Neuroprotective and Anti-Inflammatory Effects of Sonlicraomanol in Rat Cerebral Ischemia/Reperfusion Injury Is Achieved Through Improving Mitochondrial Function
Received Date: Dec 06, 2021 / Accepted Date: Jan 13, 2022 / Published Date: Jan 20, 2022
Abstract
Background: Mitochondrial improvement is the central player of neuroprotection following cerebral ischemia/ reperfusion injury (I/RI). The present study evaluated the neuroprotective and anti-inflammatory effects of a new mitochondrial-acting drug, sonlicraomanol (SONL), in rats with cerebral I/RI, by focusing on the role of mitochondrial ATP-sensitive potassium (mK-ATP) channels and mitochondrial biogenesis.
Methods: Cerebral I/RI was modeled in Sprague Dawley rats (n=36) through induction of two hours of local ischemia via middle cerebral artery occlusion, followed by 24 hours of reperfusion. SONL at the concentrations of 10 and 50μM was intraperitoneally administered to rats for one week before the onset of occlusion. Cerebral infarcted areas, brain activity, mitochondrial function and biogenesis, and the levels of pro-inflammatory cytokines were quantified by triphenyl-tetrazolium chloride, behavioral tests, fluorometry, immunoblotting, and ELISA, respectively.
Results: Administration of SONL significantly reduced cerebral infarct volume and neurological activity in a dosedependent manner, as compared with the untreated control group (p<0.01). SONL (50μM) significantly reversed the I/RI-induced changes in mitochondrial membrane depolarization, mitochondrial reactive oxygen species (mitoROS), superoxide dismutase (mnSOD), and pro-inflammatory cytokines TNF-α, IL-1β, IL-6 (p<0.01). As well, the expression of mitochondrial biogenesis proteins PGC-1α, NRF1, and TFAM was upregulated following SONL 50 μM treatment. Importantly, the inhibition of mK-ATP channels through 5-hydoxydecanoate significantly eliminated the neuroprotective, anti-inflammatory, and mitochondrial impacts of SONL.
Conclusion: SONL post-conditioning had a significant neuroprotective effect which was mediated through increasing mK-ATP channels activity and subsequent improvement of mitochondrial biogenesis and function, and reduction of inflammatory responses.
Citation: Wu W, Wang Y (2022) Neuroprotective and Anti-Inflammatory Effects of Sonlicraomanol in Rat Cerebral Ischemia/Reperfusion Injury Is Achieved Through Improving Mitochondrial Function. Cell Mol Biol, 68: 222. Doi: 10.4172/1165-158X.1000222
Copyright: © 2021 Wu W, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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