As a disorder of lipid metabolism, hyperlipidemia (HLP) is characterized by elevated levels of lipids in the blood circulation. It is consistently related to the development of cardiovascular events and diseases associated with metabolic syndrome. Alismatis Rhizoma decoction (ARD), a well-known traditional Chinese medicine prescription, has long been used for treating vertigo, which is a symptom experienced by HLP patients. In this study, we aimed to investigate the hyperlipidemic activity and the potential molecular mechanisms of ARD in HLP rats at the transcriptional level. RNA sequencing and transcriptome analysis were performed collaboratively, including analysis of differentially expressed genes (DEGs), GO functions, and KEGG pathway analysis. The results showed that 1981 DEGs (1370 upregulated and 611 downregulated) were identified in the HFD group compared with the CON group. Moreover, 474 DEGs (350 upregulated and 124 downregulated) were detected in the ARD group compared with the HFD group. Furthermore, GO analysis revealed that DEGs were mainly involved in the following functions: developmental process, response to an external stimulus, ion transport, alcohol binding, and plasma membrane part. Pathway analysis suggested that these DEGs were significantly enriched in bile secretion, malaria, cell adhesion molecules, retinol metabolism, the sphingolipid signaling pathway, chemical carcinogenesis, and the T cell receptor signaling pathway. In conclusion, our study demonstrated that ARD alleviated the lipid metabolism disorder caused by HLP through multiple mechanisms, which provided vital scientific evidence for further pharmacological studies of ARD.
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