Targeting Programmed Cell Death in Depression: A Review of Traditional Chinese Medicine Interventions Based on Preclinical Evidence

Huanhuan Jia,1 Minmin Wu,1 Lili Teng,1 Wenjing Song,1 Xinyue Li,1 Binhan Wang,1 Ying Huang,1 Xingyu Kang,1 Luwen Zhu2 1Graduate School, Heilongjiang University of Chinese Medicine, Harbin, People’s Republic of China; 2Department of Rehabilitation, The Second Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, People’s Republic of ChinaCorrespondence: Luwen Zhu, Department of Rehabilitation, The Second Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, People’s Republic of China, Email zhuluwen1983@126.comAbstract: Depression is a globally prevalent, highly disabling mental disorder, and its etiology, pathological mechanisms, and treatment approaches have long been a focus of intensive research. Programmed cell death (PCD) refers to a process in which cells actively undergo death to maintain internal homeostasis via specific signals or stimuli. Modern medical studies have demonstrated that the dysregulation of PCD modalities, including apoptosis, pyroptosis, autophagy, ferroptosis, necroptosis, and cuproptosis, is closely associated with the onset and progression of depression. Elucidating the molecular mechanisms of PCD in depression could provide critical insights for an in-depth understanding, prevention, and treatment of this disorder. In recent years, extensive research has been conducted in the field of traditional Chinese medicine (TCM) that targets PCD for depression treatment, yielding significant phased achievements. Therefore, this narrative review, covering literature primarily from the past decade, synthesizes preclinical evidence on six PCD modalities in depression. It further explores the potential mechanisms and current status of TCM interventions that target these PCD pathways, and discusses the crosstalk between them. By emphasizing mechanistic insights, this work aims to provide a theoretical foundation and guidance for future clinical prevention, treatment, and research on depression.Keywords: depression, programmed cell death, traditional Chinese medicine