Effects of Citrus Flavonoids Against Microvascular Damage Induced by Hypoperfusion and Reperfusion in Rat Pial Circulation

Microcirculation. 2015 Jul;22(5):378-90. doi: 10.1111/micc.12207.


Objective: The aim of the present study was to investigate the in vivo protective effects of hesperidin or diosmin or apigenin on damage induced by transient BCCAO and reperfusion.

Methods: Rat pial microcirculation was observed through a closed cranial window, using fluorescence microscopy. Pial arterioles were classified in five orders according to the Strahler's method.

Results: After 30 BCCAO and 60 minutes reperfusion, rats showed decreased arteriolar diameter, microvascular leakage, leukocyte adhesion, and reduction in capillary perfusion. Hesperidin and diosmin abolished the reduction in arteriolar diameter, while higher dose apigenin induced dilation by 21.7 ± 2.0% in order three arterioles RE. Nitric oxide synthase inhibition attenuated significantly hesperidin or diosmin or apigenin's effects on arteriolar diameter. Moreover, all these substances reduced microvascular leakage as well as leukocyte adhesion in dose-related manner, while capillary perfusion was protected. Furthermore, reduction in infarcted area and decrease in ROS production were observed.

Conclusions: Hesperidin, diosmin, and apigenin showed dose-related protective effects on hypoperfusion-reperfusion injury, causing nitric oxide release and attenuating tissue edema and leukocyte adhesion.

Keywords: bilateral common carotid artery occlusion; diosmin apigenin; hesperidin; nitric oxide release; pial microcirculation; reactive oxygen species; reperfusion.

MeSH terms

  • Animals
  • Apigenin / chemistry
  • Apigenin / pharmacology*
  • Arterioles / physiopathology
  • Citrus / chemistry
  • Diosmin / chemistry
  • Diosmin / pharmacology*
  • Hesperidin / chemistry
  • Hesperidin / pharmacology*
  • Male
  • Microcirculation / drug effects*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / metabolism
  • Rats
  • Rats, Wistar
  • Reperfusion
  • Vasodilation / drug effects*


  • Diosmin
  • Apigenin
  • Hesperidin
  • Nitric Oxide Synthase