Methylophiopogonanone A Protects against Cerebral Ischemia/Reperfusion Injury and Attenuates Blood-Brain Barrier Disruption In Vitro

Abstract

Methylophiopogonanone A (MO-A), an active homoisoflavonoid of the Chinese herb Ophiopogon japonicus which has been shown to have protective effects on cerebral ischemia/reperfusion (I/R) injury, has been demonstrated to have anti-inflammatory and anti-oxidative properties. However, little is known about its role in cerebral I/R injury. Therefore, in this study, by using a middle cerebral artery occlusion (MCAO) and reperfusion rat model, the effect of MO-A on cerebral I/R injury was examined. The results showed that MO-A treatment reduced infarct volume and brain edema, improved neurological deficit scores, reversed animal body weight decreases, and increased animal survival time in the stroke groups. Western blotting showed that MO-A suppressed MMP-9, but restored the expression of claudin-3 and claudin-5. Furthermore, transmission electron microscopy were monitored to determine the blood–brain barrier (BBB) alterations in vitro. The results showed that MO-A markedly attenuated BBB damage in vitro. Additionally, MO-A inhibited ROS production in ECs and MMP-9 release in differentiated THP-1 cells in vitro, and suppressed ICAM-1 and VCAM-1 expression in ECs and leukocyte/EC adhesion. In conclusion, our data indicate that MO-A has therapeutic potential against cerebral I/R injury through its ability to attenuate BBB disruption by regulating the expression of MMP-9 and tight junction proteins.

Synthesis and Biological Evaluation of Novel Homoisoflavonoids for Retinal Neovascularization

“…In addition, it was more potent and endothelial-cell specific than previously described antiangiogenic homoisoflavonoids. 5, 11-14 Given this, we tested it in a secondary cell proliferation assay, which monitors the incorporation of a thymidine analogue 5-ethynyl-2′-deoxyuridine into DNA of proliferating HRECs. Here, we confirmed the dose-dependent inhibition of HREC proliferation by 14a , without any signs of apoptotic nuclear morphology (Supplementary Figure 1).…”

“…12 Of natural-source homoisoflavanones, methylophiopogonanone B blocked HUVEC angiogenesis and the hypoxic response in vitro, 13 while very recently methylophiopogonanone A was shown to block brain endothelial cell activation. 14 In addition, considerable work has documented antiangiogenic effects of the related chalcones, flavones and flavanones. 8, 15 However, to our knowledge no systematic exploration of this class of compounds as antiangiogenic agents has been reported.…”

Naturally Occurring Homoisoflavonoids: Phytochemistry, Biological Activities, and Synthesis (Part II)

“…The former (9) has been shown to protect against cerebral ischemia/ reperfusion injury and attenuates blood-brain barrier disruption in vitro. 97…”

Cytotoxic Homoisoflavonoids from <i>Ophiopogon japonicus</i> Tubers

“…Homoisoflavonoids isolated from Ophigopogon have been shown to exert various biological activities including protective effects on cerebral ischemia/ reperfusion (I/R) injury, antioxidant, anti-inflammation and cytotoxic activities. [4][5][6][7][8] In the present study, a methanol extract of O. japonicus tubers showed strong cytotoxicity against human lung cancer cell lines. Phytochemical fractionation of the methanol extract of O. japonicus tubers led to the isolation of a homoisoflavanone (1), and three homoisoflavanes (2)(3)(4) (Fig.…”