Epitranscriptomic and immunometabolic mechanisms of traditional Chinese medicine in metabolic-associated cognitive impairment: a narrative review.

Metabolic-associated cognitive impairment (MACI) is a major complication of metabolic disorders such as obesity, type 2 diabetes mellitus (T2DM), and metabolic dysfunction-associated steatotic liver disease (MASLD). It manifests as impairments in learning, memory, and executive function, with pathogenesis involving insulin resistance, chronic low-grade inflammation, immune–metabolic imbalance, synaptic plasticity deficits, and aberrant epitranscriptomic regulation. In recent years, traditional Chinese medicine (TCM), with its multi-component and multi-target characteristics, has demonstrated unique advantages in preventing and treating MACI. Emerging evidence indicates that TCM can modulate RNA modifications (e.g., m6A), improve immune–metabolic homeostasis, suppress neuroinflammation, and restore synaptic plasticity to enhance cognitive function. This review summarizes the pathological mechanisms of MACI, highlights recent advances in understanding how TCM exerts therapeutic effects through epitranscriptomic and immunometabolic pathways, and discusses the application of network pharmacology, multi-omics, and spatial transcriptomics in elucidating TCM mechanisms. Finally, we address challenges and future directions for the clinical translation of TCM, emphasizing that integration of multi-omics approaches and precision medicine strategies may facilitate innovative applications of TCM in MACI management.