Metabolomics study of lipid lowering effect and lysophospholipids regulation by Alismatis rhizoma and processed forms in hyperlipidemia mice

Alismatis rhizoma (AR) is a traditional herb used for its lipid-regulating properties. Its processed forms, Salt-processed AR (SAR) and bran-processed AR (BAR), are widely used. This study investigates the lipid-lowering effects of AR and its processed forms in hyperlipidemic mice, with a focus on lysophospholipid regulation. Three types of serum lysophospholipids were characterized using UHPLC-QTOF-MS/MS, and their metabolic changes were analyzed with multivariate statistical statistics. The results showed that AR effectively reduced total cholesterol (TC), while SAR and BAR excelled in lowering low-density lipoprotein cholesterol (LDL-C). BAR demonstrated superior effects on the TC/high-density lipoprotein-cholesterol (HDL-C) ratio, atherogenic index (AI), and protecting kidney function, making it the most effective processed forms. Additionally, a total of 216 lysophospholipids, including 153 lysophosphatidylcholines (Lyso-PCs), 49 lysophosphatidylethanolamines (Lyso-PEs), and 14 lysophosphatidylserines (Lyso-PSs), were identified in serum samples. Metabolomics analysis revealed 102 differential lysophospholipids associated with hyperlipidemia, among which 29, 21, and 22 were significantly (VIP>1.0, P<0.05) regulated by AR, SAR, and BAR, respectively. AR showed the most comprehensive regulation of lysophospholipids, increasing unsaturated Lyso-PCs and decreasing Lyso-PEs and Lyso-PSs, which might reduce inflammation and improve cardiovascular health. This study is the first to comprehensively compare the lipid-lowering effects of AR and its processed forms, highlighting their role in modulating lysophospholipid metabolism in hyperlipidemia.