Schisandrin B Protects against Ischemic Brain Damage by Regulating PI3K/AKT Signaling in Rats

Objective To explore the effect and mechanism of schisandrin B(Sch B)in the treatment of cerebral ischemia in rats.Methods 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 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)-1βand 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 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.

Baicalin Reduces Early Brain Injury after Subarachnoid Hemorrhage in Rats

Objective: To evaluate the effect of baicalin on subarachnoid hemorrhage(SAH) in rats and explore the potential mechanisms. Methods: Sprague-Dawley rats underwent experimental SAH and received treatment with baicalin at 10 or 50 mg/kg after 2 and 12 h of SAH. Neurological scores, brain water content, Evans-blue extravasation, and levels of glutathione peroxidase(GSH-Px), superoxide dismutase(SOD), myeloperoxidase(MPO), and malondialdehyde(MDA) were measured 24 h after SAH. Expression of nuclear factor erythroid-related factor 2(Nrf2), NAD(P)H: quinone oxidoreductase 1(NQO1), matrix metalloproteinase-9(MMP-9), aquaporin 4(AQP4), occludin, and zonulaoccludens-1(ZO-1) were detected in the brain by Western blot. Heme oxygenase-1(HO-1) was detected by quantitative polymerase chain reaction, and tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) were assessed by enzyme-linked immunosorbent assay. Results: Baicalin attenuated EBI 24 h after SAH in rats(P<0.05). Baicalin elevated neurological scores, GSH-Px, SOD, and increased the expression of Nrf2, NQO1, HO-1, occludin, and ZO-1 in SAH rats(P<0.05 or P<0.01). Baicalin reduced MPO, MDA, and the expression of MMP-9, AQP4, TNF-α, and IL-1β(P<0.05 or P<0.01). Conclusion: Baicalin reduced SAH-induced EBI, partially via activation of the Nrf2/HO-1 pathway and inhibition of MMP-9 and AQP4.

Schisandrin B Inhibits NLRP3 Inflammasome Pathway and Attenuates Early Brain Injury in Rats of Subarachnoid Hemorrhage

Objective: To determine whether Schisandrin B(Sch B) attenuates early brain injury(EBI) in rats with subarachnoid hemorrhage(SAH). Methods: Sprague-Dawley rats were divided into sham(sham operation), SAH, SAH+vehicle, and SAH+Sch B groups using a random number table. Rats underwent SAH by endovascular perforation and received Sch B(100 mg/kg) or normal saline after 2 and 12 h of SAH. SAH grading, neurological scores, brain water content, Evan’s blue extravasation, and terminal transferase-mediated dUTP nick end-labeling(TUNEL) staining were carried out 24 h after SAH. Immunofluorescent staining was performed to detect the expressions of ionized calcium binding adapter molecule 1(Iba-1) and myeloperoxidase(MPO) in the rat brain, while the expressions of B-cell lymphoma 2(Bcl-2), Bax, Caspase-3, nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3(NLRP3), apoptosis-associated specklike protein containing the caspase-1 activator domain(ASC), Caspase-1, interleukin(IL)-1β, and IL-18 in the rat brains were detected by Western blot. Results: Compared with the SAH group, Sch B significantly improved the neurological function, reduced brain water content, Evan’s blue content, and apoptotic cells number in the brain of rats(P<0.05 or P<0.01). Moreover, Sch B decreased SAH-induced expressions of Iba-1 and MPO(P<0.01). SAH caused the elevated expressions of Bax, Caspase-3, NLRP3, ASC, Caspase-1, IL-1β, and IL-18 in the rat brain(P<0.01), all of which were inhibited by Sch B(P<0.01). In addition, Sch B increased the Bcl-2 expression(P<0.01). Conclusion: Sch B attenuated SAH-induced EBI, which might be associated with the inhibition of neuroinflammation, neuronal apoptosis, and the NLRP3 inflammatory signaling pathway.