Ononin 是一种黄酮类化合物，存在于多种药用植物中，包括黄芪、苦参和刺槐。这些植物传统上因其药用特性而在世界各地使用，包括抗炎、抗氧化和抗肿瘤作用。重度抑郁症是一种常见、持久、反复发作的精神疾病，自杀率很高。天然存在的黄酮类化合物通过知之甚少的机制治疗抑郁症。本研究旨在确定 ononin 是否在 PC12 细胞模型和慢性轻度应激 (CMS) 诱导的抑郁大鼠模型中赋予抗抑郁样作用，并探讨其可能的机制。使用蔗糖偏好、尾部悬挂和旷场测试来测量行为。此外，为了探索这些机制，我们采用了体外和体内测定方法，包括神经突生长、蛋白质印迹、定量RT-PCR和染色方法。Ononin或BDNF处理显着增加了PC12细胞的神经元生长和分化。此外，Ononin 还能促进 TrkB 和生长因子的激活，并上调 PI3K/Akt 和 BDNF/TrkB/CREB ​​信号通路。体外结果与 CMS 诱导的抑郁大鼠模型一致，其中 Ononin 治疗显着减少抑郁样行为，并激活额叶皮层和海马中的 TrkB、生长因子和 BDNF/TrkB/CREB ​​信号通路。 CMS 引起的抑郁症大鼠的额叶皮层和海马体中由抑郁引起的微观变化在 ononin 治疗后也得到减轻。基于这些发现，我们认为 ononin 是治疗抑郁症的一种有前景的抗抑郁候选药物。版权所有 © 2023。由 Elsevier 出版B.V.

Ononin is a flavonoid compound found in several medicinal plants, including Astragalus membranaceus, Sophora flavescens, and Ononis spinosa. These plants have been traditionally used in various parts of the world for their medicinal properties, including anti-inflammatory, antioxidant, and antitumor effects. Major depression is a common, long-lasting, and recurrent psychiatric disorder with a high suicide rate. Naturally occurring flavonoids treat depression via poorly understood mechanisms.The present study aimed to determine whether ononin conferred an antidepressant-like effect in PC12 cell models and chronic mild stress (CMS)-induced depressive rat models and to explore its possible mechanisms.Depression-related behaviors were measured using sucrose preference, tail suspension and open-field tests. Furthermore, to explore these mechanisms, we employed in vitro and in vivo assay methods, including neurite outgrowth, western blotting, quantitative RT-PCR, and staining methods.Treatment with ononin or BDNF significantly increased PC12 cells' neuronal growth and differentiation. Furthermore, ononin promotes the activation of TrkB and growth factors and upregulates the PI3K/Akt and BDNF/TrkB/CREB signaling pathways. The in vitro results were consistent with CMS-induced depressive rat models, in which ononin treatment significantly decreased depression-like behaviors and activated TrkB, growth factors, and BDNF/TrkB/CREB signaling pathways in the frontal cortex and hippocampus. Depression-induced microscopic alterations in the frontal cortex and hippocampus of rats with CMS-induced depression were also mitigated following ononin treatment.Based on these findings, we suggest that ononin is a promising antidepressant candidate for treating depression.Copyright © 2023. Published by Elsevier B.V.