TY - JOUR PY - 2023// TI - Ononin ameliorates depression-like behaviors by regulating BDNF-TrkB-CREB signaling in vitro and in vivo JO - Journal of ethnopharmacology A1 - Gong, Guowei A1 - Ganesan, Kumar A1 - Wang, Yongjie A1 - Zhang, Zhenxia A1 - Liu, Yaqun A1 - Wang, Junli A1 - Yang, Fenglian A1 - Zheng, Yuzhong SP - ePub EP - ePub VL - ePub IS - ePub N2 - ETHNOPHARMACOLOGICAL RELEVANCE: 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.

AIM OF THE STUDY: 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.

MATERIALS AND METHODS: 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.

RESULTS: 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.

CONCLUSION: Based on these findings, we suggest that ononin is a promising antidepressant candidate for treating depression.

Language: en

LA - en SN - 0378-8741 UR - http://dx.doi.org/10.1016/j.jep.2023.117375 ID - ref1 ER -