents a novel therapeutic strategy to protect microcirculation and prevent organ dysfunction.

Sixty SPF-grade male Sprague-Dawley rats were divided into six groups: sham, model, nicorandil (1 mg·kg~(-1)), and low-, medium-, and high-dose DOLF (1, 2, and 4 g·kg~(-1)). Treatments were administered by gavage daily for 7 consecutive days. A model of microcirculatory disorders was induced by injecting polyethylene microspheres into the left ventricle. Researchers assessed blood flow, arterial/left ventricular pressure, plasma/whole blood viscosity, fibrinogen, and platelet function. Organ pathology was examined via HE staining. Serum biomarkers like CK, CK-MB, ALT, AST, GLU, and Crea were measured. NETs markers MPO and CitH3 were detected by tissue and cellular immunofluorescence, and inflammatory cytokines (TNF-α, ROS, IL-1β, IL-6) by ELISA and Western blot.

Compared to the model group, DOLF treatment significantly improved various parameters across all tested doses. It ameliorated hemodynamic abnormalities, including blood flow, arterial pressure, and left ventricular pressure. Microcirculatory dysfunction was reduced, as evidenced by improved microvascular morphological changes analyzed with AngioTool software. Hemorheological abnormalities, such as plasma viscosity, whole blood viscosity at low, medium, and high shear rates, fibrinogen levels, and platelet function parameters, were also improved. Crucially, DOLF reduced markers of neutrophil extracellular traps (NETs), including MPO and CitH3 in rat heart and brain tissues, and in isolated peripheral blood neutrophils. Inflammatory markers like serum TNF-α, ROS, and IL-1β were decreased, along with myocardial MPO, PAD4, TNF-α, and IL-6 protein expression determined by Western blot. Organ damage biomarkers (CK, CK-MB, ALT, AST, Crea) were also improved, suggesting broad protective effects across the heart, liver, lungs, kidneys, and brain. > While specific quantitative data (e.g., exact percentages or p-values) are not provided in the abstract, the findings consistently indicate a significant amelioration of disease pathology across multiple physiological and molecular endpoints.