Total organic acids from Cuscuta chinensis Lam. Modulate MDM2 to promote neurogenesis and alleviate depression

作者：Ai L, Zhao Y, Zhao K, Shuang R, Hou D, Sun T, Zhao M, Tao W, Wang H · 发表于：Journal of ethnopharmacology · 年份：2026 · DOI：10.1016/j.jep.2026.122140 · 研究领域：CSDS、FOXO3、MDM2、Neurogenesis、Total organic acids from Cuscuta chinensis Lam.

ETHNOPHARMACOLOGICAL RELEVANCE: The seeds of Cuscuta chinensis Lam. (CCL) are commonly used in traditional Chinese medicine to strengthen kidney qi and alleviate mental fatigue as well as mood dysregulation and affective disturbances. Total organic acids, as major active constituents, have been reported to exert neuroprotective and mood-modulating effects, supporting their relevance to depression research. AIM OF THE STUDY: Investigating the antidepressant effects and elucidating underlying molecular mechanisms of total organic acids from Cuscuta chinensis Lam. (Ora) on neurogenesis and neural plasticity through the MDM2 (E3 ubiquitin ligase)/FOXO3 (Forkhead box O3) ubiquitination regulatory pathway. MATERIALS AND METHODS: Organic acids were extracted and isolated from Cuscuta chinensis Lam., and their major components were qualitatively identified by ultra-performance liquid chromatography coupled with LTQ-Orbitrap mass spectrometry (UPLC/LTQ-Orbitrap-MS) analysis. Subsequently, a chronic social defeat stress (CSDS) paradigm was established, and behavioral assessments were undertaken to delineate the influence of Ora in CSDS-exposed mice. Immunoblotting was used to quantify synaptic plasticity-associated proteins, and Golgi staining was subsequently applied to examine dendritic spine density. Immunofluorescence and immunohistochemistry were carried out to characterize neural stem/progenitor cell proliferation and differentiation both in vitro and in vivo, with Sholl analys...