Oral administration of osthole mitigates maladaptive behaviors through PPARα activation in mice subjected to repeated social defeat stress

IF 4.4 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Neurochemistry international Pub Date : 2024-07-23 DOI:10.1016/j.neuint.2024.105811
Chao-Wei Chen , Wei-Lan Yeh , Vichuda Charoensaensuk , Chingju Lin , Liang-Yo Yang , Mao-Kai Chen , Tong Yeh , Cheng-Fang Tsai , Dah-Yuu Lu
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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.

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通过激活PPARα,口服奥斯特孔能减轻反复遭受社交失败压力的小鼠的适应不良行为。
心理压力会诱发神经炎症反应,这与创伤后应激障碍和焦虑症等各种精神疾病的发病机制有关。从中草药蛇床子种子中分离出来的天然香豆素--蛇床子素对中枢神经系统具有抗炎和抗氧化作用。然而,osthole 对精神疾病的治疗效果在很大程度上仍不为人所知。我们曾证实,小鼠在攻击性小鼠在场的情况下受到重复社交失败应激(RSDS),会表现出创伤后应激障碍的症状,如社交回避和焦虑样行为。在这项研究中,我们探讨了蛇床子素的治疗作用及其分子机制。奥斯特孔对小鼠的认知行为有治疗作用,能减轻小鼠的焦虑样行为和社交回避。通过上调血红素加氧酶-1的表达,加强了口服奥斯特孔引起的抗炎反应。PPARα的表达在RSDS小鼠中受到抑制。然而,奥斯特孔治疗逆转了对 PPARα 表达的抑制。我们发现,在奥斯特孔处理的小鼠中,血红素加氧酶-1的表达与PPARα的表达呈正相关。总之,奥司孔有望成为治疗焦虑症的中药。在设计治疗精神疾病的新型药物时,研究人员应考虑以激活 PPARα 为目标。
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来源期刊
Neurochemistry international
Neurochemistry international 医学-神经科学
CiteScore
8.40
自引率
2.40%
发文量
128
审稿时长
37 days
期刊介绍: Neurochemistry International is devoted to the rapid publication of outstanding original articles and timely reviews in neurochemistry. Manuscripts on a broad range of topics will be considered, including molecular and cellular neurochemistry, neuropharmacology and genetic aspects of CNS function, neuroimmunology, metabolism as well as the neurochemistry of neurological and psychiatric disorders of the CNS.
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