Formononetin recovered injured nerve functions by enhancing synaptic plasticity in ischemic stroke rats

Biochem Biophys Res Commun. 2020 Feb 17:S0006-291X(20)30281-3. doi: 10.1016/j.bbrc.2020.02.015. Online ahead of print.

Abstract

Background and objectives: Formononetin has protective effect against ischemic stroke. It's unclear whether it can restore the nerve functions after stroke.

Methods: SD rats were subjected with middle cerebral artery occlusion (MCAO), and divided into sham, model and formononetin (30 mg/kg) groups. Neurobehavioral tests (modified Neurological Severity Score [mNSS] and rotarod) were performed before and at 1, 3, 7 and 14 days after MCAO. Then, the rats were sacrificed and the brain sections were processed for neuronal differentiation and synaptic plasticity.

Results: Compared with the sham group, the scores of mNSS were significantly increased, and the residence time on the rotating drum was significantly decreased in the MCAO rats. Compared with the model group, the scores of mNSS were significantly decreased, and the residence time on the rotating drum was increased in the formononetin (30 mg/kg) group. Formononetin significantly increased the number of neuronal dendritic spines and the expression of β III-tubulin, GAP-43, NGF, BDNF, p-Trk A, p-Trk B, p-AKT and p-ERK 1/2.

Conclusions: Formononetin recovered injured nerve functions after ischemic stroke. PI3K/AKT/ERK pathway might involve in the beneficial effect of formononetin on the neuronal differentiation and synaptic plasticity.

Keywords: Brain derived neurotrophic factor; Formononetin; Nerve growth factor; Neuronal differentiation; PI3K/AKT/ERK; Synaptic plasticity.