Clematichinenoside Serves as a Neuroprotective Agent Against Ischemic Stroke: The Synergistic Action of ERK1/2 and cPKC Pathways
Authors: Zhichao Tang
Xu Zhang
Qianming Du
Chao Liu
Yunman Li
Hui Ji
Journal: Frontiers in Cellular Neuroscience (2016)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: ERK1/2; apoptosis; cPKC; clematichinenoside; stroke.
Affiliations: State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University Nanjing, China., State Key Laboratory of Natural Medicines, Department of Pharmacology, China Pharmaceutical University Nanjing, China., Department of Combine Traditional Chinese and Western Medicine, College of Clinical Medicine, Chengdu University of TCM Chengdu, China., State Key Laboratory of Natural Medicines, Department of Pharmacochemistry, China Pharmaceutical University Nanjing, China.

Abstract:  There are numerous evidences suggesting that inhibition of apoptosis of neurons play a critical role in preventing the damage and even death of neurons after brain ischemia/reperfusion, which shows therapeutic potential for clinical treatment of brain injury induced by stroke. In this study, we aimed to investigate the neuroprotective effect of Clematichinenoside (AR) and its underlying mechanisms. MCAO mode was performed in rats and OGD/R model in primary cortical neurons to investigate the neuroprotective effect of AR. The rate of apoptotic cells was measured using TUNEL assay in cerebral cortex and flow cytometric assay in cortical neurons. Apoptosis-related proteins such as bcl-2, bcl-xl, and bax and the phosphorylation of ERK1/2, cPKC, p90RSK, and CREB in ischemic penumbra were assayed by western blot. Furthermore, we made a thorough inquiry about how these proteins play roles in the anti-apoptotic mechanism using targets-associated inhibitors step by step. The results revealed that AR could activate both ERK1/2 and cPKC which resulted in p90RSK phosphorylation and translocation into the nucleus. Moreover, CREB, a downstream target of p90RSK, was phosphorylated and then bound to cAMP-regulated enhancer (CRE) to activate apoptosis-related genes, and finally ameliorate ischemic stroke through preventing neuron death. In conclusion, these data strongly suggest that AR could be used as an effective neuroprotective agent to protect against ischemic stroke after cerebral I/R injury through regulating both ERK1/2 and cPKC mediated p90RSK/CREB apoptotic pathways. 

Retracted: Yes

PubPeer comments:
 This publications contains figure items that were also published in https: doi.org 10.1016 j.neuropharm.2015.02.022 ![file] ![file] ![file] , 
 The journal retracts the 12 January 2016 article cited above. Following publication, it has been brought to our attention that several figures included in the article above appear identical to figures published by the authors in a separate article, u201cThe neuroprotective effect of a novel agent N2 on rat cerebral ischemia associated with the activation of PI3K Akt signaling pathwayu201d (doi: 10.1016 j.neuropharm.2015.02.022), published in Neuropharmacology, February 2015. Specifically, the Bax-sham and Bax-AR(32 mg kg) panels in Figure 2A of the Frontiers in Cellular Neuroscience publication appear identical to the D and F panels in Figure 5C of the Neuropharmacology publication, respectively. The TUNEL-AR(16 mg kg) panel in Figure 2A of the Frontiers in Cellular Neuroscience publication also appears identical to panel C in Figure 4A of the Neuropharmacology publication. The authors concur with the retraction and sincerely regret any inconvenience this may have caused to the reviewers, editors, and readers of Frontiers in Cellular Neuroscience. ,