Shenling Baizhu San (SLBZS), a famous
traditional Chinese medicine, has been demonstrated to exert protective effects against
non-alcoholic fatty liver disease (
NAFLD), but its exact mechanisms have not been well understood. The aim of this study was to investigate the mechanisms underlying the protective effects of SLBZS in a rat model of
NAFLD using lipidomics and to evaluate the role of
Sirtuin 1 (
SIRT1) in the mechanism of SLBZS against
NAFLD. The rat model of
NAFLD was induced by high-fat feeding. An ultra-performance liquid chromatography-mass spectrometry (UHPLC-MS)-based untargeted lipidomics approach was applied to analyze hepatic
lipid alterations, and the SIRT1-selective inhibitor
EX 527 was used to inhibit
SIRT expression in the liver. The results of body and biochemical parameters, as well as histological changes, indicated that SLBZS administration exerted protective effects against
NAFLD. Lipidomic analysis showed that 30
lipid species were effectively regulated by SLBZS administration in rats fed a high-fat diet. Pathway analysis indicated that
glycerophospholipid metabolism and glycerolipid metabolism were potential target pathways closely involved in the mechanism of SLBZS against
NAFLD. Moreover, the beneficial effects of SLBZS on hepatic steatosis, some biochemical parameters and hepatic
lipid species were partly diminished by
SIRT1 inhibition. In conclusion, our results suggested that SLBZS administration could effectively alter some hepatic
lipid species in rats fed a high-fat diet, which was mainly associated with the regulation of
glycerophospholipid and glycerolipid metabolism. Furthermore, the beneficial effects of SLBZS on hepatic lipid metabolism may be at least partly attributed to
SIRT1 activation in the liver.