Ginkgolide B reduces neuronal cell apoptosis in the traumatic rat brain: possible involvement of toll-like receptor 4 and nuclear factor kappa B pathway.

Ginkgolide B (GB) has been demonstrated to have a variety of pharmacological actions. Accumulating evidence indicates that GB may exert a protective effect on brain injury. The study was designed to investigate the influence of GB on toll-like receptor 4 (TLR-4) and nuclear factor κB (NF-κB)-dependent inflammatory responses and neuronal cell apoptosis after traumatic brain injury (TBI). Wistar rats were subjected to 5, 10 and 20 mg/kg GB daily for 5 days, intraperitoneally, following TBI. Rats were sacrificed at hour 2, 6 and 12, as well as day 1, 2, 3 and 5 after TBI. The administration of 10 and 20 mg/kg GB could significantly (least-significant difference test: p < 0.05) suppress gene expressions of TLR-4 and NF-κB, lessen concentrations of tumour necrosis factor α, interleukin-1β and interleukin-6, as well as reduce the number of apoptotic neuronal cells in traumatic rat brain tissues, but the administration of 5 mg/kg GB did not (p > 0.05). However, a clear concentration-response relationship was not found. Thus, GB may inhibit TLR-4 and NF-κB-dependent inflammatory responses, and furthermore lessen neuronal cell apoptosis after TBI, which may support the use of GB for the treatment of TBI.

Yu WH ，Dong XQ ，Hu YY ，Huang M ，Zhang ZY ... -  《-》

Ginkgolide B reduces neuronal cell apoptosis in the hemorrhagic rat brain: possible involvement of Toll-like receptor 4/nuclear factor-kappa B pathway.

Ginkgolide B (GB) is one of the ginkgolides that have been isolated from leaves and root bark of the Chinese tree Ginkgo biloba L. (Ginkgoaceae), and is a specific and potent antagonist of platelet activating factor. There is a large body of data showing that GB possesses a markedly neuroprotective property against ischemia-induced impairment in vivo and in vitro. Recently it has been found that GB can inhibit the inflammation in the rat brain tissues with ischemia/reperfusion injury and in the astrocytes treated with lipopolysaccharide, as well as protect neurons against beta-amyloid 25-35 and ischemia-induced apoptosis. However, there have been few reports on the influence of GB on intracerebral hemorrhage (ICH). This study was to investigate the effects of intraperitoneal GB on neuronal cell apoptosis, inflammatory cytokines and Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) pathway after ICH. Wistar rats obtained an intraperitoneal injection of 5, 10 and 20mg/kg GB after ICH once a day till day 5. Rats were sacrificed by decapitation at hour 2, 6 and 12, as well as day 1, 2, 3 and 5 after ICH. Gene expressions of TLR-4 and NF-κB, concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and interleukin-6 (IL-6) as well as number of apoptotic neuronal cells in hemorrhagic rat brain tissues were determined. The administration of 10 and 20mg/kg GB could significantly suppress gene expressions of TLR-4 and NF-κB, lessen concentrations of TNF-α, IL-1β and IL-6 as well as reduce number of apoptotic neuronal cells in hemorrhagic rat brain tissues by Least-significant Difference test (P<0.05), but the administration of 5mg/kg GB not (P>0.05). However, a clear concentration-response relationship was not found. GB may inhibit TLR4/NF-κB-dependent inflammatory responses, and furthermore lessen neuronal cell apoptosis after ICH, which may support the use of G. biloba extracts for the treatment of ICH.

Hu YY ，Huang M ，Dong XQ ，Xu QP ，Yu WH ，Zhang ZY ... -  《-》

Oxymatrine reduces neuronal cell apoptosis by inhibiting Toll-like receptor 4/nuclear factor kappa-B-dependent inflammatory responses in traumatic rat brain injury.

Dong XQ ，Yu WH ，Hu YY ，Zhang ZY ，Huang M ... -  《-》

Inhibition of NF-κB activation is associated with anti-inflammatory and anti-apoptotic effects of Ginkgolide B in a mouse model of cerebral ischemia/reperfusion injury.

Ginkgolide B (GB) has potent neuroprotective effects against ischemia-induced brain injury in vivo and in vitro. However, the underlying mechanisms of GB's neuroprotection remain poorly understood. Excessive inflammation and apoptosis contribute to the pathogenesis of ischemic brain damage, and NF-κB is considered to be a key player in these processes. In the present study, we examined the detailed mechanisms underlying the inhibitory effects of GB on inflammatory and apoptotic responses induced by focal cerebral ischemia/reperfusion (I/R). Transient middle cerebral artery occlusion (tMCAO) model was produced by using an intraluminal filament technique in mice. GB (10, 20 and 40 mg/kg) was administered intravenously (i.v.) 2h after MCAO. The results demonstrated that MCAO-induced cerebral injury was associated with an upregulation of p-IKK, p-IκB-α and degradation of IκB-α, indicating of NF-κB activation. Meanwhile activation of microglial and increases in levels of TNF-α, IL-1β and iNOS were observed. Furthermore upregulation of the expression of NF-κB target gene p53 and p53 downstream gene Bax, but downregulation of Bcl-2 and activation of caspase-3 were found. GB treatment showed marked reduction in infarction volume, brain edema and neurological deficits. GB also inhibited I/R induced NF-κB, microglia activation and production of pro-inflammatory cytokines. We also demonstrated that GB reduced Bax protein levels and increased Bcl-2 protein levels in the post-ischemic brains. These results suggest that GB's neuroprotection is attributable to its anti-inflammatory and anti-apoptotic effect through inhibition of NF-κB.

Gu JH ，Ge JB ，Li M ，Wu F ，Zhang W ，Qin ZH ... -  《-》

Progesterone administration modulates TLRs/NF-kappaB signaling pathway in rat brain after cortical contusion.

Chen G ，Shi J ，Jin W ，Wang L ，Xie W ，Sun J ，Hang C ... -  《ANNALS OF CLINICAL AND LABORATORY SCIENCE》