Geniposide protects against hypoxia/reperfusion-induced blood-brain barrier impairment by increasing tight junction protein expression and decreasing inflammation, oxidative stress, and apoptosis in an in vitro system.
The blood-brain barrier (BBB) is involved in the pathogeneses of ischemic stroke (IS). Geniposide (GEN), an iridoid glycoside isolated from Gardenia jasminoides Ellis, has been used for the treatment of IS. However, the effects of GEN on the BBB are poorly understood. In vitro disease models of the BBB could be very helpful for the elucidation of underlying mechanisms and the development of novel therapeutic strategies. Therefore, we established an in vitro BBB model composed of primary cultures of brain microvascular endothelial cells and astrocytes. We then used this in vitro model to investigate the effect of GEN on the function of the BBB. Oxygen glucose deprivation and reoxygenation (OGD/R) significantly increased permeability and cell apoptosis in this in vitro BBB model. Notably, GEN pretreatment effectively improved the BBB function by decreasing the permeability of the BBB, promoting expression of tight junction proteins (zonula occludens-1, claudin-5, and occludin) and gamma-glutamyl transpeptidase, increasing transendothelial electrical resistance, mitigating oxidative stress damage and the release of inflammatory cytokines, downregulating the expression levels of matrix metallopeptidases-9 (MMP-9) and MMP-2, and increasing the release of brain derived neurotrophic factor and glial cell derived neurotrophic factor. Therefore, GEN can ameliorate the BBB dysfunction induced by OGD/R conditions through multiple protective mechanisms. The findings suggest that GEN may be an appropriate drug for restoring the barrier function of the BBB.
['Li|Changxiang|C|', 'Wang|Xueqian|X|', 'Cheng|Fafeng|F|', 'Du|Xin|X|', 'Yan|Juntang|J|', 'Zhai|Changming|C|', 'Mu|Jie|J|', 'Wang|Qingguo|Q|']
D000818:Animals D017209:Apoptosis D001812:Blood-Brain Barrier D015687:Cell Hypoxia D019610:Cytoprotection D039823:Iridoids D009414:Nerve Growth Factors D018384:Oxidative Stress D010100:Oxygen D051381:Rats D017207:Rats, Sprague-Dawley D015427:Reperfusion Injury D062725:Tight Junction Proteins
Geniposide Tight junction Oxygen glucose deprivation and reoxygenation Anti-apoptotic Anti-inflammatory In vitro blood-brain barrier