Astilbin protects against cerebral ischaemia/reperfusion injury by inhibiting cellular apoptosis and ROS-NLRP3 inflammasome axis activation
Authors: Yu Li
Feng Zhi
Rong Wang
Yilin Yang
Lian Xue
Journal: International Immunopharmacology (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Apoptosis; Astilbin; Ischaemic stroke; MAPK pathway; NLRP3 inflammasome
Affiliations: Department of Neurosurgery, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China., Department of Neurosurgery, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China; Modern Medical Research Center, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China., Modern Medical Research Center, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China., Department of Neurosurgery, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China. Electronic address: ., Department of Neurosurgery, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China; Modern Medical Research Center, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China. Electronic address: .

Abstract:  Background: Ischaemic stroke is a lethal cerebrovascular disease that occurs worldwide. Astilbin is a natural flavonoid compound with various physiological activities. The purpose of this study was to investigate the neuroprotective effects of Astilbin after cerebral ischaemia reperfusion (I/R) injury. Methods: The oxygen and glucose deprivation (OGD) model was used to simulate cerebral I/R injury in vitro. Cell viability was measured via CCK-8 and LDH release assays. Cell apoptosis was measured via Hoechst 33258 staining and flow cytometry assays. ROS was detected via flow cytometry assay. The protein expression levels were determined by western blotting. The middle cerebral artery occlusion (MCAO) model was used to simulate cerebral I/R injury in vivo. Cerebral ischaemic volume was measured by TTC staining. The Zea-Longa score, rota-rod test, and foot-fault test were used to evaluate behavioural changes and neurological deficits in rats. Results: Astilbin significantly enhanced cell viability and decreased LDH release after OGD treatment in vitro. Astilbin effectively curbed cell apoptosis induced by OGD via inhibiting the activation of caspase-3, decreasing the ratio of Bax/Bcl-2 and decreasing FADD. Astilbin also inhibited OGD-induced inflammation by suppressing ROS-NLRP3 inflammasome axis activation. Further results revealed that Astilbin could suppress the MAPK pathway and activate the PI3K/AKT pathway. Finally, Astilbin significantly reduced the cerebral infarction volume and relieved neurological deficits in rats in vivo. Conclusion: Astilbin could defend against cerebral I/R injury by inhibiting apoptosis and inflammation via suppressing the MAPK pathway and activating the AKT pathway. 

Retracted: No

PubPeer comments:
 Figure 3C and 4A: * Red boxes: The NLRP3 panel in Figure 3C looks remarkably similar to the p-P38 panel in Figure 4A, albeit stretched differently. ![file] , 
 #1 We highly appreciate your valuable comments! We have rechecked the original data. The first author, Yu Li, found that he made the low-level mistake as you indicated in Fig. 4A when he pasted WB images. For Figure 3C and Figure 4A, we will provide the uncropped original images to the editor to erratum. ,