Yanghuo Sanqi capsule against Alzheimer's disease by upregulating lipid metabolism: Network pharmacology and multi-omics analysis

Yanghuo Sanqi capsule (YSC) consists of Yingyanghuo (Epimedium brevicornu Maxim., YYH) and Sanqi (Panax notoginseng (Burk.) F.H.Chen, SQ), which is used to treat cardiovascular diseases in Traditional Chinese Medicine (TCM). Additionally, the accumulated evidence suggests that it has the potential to treat Alzheimer's disease (AD). This study tries to elucidate the mechanisms of YSC against AD by combining network pharmacology of absorbed components with multi-omics of Caenorhabditis elegans (C. elegans). Firstly, network pharmacology was used to predict the target of the YSC in the treatment of AD. Then, Caenorhabditis elegans (C. elegans) CL4176 and CL2355 were used to study the effect of YSC on AD, and the mechanism was studied through multi-omics. Finally, potential therapeutic targets and bioactivity ingredients were identified through validation experiments, molecular docking, and molecular dynamics simulation. The network pharmacology of 15 mice blood components suggested that YSC may intervene in AD by regulating lipid metabolism and amyloid precursor protein (APP). In addition, YSC can alleviate Aβ-induced toxicity in both muscle and nerve in C. elegans. Transcriptomic and metabolomic analysis in C. elegans showed that YSC protected against AD by increasing lipid metabolism, which can maintain lipid homeostasis inside and outside the cell and down-regulating APP to alleviate Aβ-induced toxicity. Anhydroicaritin (AHI) is an important bioactive ingredient involved in regulating APP error clipping and lipid metabolism in YSC. This study reveals the mechanism of YSC anti-AD and provides experimental support for expanding its clinical use.