Effects of leonurine on intracerebral haemorrhage by attenuation of perihematomal edema and neuroinflammation via the JNK pathway.

Abstract

Perihematomal edema plays a critical role in secondary brain injury in intracerebral hemorrhage (ICH), which is associated with inflammation, hematoma toxicity and oxidative stress. In this work, we investigated the protective effects of leonurine, an alkaloid of Herbal Leonuri, and possible mechanisms to provide a basis for a new therapeutic approach for ICH treatment. In in vivo studies, we demonstrated for the first time that leonurine treatment substantially decreased perihematomal edema, ameliorated neurobehavioral function deficits, reduced apoptosis and protected injured cerebral tissue after ICH. These benefits appear to be ascribed to leonurine effectively attenuating bloodbrain barrier (BBB) breakdown in vivo, by inhibiting degradation of hemoglobin and alleviating inflammatory mediator release. In this study, BV-2 cells were exposed in vitro to oxyhemoglobin (OxyHb) at a concentration of 10 μM to mimic neuroinflammation after ICH. Consistent with the results of the in vivo study, leonurine significantly inhibited OxyHbinduced inflammatory proteins expression in BV-2 cells, mainly through inhibiting the c-Jun N-terminal kinase (JNK) signaling pathway. This is the first time that leonurine is proved to be capable to protect the injured cerebral tissue after ICH, based on alleviating neuroinflammation and attenuating BBB breakdown to ameliorate perihematomal edema.