Objective:

2

To explore the effect and mechanism of schisandrin B (Sch B) in the treatment of cerebral ischemia in rats.

Methods:

2

The cerebral ischemia models were induced by middle cerebral artery occlusion (MCAO) and reperfusion. Sprague-Dawley rats were divided into 6 groups using a random number table

including sham

MCAO

MCAO+Sch B (50 mg/kg)

MCAO+Sch B (100 mg/kg)

MCAO+Sch B (100 mg/kg)+LY294002

and MCAO+Sch B (100 mg/kg)+wortmannin groups. The effects of Sch B on pathological indicators

including neurological deficit scores

cerebral infarct volume

and brain edema

were subsequently studied. Tissue apoptosis was identified by terminal transferase-mediated dUTP nick end-labeling (TUNEL) staining. The protein expressions involved in apoptosis

inflammation response and oxidative stress were examined by immunofluorescent staining

biochemical analysis and Western blot analysis

respectively. The effect of Sch B on phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling was also explored.

Results:

2

Sch B treatment decreased neurological deficit scores

cerebral water content

and infarct volume in MCAO rats (

P

<

0.05 or

P

<

0.01). Neuronal nuclei and TUNEL staining indicated that Sch B also reduced apoptosis in brain tissues

as well as the Bax/Bcl-2 ratio and caspase-3 expression (

P

<

0.01). Sch B regulated the production of myeloperoxidase

malondialdehyde

nitric oxide and superoxide dismutase

as well as the release of cytokine interleukin (IL)-1β and IL-18

in MCAO rats (

P

<

0.05 or

P

<

0.01). Sch B promoted the phosphorylation of PI3K and AKT. Blocking the PI3K/AKT signaling pathway with LY294002 or wortmannin reduced the protective effect of Sch B against cerebral ischemia (

P

<

0.05 or

P

<

0.01).

Conclusions:

2

Sch B reduced apoptosis

inflammatory response

and oxidative stress of MCAO rats by modulating the PI3K/AKT pathway. Sch B had a potential for treating cerebral ischemia.