Data mining and multi-omics profiling to reveal the mechanisms of cold/hot property of traditional Chinese medicine in Alzheimer’s disease treatment

Alzheimer’s disease (AD) is a severely debilitating condition that significantly hampers independent living, with no effective treatments currently available. Traditional Chinese medicine (TCM) has shown substantial promise in both preventing and alleviating AD symptoms. The medicinal properties—specifically hot, warm, cool, and cold—serve as a critical link between TCM theory and clinical application. However, the majority of research has concentrated on individual herbs for AD, with relatively few comprehensive studies exploring the biological mechanisms through which these herbs exert their medicinal properties. In this context, data mining, network pharmacology, and multi-omics approaches, including metabolomics, gut microbiota analysis, and proteomics, were employed to elucidate the effects and mechanisms of action of three hot/warm property herbs (THPH) and three cold/cool property herbs (TCPH) in the treatment of AD. Findings indicated that the herbs effective against AD primarily possess warm properties. THPH demonstrated a significant enhancement in cognitive, learning, and memory functions in AD rat models when compared to TCPH, potentially achieving therapeutic effects by boosting the synthesis of the neurotransmitter acetylcholine. Furthermore, THPH modulated energy metabolism, corrected metabolic imbalances in both brain and serum within AD rat models, inhibited oxidative stress, restored synaptic plasticity-related proteins and signaling pathways, and maintained intestinal microbiota homeostasis. Consequently, this study offers valuable insights into the therapeutic implications of the hot (warm) and cold (cool) properties of TCM in the management of Alzheimer’s disease.