Data from: Diosmin and its glycocalyx restorative and anti-inflammatory effects on injured blood vessels

Endothelium, a crucial homeostatic organ, regulates vascular permeability
and tone. Under physiological conditions, endothelial stimulation induces
vasodilator endothelial nitric oxide (eNO) release and prevents adhesion
molecule accessibility and leukocyte adhesion and migration into vessel
walls. Endothelium dysfunction is a principal event in cardiovascular
disorders, including atherosclerosis. Hence, current therapies focus on
endothelium repair to prevent downstream cardiovascular events. However,
minimal attention is given to the restoration of mechanotransducer
endothelial glycocalyx (GCX), a negatively charged heterogeneous
polysaccharide, which covers and protects endothelial cells. Endothelial
GCX shedding plays a role in endothelial dysfunction, increasing vascular
permeability and decreasing vessel tone. Diosmin, a flavone glycoside of
diosmetin, downregulates adhesive molecule expression, decreases
inflammation and capillary permeability, and upregulates eNO expression.
Due to these pleiotropic effects of diosmin on the vasculature, a possible
unidentified mechanism of action is through GCX restoration. Diosmin
effect on GCX and endothelial function were assessed in a partial ligation
left carotid artery (LCA) mouse model where the right carotid artery was
the control for each mouse. Diosmin (50 mg/kg) was administered daily for
7 days, 48 hours after ligation. Within the ligated mice LCAs, diosmin
treatment elevated the activated eNO synthase level, inhibited
inflammatory cell uptake, decreased vessel wall thickness, increased
vessel diameter, and increased GCX coverage of the vessel wall. ELISA
showed a decrease in hyaluronan concentration in plasma samples of
diosmin-treated mice, signifying reduced GCX shedding. In summary, diosmin
supported endothelial GCX integrity, which preserved endothelial function
by attenuating expression of inflammatory factors and restoring vascular
tone.