8-Methoxypsoralen (8-MOP) has anti-inflammatory, antioxidant and tissue-repairing abilities. Here, we probed the function and mechanism of 8-MOP in traumatic brain injury (TBI). The in-vivo TBI model was constructed in Sprague-Dawley (SD) rats using controlled cortical impact (CCI) surgery. In parallel, BV2 microglia and HT22 neurons were activated by lipopolysaccharide (LPS) to establish an in-vitro model. The modified neurological score (mNSS) and the Morris water maze experiment were employed to evaluate the rats’ neurological functions. The rats’ brain edema was assessed by the dry and wet method, and neuronal apoptosis in damaged brain tissues was monitored by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) and Nissl’s staining. Immunohistochemistry (IHC) was applied to verify Iba1-microglial activation in brain lesions of rats. The expression of inflammatory cytokines in BV2 microglia and HT22 neurons in the injured lesion of TBI rats was examined by the enzyme-linked immunosorbent assay (ELISA). The levels of iNOS, COX2, TLR4, PPARγ, STAT3, and NF-κB in brain lesions, BV2 microglia and HT22 neurons were compared by Western blot. As a result, 8-MOP administration reduced inflammation and LPS-induced neuronal damage in BV2 microglia. In vivo, 8-MOP treatment relieved neurological deficits in TBI rats, improved cognitive, learning and motor functions and mitigated brain edema and neuroinflammation induced by TBI. Furthermore, LPS or TBI activated the NF-κB and STAT3 pathways and repressed the PPARγ expression. However, 8-MOP treatment attenuated NF-κB and STAT3 phosphorylation and elevated PPARγ levels. Hence, 8-MOP exerts neuroprotective and anti-inflammatory effects in TBI rats by modulating the PPARγ/NF-κB pathway.

8-甲氧基补骨脂素 (8-MOP) 具有抗炎、抗氧化和组织修复能力。在这里，我们探讨了 8-MOP 在创伤性脑损伤 (TBI) 中的作用和机制。使用受控皮质冲击 (CCI) 手术在 Sprague - Dawley (SD) 大鼠中构建体内 TBI模型。同时，BV2 小胶质细胞和 HT22 神经元被脂多糖 (LPS) 激活以建立体外模型。采用改良神经评分法(mNSS)和Morris水迷宫实验评价大鼠的神经功能。采用干法和湿法评估大鼠脑水肿情况，并通过末端脱氧核苷酸转移酶介导的dUTP-生物素缺口末端标记（TUNEL）和尼氏染色监测受损脑组织的神经元凋亡。应用免疫组织化学 (IHC) 来验证 Iba1-小胶质细胞在大鼠脑损伤中的激活。采用酶联免疫吸附试验（ELISA）检测TBI大鼠损伤病灶BV2小胶质细胞和HT22神经元炎症因子的表达。通过蛋白质印迹比较脑损伤、BV2小胶质细胞和HT22神经元中iNOS、COX2、TLR4、PPARγ、STAT3和NF-κB的水平。因此，8-MOP 给药减少了 BV2 小胶质细胞中的炎症和 LPS 诱导的神经元损伤。在体内，8-MOP 治疗减轻了 TBI 大鼠的神经功能缺损，改善了认知、学习和运动功能，并减轻了 TBI 引起的脑水肿和神经炎症。此外，LPS 或 TBI 激活 NF-κB 和 STAT3 通路并抑制 PPARγ 表达。然而，8-MOP 处理减弱了 NF-κB 和 STAT3 磷酸化并提高了 PPARγ 水平。因此，8-MOP 通过调节 PPARγ/NF-κB 通路对 TBI 大鼠发挥神经保护和抗炎作用。LPS 或 TBI 激活 NF-κB 和 STAT3 通路并抑制 PPARγ 表达。然而，8-MOP 处理减弱了 NF-κB 和 STAT3 磷酸化并提高了 PPARγ 水平。因此，8-MOP 通过调节 PPARγ/NF-κB 通路对 TBI 大鼠发挥神经保护和抗炎作用。LPS 或 TBI 激活 NF-κB 和 STAT3 通路并抑制 PPARγ 表达。然而，8-MOP 处理减弱了 NF-κB 和 STAT3 磷酸化并提高了 PPARγ 水平。因此，8-MOP 通过调节 PPARγ/NF-κB 通路对 TBI 大鼠发挥神经保护和抗炎作用。