Guanlin Xiao,1 Guangying Wu,2 Yanchang Liu,2 Wanchun Chen,2 Zhihao Zeng,2 Sumei Li,1 Yangxue Li,1 Xiaoli Bi1 

1Guangdong Provincial Engineering Technology Research Institute of Traditional Chinese Medicine/Guangdong Provincial Key Laboratory of Research and Development in Traditional Chinese Medicine, Guangzhou, People’s Republic of China; 2School of the Fifth Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China

Correspondence: Guanlin Xiao, Email 164669079@qq.com Xiaoli Bi, Email zyfxyjs@gzucm.edu.cn

Background: Microctis Folium (MF), a traditional Chinese medicine (TCM), has shown promising effects in treating hyperlipidemia (HLP), yet its active constituents and mechanisms remain largely unclear.
Purpose: This study aimed to systematically elucidate the lipid-lowering effects of MF on high-fat diet (HFD)-induced HLP and identify its pharmacodynamic material basis and molecular mechanism through an integrated multi-omics strategy.
Methods: We developed a UPLC-QTOF-MS/MS method to identify the chemical constituents of MF and the compounds absorbed in rat serum after oral administration of MF. Network pharmacology, molecular docking, and experimental validation were utilized to explore the potential mechanism of MF for the treatment of HLP.
Results: UPLC-QTOF-MS/MS identified 51 chemical compounds in MF and established their material basis. Analysis of serum samples after administration of MF identified 24 enriched compounds as potential active compounds and 597 corresponding prospective targets. Overlaying these compounds with 396 HLP-related genes revealed 101 potential core genes, mainly including AKT1, PTGS2, EGFR, mTOR, and NF-κB. Network pharmacology and transcriptomic analyses indicated that MF regulates key pathways in HLP, notably the PI3K/AKT, mTOR, and NF-κB pathways. Molecular docking further validated the binding affinities of MF key compounds (rutin and isovitexin) to AKT1, mTOR, and NF-κB. In vivo studies confirmed MF’s lipid-lowering effects of MF in alleviating HFD-induced lipid accumulation. Compared to the HFD group, MF treatment significantly reduced serum triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels while increasing high-density lipoprotein cholesterol (HDL-C) levels. Finally, in vivo experiments confirmed the pivotal role of these pathways in the therapeutic effects of MF on HLP.
Conclusion: The comprehensive approach adopted in this study reveals the molecular mechanism of MF for the treatment of HFD-induced HLP, lays an important foundation for elucidating the pharmacological and material basis of the therapeutic effects of MF, and highlights the value of multi-omics integration in TCM research.

Keywords: Pothos chinensis (Raf.) Merr, hyperlipidemia, network pharmacology, serum pharmacochemistry, transcriptomics