TY  - EJOU
AU  - FU, LONGSHENG 
AU  - HU, JINFANG 
AU  - SHAO, FENG 
AU  - WU, YAOQI 
AU  - BAI, WEI 
AU  - JIANG, MINGJIN 
AU  - CHEN, HAO 
AU  - CHEN, LIHUA 
AU  - LV, YANNI 

TI  - Biochanin A, as the Lrg1/TGF-β/Smad2 pathway blockade, attenuates blood-brain barrier damage after cerebral ischemia-reperfusion by modulating leukocyte migration patterns
T2  - BIOCELL

PY  - 2023
VL  - 47
IS  - 8
SN  - 1667-5746

AB  -  <b>Background:</b> Biochanin A is an excellent dietary isoflavone that has the concomitant function of both medicine and foodstuff. The attenuation function of biochanin A on blood-brain barrier (BBB) damage induced by cerebral ischemia-reperfusion remains unclear. <b>Methods:</b> C57BL/6 mice were subjected to 1 h middle cerebral artery occlusion (MCAO) followed by 24 h reperfusion. The infarct volume of the brain was stained by TTC, while leakage of the brain was quantitatively stained by Evans blue, and the neurologic deficit score was measured. Microglial-induced morphologic changes were observed via immunofluorescence staining, and rolling and adhering leukocytes in venules were observed via two-photon imaging, while the inner fluorescein isothiocyanate-albumin of venules were compared with those of surrounding interstitial area through venular albumin leakage. <b>Results:</b> The attenuation effect of biochanin A on tight junction injury was compared in ischemia-reperfusion mice or conventional knockdown of leucine-rich α2-glycoprotein 1 (Lrg1) mice. Biochanin A could ameliorate BBB injury in mice with cerebral ischemia-reperfusion in a dose-dependent manner by strengthening the immunostaining volume of occludin, claudin-5, and zonula occludens-1. The amoeba morphologic changes of microglial combined with the elevated expression of Lrg1 could be relieved under the treatment of biochanin A. Biochanin A played a countervailing role on the rolling leukocytes in the vessel, while the leakage of blood vessels was reduced. Biochanin A diminished its functions to further improved attenuation for tight junction injury on conventional Lrg1-knockout mice, as well as the inhibition effects on TGF-β1, and the phosphorylation of suppressor of mothers against decapentaplegic 2 (Smad2)/Smad2 via western blot assay.  <b>Conclusion:</b> Biochanin A could alleviate tight junction injury induced by cerebral ischemia-reperfusion and blocked the Lrg1/TGF-β/Smad2 pathway to modulate leukocyte migration patterns.
KW  - Biochanin A; Blockade; Leukocyte migration; Blood-brain barrier damage; Ischemia-reperfusion; Lrg1

DO  - 10.32604/biocell.2023.028602