Abstract
Background
Microglia-mediated inflammation is one of the key aggravating factors in the development of ischemic stroke. Therefore, ameliorating microglial over-activation is a potential therapeutic target for ischemic injury. Thymol is a monophenol isolated from plant essential oil, which has various beneficial biological activities including anti-inflammatory and antioxidant, and protective effects in many disease models. However, its effects on ischemic stroke or microglial inflammation have not been reported.
Methods
Rodent transient middle cerebral artery occlusion (tMCAO) model was established to simulate ischemic stroke. TTC, modified neurological function score (mNSS) and behavioral tests were used to assess the severity of neurological damage. Then immunofluorescence staining and cytoskeleton analysis were used to determine activation of microglia. Lipopolysaccharide (LPS) was utilized to induce the inflammatory response of primary microglia in vitro. Quantitative real-time polymerase chain reaction (qRT-PCR), western blot and enzyme-linked immunosorbent assay (ELISA) were performed to exam the expression of inflammatory cytokines. And western blot was used to investigate the mechanism of the anti-inflammatory effect of thymol.
Results
In this study, we found that thymol treatment could ameliorate post-stroke neurological impairment and reduce infarct volume by reducing microglial activation and pro-inflammatory response (IL-1β, IL-6 and TNF-α). Mechanically, thymol could inhibit the phosphorylation of phosphatidylinositol-3-kinase (PI3K), sink serine/threonine kinase (Akt) and mammalian target of rapamycin (mTOR), and suppress the activation of nuclear factor-κB (NF-κB).
Conclusions
Our study demonstrated that thymol could reduce the microglial inflammation by targeting PI3K/Akt/mTOR/NF-κB signaling pathway, and further alleviate ischemic brain injury, suggesting that thymol is a promising candidate as a neuroprotective agent against ischemic stroke.