The hot water extraction of polysaccharides from the fruiting body of Pleurotus eryngii was studied. In this paper, according to single-factor experiments, a response surface methodology and the Box-Behnken design were applied to optimize the extraction parameters of Pleurotus eryngii polysaccharides (PEP). The optimal extraction conditions were as follows: a temperature of 79 °C, a time of 3.11 h, a ratio of water to fruiting bodies of 52.6 mL g-1. Under these parameters, the yield of PEP was 7.53%. When mice with hyperlipidemia were administered low, medium or high doses of PEP, their body weight was reduced compared with the model group, and the degree of weight loss was proportional to the dose. At the 16th week of PEP treatment, blood lipid biochemical parameters such as total cholesterol, triglycerides, low-density lipoprotein-cholesterol, aspartate aminotransferase, and alanine aminotransferase levels were all decreased. However, high-density lipoprotein-cholesterol levels increased after PEP treatment. Histopathological examination of the liver showed that low, medium and high doses of PEP had a certain liver protective effect. High-dose PEP treatment had the best effect in regard to lipid-lowering and liver protection. In addition, the metabolome of the mice was analyzed by LC-MS, and the results indicated that C16 sphinganine can be used as a potential biomarker, which displayed significant differences among the six groups. In conclusion, the possible metabolic mechanism of the PEP on lipid-lowering was closely related to sphingolipid metabolism.
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