[Regulatory effect of Diwu Yanggan Decoction on lysoglycerophospholipids in circulating exosomes in a mouse model of nonalcoholic fatty liver disease].

Objective: To evaluate the regulatory effect of Diwu Yanggan (DWYG) Decoction on lysoglycerophospholipids (Lyso-GPLs) in circulating exosomes in a mouse model of nonalcoholic fatty liver disease (NAFLD).

Methods: Circulating exosomes isolated from mouse serum by size exclusion chromatography were morphologically characterized using transmission electron microscope and examined for surface markers CD9, CD63 and TSG101 using Western blotting. Twenty-four male Kunming mice were randomized into 3 groups for normal feeding (control, n=8) or high-fat diet feeding for 1 week to induce NAFLD, after which the latter mice were given DWYG decoction (treatment group, n=8) or normal saline (model group, n=8) by gavage for 4 weeks. After the last treatment, blood samples were collected from the mice for testing serum TC, HDL-C, LDL-C, ALT and AST levels and isolating circulating exosomes. Using multivariate statistical analysis based on targeted metabolomics strategy, the potential biomarkers for Lyso-GPLs in the exosomes were screened.

Results: The isolated exosomes about 100 nm in size had a typical saucer-like structure with distinct double-layer membranes and a mean particle size of 137.5 nm and expressed the specific surface marker proteins CD9, CD63 and TSG101. The mouse models of NAFLD had significantly increased serum levels of TC, HDL-C, LDL-C and AST and lowered serum ALT level. A total of 43 Lyso-GPLs with significant reduction after DWYG Decoction treatment were identified in NAFLD mice.

Conclusion: DWYG Decoction can regulate Lyso-GPLs in circulating exosomes in NAFLD mice, which provides a new clue for studying the therapeutic mechanism of DWYG Decoction for liver disease.