Apigenin for Depression and Anxiety: A Systematic Review of Preclinical Studies

Depression and anxiety are debilitating disorders with complex pathophysiologies associated with neurotransmitter deficits, neuroinflammation, and oxidative stress. Apigenin, a dietary flavonoid, has therapeutic potential because of its neuroprotective properties.

We assessed the antidepressant and anxiolytic effects of apigenin in rodent models, focusing on behavioral outcomes, mechanisms involving neuroinflammation, oxidative stress, and neurotransmitter balance, and relevant molecular pathways. A systematic search of PubMed, Scopus, and Embase was conducted through July 2025. In vivo rodent studies evaluating the effects of apigenin on depression or anxiety were included. Exclusion criteria comprised studies addressing other disorders, apigenin derivatives, or non-original research. Data on study design, model, treatment, outcomes, and mechanisms were extracted.

Of 953 screened records, 21 studies met the inclusion criteria. Preclinical evidence consistently indicated that apigenin ameliorated depressive- and anxiety-like behaviors across diverse rodent models, frequently demonstrating effects comparable to or greater than those of conventional pharmacological treatments. Mechanistically, apigenin mediated its neuropsychological effects through multiple pathways, including reducing oxidative and nitrosative stress, inhibiting neuroinflammation, modulating monoaminergic neurotransmission, upregulating neurotrophic factors such as brain-derived neurotrophic factor (BDNF) and cAMP response element-binding protein (CREB), and regulating energy metabolism and neurogenesis. Apigenin exhibited a favorable safety profile across all included studies, even at high doses.

In rodent models, apigenin exhibits substantial antidepressant and anxiolytic effects through complex mechanisms involving redox modulation, anti-inflammatory activity, neurotransmitter regulation, and neurotrophic support. These findings indicate that apigenin warrants further translational investigation and potential therapeutic development for treating depression and anxiety disorders.