Abstract：
Psychological stress induces neuroinflammatory responses, which are associated with the pathogenesis of various psychiatric disorders, such as posttraumatic stress disorder and anxiety. Osthole-a natural coumarin isolated from the seeds of the Chinese herb Cnidium monnieri-exerts anti-inflammatory and antioxidative effects on the central nervous system. However, the therapeutic benefits of osthole against psychiatric disorders remain largely unknown. We previously demonstrated that mice subjected to repeated social defeat stress (RSDS) in the presence of aggressor mice exhibited symptoms of posttraumatic stress disorder, such as social avoidance and anxiety-like behaviors. In this study, we investigated the therapeutic effects of osthole and the underlying molecular mechanisms. Osthole exerted therapeutic effects on cognitive behaviors, mitigating anxiety-like behaviors and social avoidance in a mouse model of RSDS. The anti-inflammatory response induced by the oral administration of osthole was strengthened through the upregulation of heme oxygenase-1 expression. The expression of PPARα was inhibited in mice subjected to RSDS. Nonetheless, osthole treatment reversed the inhibition of PPARα expression. We identified a positive correlation between heme oxygenase-1 expression and PPARα expression in osthole-treated mice. In conclusion, osthole has potential as a Chinese herbal medicine for anxiety disorders. When designing novel drugs for psychiatric disorders, researchers should consider targeting the activation of PPARα.
摘要：
心理压力诱导神经炎症反应，与各种精神疾病的发病机制有关，如创伤后应激障碍和焦虑。蛇床子素-一种从中草药Cnidiummonnieri种子中分离的天然香豆素-对中枢神经系统具有抗炎和抗氧化作用。然而,蛇床子素对精神疾病的治疗益处仍然未知。我们先前证明，在存在侵略者小鼠的情况下遭受反复的社交失败应激（RSDS）的小鼠表现出创伤后应激障碍的症状，比如社交回避和焦虑的行为。在这项研究中,我们研究了蛇床子素的治疗效果和潜在的分子机制。蛇床子素对认知行为有治疗作用，减轻RSDS小鼠模型中的焦虑样行为和社交回避。口服蛇床子素诱导的抗炎反应通过上调血红素加氧酶-1表达而增强。在接受RSDS的小鼠中，PPARα的表达受到抑制。尽管如此，蛇床子素治疗逆转了PPARα表达的抑制。我们发现，在蛇床子素处理的小鼠中，血红素加氧酶-1的表达与PPARα的表达呈正相关。总之,蛇床子素具有作为治疗焦虑症的中草药的潜力。在设计治疗精神疾病的新药时，研究人员应考虑靶向激活PPARα。
