Integrated analysis of metabolomic and transcriptomic profiling reveals the effect of Atractylodes oil on Spleen Yang Deficiency Syndrome in rats

Ethnopharmacological relevance: Spleen Yang Deficiency Syndrome (SYDS), which is a syndrome commonly treated with Traditional Chinese Medicine (TCM), manifests as overall metabolic dysfunction caused mainly by digestive system disorders. Atractylodes lancea (Thunb.) DC. (AL) is a widely used traditional herb with the efficacy of eliminate dampness and strengthen the spleen, Atractylodes oil (AO) is a medicinal component of AL and can be used to treat various gastrointestinal disorders. However, its effects on SYDS and underlying mechanisms have not been clarified to date.Aim of the study: The present study aimed to investigate the efficacy of AO in the improvement of the symptoms of SYDS in rat and the underlying mechanism by integrating transcriptomics, and metabolomics.Materials and methods: The SYDS rats induced by reserpine were treated with AO. The protective effect of AO on SYDS rats was evaluated by serum biochemical detection, histopathological analyses. Enzyme-linked immunosorbent assay (ELISA), colorimetric assay and immunofluorescence (IF) were performed to determine the levels of relevant indicators of mitochondrial function and energy metabolism in the liver. Liver metabolites and transcript levels were assessed by non-targeted metabolomics and transcriptomics to analyze potential molecular mechanisms and targets. The expression of the corresponding proteins was verified using Western blotting. Results: AO not only regulated the digestion, absorption function and oxidative stress status of SYDS rats, but also improved mitochondrial function and alleviated energy metabolism disorders in SYDS rats. Metabolomic and transcriptomic analyses demonstrated that AO regulation is mainly exerted in amino acid metabolism, unsaturated fatty acid metabolism, TCA cycle as well as PPAR and AMPK signaling pathways. In addition, The AMPK signaling pathway was verified and AO promoted AMPK phosphorylation and the expression of SIRT1, PGC-1 alpha, and PPAR alpha in SYDS rats.Conclusions: The therapeutic effect of AO on SYDS is potentially attributable to activation of the AMPK/SIRT1/ PGC-1 alpha signaling pathway, which enhances transport and regulation of energy metabolism.