Polygonum perfoliatum L. has a long history of medicinal and edible applications. Studies have shown that it can significantly protect liver injury, but the mechanism is unclear. The purpose of this study was to explore the protective mechanism of P. perfoliatum on chronic alcoholic liver injury from the perspective of lipid metabolism. After 8 weeks of alcohol exposure in male Wister mice, the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) in serum were significantly increased, and the activities of alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) in liver were significantly decreased. Meanwhile, pathological changes of liver tissue in mice were observed by histopathology. Then, Ultra-High Performance Liquid Chromatography (UHPLC) QExactive Plus Mass Spectrometer lipidomics and matrix-assisted laser desorption/ionization time-of-flight/time -of-flight (MALDI-TOF/TOF) mass spectrometry imaging methods were established to analyze lipid metabolism in mice. Ten different lipids were identified by statistical analysis, including Fatty Acyls, Glycerophospholipids, Prenol lipids and Sphingomyelins. After intervention with P. perfoliatum extracts at different doses (25 to 100 mg/kg), levels of AST, ALT, ALP in serum, and activities of ADH and ALDH in liver were significantly corrected. The hepatic cord structure was clear, and the liver cells were closely arranged without other obvious abnormalities. Non-target lipidomics analysis showed that P. perfoliatum extract could regulate the metabolic disorders of the 10 different lipids caused by continuous alcohol exposure. Pathway analysis suggested that the mechanism of P. perfoliatum extract on chronic alcoholic liver injury may be related to the regulation of linoleic acid and α-linolenic acid.

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