Neuroprotective Effects of [Formula: See Text]-Terpinene in Rats with Acute Cerebral Ischemia: Modulation of Inflammation, Apoptosis, and Oxidation

The study aimed to assess ????-Terpinene's (????-TER) neuroprotective potential in acute cerebral ischemia, characterized by reduced cerebral blood flow in rats. Middle cerebral artery occlusion (MCAO), a standard method for inducing cerebral ischemia, was employed in male Wistar rats. ????-TER at varying doses (5, 10, and 15 mg/kg) were intraperitoneally administered during reperfusion onset. Neurological outcomes, cerebral infarct size, edema, and enzymatic activities (SOD, GPx, and catalase) in the brain were evaluated using diverse techniques. The study examined gene expression and pathways associated with neuroinflammation and apoptosis using Cytoscape software, identifying the top 10 genes involved. Pro-inflammatory and pro-apoptotic factors were assessed through real-time PCR and ELISA, while apoptotic cell rates were measured using the TUNEL and Flow cytometry assay. Immunohistochemistry assessed apoptosis-related proteins like Bax and bcl-2 in the ischemic area. ????-TER, particularly at doses of 10 and 15 mg/kg, significantly reduced neurological deficits and cerebral infarction size. The 15 mg/kg dose mitigated TNF-α, IL-1β, Bax, and caspase-3 gene and protein levels in the cortex, hippocampus, and striatum compared to controls. Furthermore, Bcl-2 levels increased in these regions. ????-TER show cased neuroprotective effects by suppressing inflammation, apoptosis, and oxidation. In conclusion, ????-TER, possessing natural anti-inflammatory and anti-apoptotic properties, shields the brain against ischemic damage by reducing infarction, edema, oxidative stress, and inflammation. It modulates the expression of crucial genes and proteins associated with apoptosis in diverse brain regions. These findings position ????-TER as a potential therapeutic agent for ischemic stroke.