Network pharmacology combined with metabolomics to investigate the anti-hyperlipidemia mechanism of a novel combination

[Display omitted] •Lindera aggregate leaves and Aloe barborescens are both new food resources and traditional medicine.•Aqueous extract of Lindera aggregate and Aloe barborescens alleviated hyperlipidemia.•Network pharmacology coupled with Metabolomics decipher the multi-target mechanisms.•Differential expressions of CYP7A1, ACAT and HMGCR contribute to the hypolipidemic mechanism of AqLL-A. This study aimed to investigate the hypolipidemic effect and mechanism of aqueous extract of Lindera aggregate leaves and Aloe vera (AqLL-A) in mice. Chemical profile of AqLL-A, serum/hepatic lipid profiles, and fecal TG were measured. The major components of AqLL-A related to hyperlipidemia, quercitrin and aloin were confirmed by HPLC. AqLL-A reduced serum/hepatic lipids, while elevated serum HDL, APOA1, fecal TG levels in hyperlipidemia mice. Furthermore, 20 potential biomarkers were detected by UPLC-QTOF/MS, and all of them were approached to a normal-like level after treatment of AqLL-A. Network pharmacology combined with metabolomics elucidate the related pathways involved in hyperlipidemia. The experimental validation indicated the differential expressions of CYP7A1, ACAT and HMGCR contribute to the hypolipidemic mechanism of AqLL-A. These results suggested that AqLL-A alleviated hyperlipidemia effectively, it might play synergistic therapeutic efficacies through regulating metabolic profiles and related signaling pathway.