Post-stroke depression update 2025: Mechanisms, prediction, and management

Table 2 Pharmacological mechanisms of selected traditional Chinese medicine formulations in post-stroke depression

Prescription/preparation	Active ingredients	Mechanism of action	Level of evidence (oxford)1	GRADE quality of evidence2	Ref.
Shuyu capsules relieve liver	Adhyperforin, etc.	Reversing the disruptions of the p-ERK, p-CREB and BDNF	5	Not applicable (pre-clinical)	[103]
Chaihu Shugan powder	Seven Chinese herbs including bupleurum	Chaihu-Shugan-San inhibits neuroinflammation in the treatment of post-stroke depression through the JAK/STAT3-GSK3β/PTEN/Akt pathway	5	Not Applicable (pre-clinical)	[50,105]
Danzhi Xiaoyao San	Eight Chinese herbs including Paeoniae Radix Alba	Reducing neuroinflammation through PKCγ/p38/NF-κB signaling pathway	5	Not applicable (pre-clinical)	[106,107]
Jiao-tai-wan (JTW)	Jatrorrhizine	JTW could exert antidepressant effects by modulating neuroinflammation via inhibition of the STING pathway	5	Not applicable (pre-clinical)	[108]
Flavones	Apigenin, etc.	Flavones exert protective effects against depression in mice, primarily by stimulating neurotrophic factors and modulating inflammatory pathways	5	Not applicable (pre-clinical)	[109]
Dendrobium officinale	Dendrobine (DEN) and erianin (ERI)	DEN and ERI alleviated LPS-induced microglial activation and neuroinflammation by binding to PDE4B and preventing TLR4/NF-κB signaling pathway	5	Not applicable (pre-clinical)	[110]
Corydalisyanhusuopolysaccharides (CYP)	CYP	Corydalis yanhusuo polysaccharides regulates HPA-axis mediated microglia activation and inhibits astrocyte A1 transformation to improve depression-like behavior	5	Not applicable (pre-clinical)	[111]

¹Oxford Centre for Evidence-Based Medicine 2011 levels of evidence: Level 5 refers to mechanism-based reasoning or expert opinion, which encompasses findings from experimental/mechanistic studies that form the basis for future clinical research.

²GRADE assessment: The evidence summarized in this table is derived from preclinical studies elucidating potential mechanisms of action. As such, it is classified as mechanistic exploration and a formal GRADE rating (high, moderate, low, very low) is not applicable (N/A). This evidence is crucial for understanding biological plausibility but requires validation in human clinical trials before any conclusions regarding clinical efficacy can be drawn.

HPA: Hypothalamic-pituitary-adrenal; LPS: Lipopolysaccharide.