By Activating Akt/eNOS Bilobalide B Inhibits Autophagy and Promotes Angiogenesis Following Focal Cerebral Ischemia Reperfusion

Abstract

Background/Aims: Ischemic stroke is a leading cause of long-term disability. To date, there is no effective treatment for stroke. Previous studies have shown that Ginkgo biloba extract has protective effects against neurodegenerative disorders. In this present study, we sought to test the potential protective role of an active component of Ginkgo biloba extract, bilobalide, in a rat model of middle cerebral artery occlusion (MCAO). Methods: A rat model of MCAO was used to test the potential protective effects of Bilobalide B on stroke protection. TTC staining was performed to evaluate infarct size of the brains. Neurological deficit score was measured to reveal the effects of the treatments on animal behavior and cognition. Immunohistochemical staining and transmission electronic microscope analysis were performed to measure the cellular responses to drug treatment. Western blotting and ELISA were performed. The expression of Cleaved- Casepase 3, Beclin-1, p62 and LC3I/II were quantified, and the Phosphorylation of eNOS and Akt were evaluated. The ratio of Bcl-2/ Bax was determined to reveal the molecular pathways that are involved in the drug treatment. Results: We found that intraperitoneal delivery of various Bilobalide doses during ischemia can protect against brain injury, as evidenced by reduced infarct size and improved neurological scores after surgery. Histochemical analysis revealed that treatment with bilobalide can significantly reduce apoptosis, autophagy, and promote angiogeneis following ischemia/reperfusion injury to the brain. The performence of increased phosphorylation of eNOS and Akt suggested that bilobalide can activate Akt prosurvival and eNOS pathways to promote cell survival and angiogenesis, respectively. Conclusions: Our results suggested that bilobalide benefits stroke symptoms by reducing cell death pathways and promoting angiogenesis. As such, bilobalide may be a potential agent for improving self-repair after ischemic stroke.

Retracted: Bilobalide alleviates tumor necrosis factor‐alpha‐induced pancreatic beta‐cell MIN6 apoptosis and dysfunction through upregulation of miR‐153

“…In addition, BB was proved to function in declining inflammation, insulin resistance, and secretion of antigenic factors stimulated by hypoxia (Priyanka et al, ). Moreover, Zheng et al indicated that BB suppressed apoptosis, autophagy, and improved angiogenesis via AKT/endothelial nitric oxide synthase pathway (Zheng et al, ). BB was investigated to function in diverse cells and diseases, such as neural cell (Hua et al, ), SH‐SY5Y cells (Shi, Wu, Yew, Xu, & Zhu, ), gastric ulcer (Hui & Fangyu, ), and inflammatory pain (Goldie & Dolan, ).…”

RETRACTED ARTICLE: Bilobalide protects H9c2 cell from oxygen-glucose-deprivation-caused damage via upregulation of miR-27a

“…Bilobalide, a component extracted from Ginkgo biloba extract, possess various kinds of properties. For example, bilobalide revealed neuroprotective effects in brain ischemic injury [6]; Bilobalide showed antioxidant potential in alleviating hypoxia-induced injury in 3T3-L1 adipocytes [7]; Bilobalide inhibited autophagy and promoted angiogenesis in cerebral ischemia-reperfusion [8]. Importantly, bilobalide demonstrated functions in the protection of the mitochondrial respiratory activity [9,10].…”

<p>Nd₂O₃ Nanoparticles Induce Toxicity and Cardiac/Cerebrovascular Abnormality in Zebrafish Embryos via the Apoptosis Pathway</p>

“…We found that autophagy in cerebrovascular was downregulated in the 200 μg/mL group ( Figure 6K); however, in whole embryos, there was no change. Several studies have shown that decreased autophagy could inhibit pathways involved in angiogenesis 22 and autophagy triggered angiogenesis by activating VEGF and AKT. 23 Therefore, we hypothesised that the reduced autophagy level in cerebrovascular might contribute to cerebrovascular disappearance.…”