Effect of ß-patchoulene on cerebral ischemia-reperfusion injury and the TLR4/NF-κB signaling pathway.

ABSTRACT

ß-patchoulene (ß-PAE), an active constituent of the Pogostemon cablin, is well known for its anti-inflammatory and antioxidative functions in various diseases. However, little is known about the impact of ß-PAE on the cerebral ischemia-reperfusion (I/R) injury. The current study aimed to determine the neuroprotective effect of ß-PAE and the underlying mechanisms on cerebral I/R injury. Following pretreatment with ß-PAE (10 mg/kg body weight) by tail intravenous injection for 1 h, Sprague-Dawley rats were subjected to middle cerebral artery occlusion for 2 h and reperfusion for 24 h. The results indicated that pretreatment with ß-PAE could diminish the infarct volume, decrease the brain water content, reduce the neurological deficit score and restore the mitochondrial membrane potential, compared with the untreated I/R injury group. Furthermore, cell apoptosis was markedly suppressed by ß-PAE, and this effect was associated with the decreased apoptosis regulator BAX/apoptosis regulator Bcl-2 expression ratio and caspase-3 activity. In addition, ß-PAE significantly inhibited the release of proinflammatory factors, including tumor necrosis factor-α, interleukin (IL)-1ß and IL-6. Superoxide generation and malondialdehyde levels were reduced while the levels of glutathione peroxidase and superoxide dismutase were elevated following treatment with ß-PAE, indicating the antioxidative role of ß-PAE in cerebral I/R injury. Furthermore, the Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway was inhibited by ß-PAE, as demonstrated by the decreased TLR4 expression and nuclear translocation of p65, and increased IκBα level. Taken together, the results suggested that ß-PAE may exhibit a neuroprotective effect on cerebral I/R injury in rats through inactivating the TLR4/NF-κB signaling pathway.