Gastroenterology and Hepatology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran.
Department of Biology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran.
Neurochem Res. 2024 Jul;49(7):1863-1878. doi: 10.1007/s11064-024-04143-7. Epub 2024 May 16.
The study aimed to assess 𝛾-Terpinene's (𝛾-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. 𝛾-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. 𝛾-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. 𝛾-TER show cased neuroprotective effects by suppressing inflammation, apoptosis, and oxidation. In conclusion, 𝛾-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 𝛾-TER as a potential therapeutic agent for ischemic stroke.
本研究旨在评估γ-松油烯（γ-TER）在急性脑缺血中的神经保护潜力，急性脑缺血的特征是大鼠脑血流减少。采用大脑中动脉闭塞（MCAO）作为诱导脑缺血的标准方法，对雄性 Wistar 大鼠进行干预。在再灌注开始时，腹腔内给予不同剂量（5、10 和 15mg/kg）的γ-TER。采用不同技术评估神经功能结局、脑梗死面积、脑水肿和脑内酶活性（SOD、GPx 和过氧化氢酶）。该研究使用 Cytoscape 软件评估与神经炎症和细胞凋亡相关的基因表达和途径，确定了涉及的前 10 个基因。通过实时 PCR 和 ELISA 评估促炎和促凋亡因子，通过 TUNEL 和流式细胞术检测细胞凋亡率。免疫组织化学评估缺血区凋亡相关蛋白如 Bax 和 bcl-2。γ-TER，特别是在 10 和 15mg/kg 剂量下，显著降低了神经功能缺损和脑梗死面积。与对照组相比，15mg/kg 剂量可减轻皮质、海马和纹状体中 TNF-α、IL-1β、Bax 和 caspase-3 基因和蛋白水平。此外，这些区域的 Bcl-2 水平增加。γ-TER 通过抑制炎症、细胞凋亡和氧化发挥神经保护作用。总之，γ-TER 具有天然的抗炎和抗凋亡特性，通过减少梗死、水肿、氧化应激和炎症来保护大脑免受缺血损伤。它调节与不同脑区细胞凋亡相关的关键基因和蛋白的表达。这些发现使 γ-TER 成为治疗缺血性中风的潜在治疗剂。
