Icariside II, a phosphodiesterase 5 inhibitor, attenuates cerebral ischaemia/reperfusion injury by inhibiting glycogen synthase kinase‐3β‐mediated activation of autophagy

Abstract

Background and Purpose Cerebral ischaemia/reperfusion causes exacerbated neuronal damage involving excessive autophagy and neuronal loss. The present study was designed to investigate the effect of icariside II, one of main active ingredients of Herba Epimedii on this loss and whether this is related to its PDE 5 inhibitory action. Experimental Approach Focal cerebral ischaemia was induced in the rat by transient middle cerebral artery occlusion over 2 hr, followed by reperfusion with icariside II, 3‐methylamphetamine or rapamycin. The effect of icariside II was determined measuring behaviour changes and the size of the infarction. The expressions of PDE 5, autophagy‐related proteins and the level of phosphorylation of glycogen synthase kinase‐3β (GSK‐3β) were determined. Cultured primary cortical neurons were subjected to oxygen and glucose deprivation followed by reoxygenation in the presence and absence of icariside II. A surface plasmon resonance assay and molecular docking were used to explore the interactions of icariside II with PDE 5 or GSK‐3β. Key Results Icariside II not only protected against induced ischaemic reperfusion injury in rats but also attenuated such injury in primary cortical neurons. The neuroprotective effects of icariside II on such injury were attributed to interfering with the PKG/GSK‐3β/autophagy axis by directly bounding to PDE 5 and GSK‐3β. Conclusions and Implications These findings indicate that icariside II attenuates cerebral I/R‐induced injury via interfering with PKG/GSK‐3β/autophagy axis. This study raises the possibility that icariside II and other PDE 5 inhibitors maybe effective in the treatment ischaemia stroke.

WITHDRAWN: Combination of Paeoniflorin and Calycosin-7-glucoside Promotes Ischemic Stroke Recovery via the PI3K/AKT Signaling Pathway

“…Increasing Bcl-2 can inhibit apoptosis of nerve cells, while increasing BAX can promote apoptosis of nerve cells 35 . GSK-3β is mainly distributed in the nervous system and is a regulator of apoptosis 36 . It is involved in cell differentiation, proliferation and apoptosis.…”

Icariside II ameliorates myocardial ischemia and reperfusion injury by attenuating inflammation and apoptosis through the regulation of the PI3K/AKT signaling pathway

“…In conclusion, the findings of the present study suggested that the pretreatment with ICAII may alleviate MIRI by activating the PI3K/AKT signaling pathway, thereby attenuating inflammatory reactions and myocardial apoptosis. Nonetheless, the present study had several limitations; for example, in addition to anti-inflammatory and anti-apoptotic bioactivities, ICAII has been discovered to possesses antioxidant and autophagy regulatory properties (12,35). These pharmacological activities may be involved in the underlying protective mechanism of ICAII in MIRI; however, these cardioprotective effects of ICAII were not further investigated in vitro in the present study, thus further investigations are required to determine the involvement of these functions of ICAII in MIRI.…”

Synthesis of a New Phenyl Chlormethine-Quinazoline Derivative, a Potential Anti-Cancer Agent, Induced Apoptosis in Hepatocellular Carcinoma Through Mediating Sirt1/Caspase 3 Signaling Pathway

“…The X-ray crystal structure of human Sirt1 (PDB ID: 4ZZH) was obtained from the Protein Data Bank (PDB) archives and used as target for molecular docking. The docking results were written as a pose viewer file, and the protein-ligand complex interactions were evaluated by the PyMOL molecular graphics system as described in previous study ( Gao et al., 2020 ).…”

“…Western blot was performed as described previously (Gao et al, 2020). Briefly, the protein concentration was measured with BCA Protein Assay Kit.…”